Scientific Output

Over 10.000 scientific papers have been published by members of the Materials Chain since the foundation of the University Alliance Ruhr in 2010. This tremendous output is proof of the excellent environment the Ruhr Area provides for research in the field of materials science and technology.

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  • 2020 • 520 Standard Gibbs energy of metabolic reactions: V. Enolase reaction
    Greinert, T. and Vogel, K. and Seifert, A.I. and Siewert, R. and Andreeva, I.V. and Verevkin, S.P. and Maskow, T. and Sadowski, G. and Held, C.
    Biochimica et Biophysica Acta - Proteins and Proteomics 1868 (2020)
    The glycolytic pathway is one of the most important pathways for living organisms, due to its role in energy production and as supplier of precursors for biosynthesis in living cells. This work focuses on determination of the standard Gibbs energy of reaction ΔRg′0 of the enolase reaction, the ninth reaction in the glycolysis pathway. Exact ΔRg′0 values are required to predict the thermodynamic feasibility of single metabolic reactions or even of metabolic reaction sequences under cytosolic conditions. So-called “apparent” standard data from literature are only valid at specific conditions. Nevertheless, such data are often used in pathway analyses, which might lead to misinterpretation of the results. In this work, equilibrium measurements were combined with activity coefficients in order to obtain new standard values ΔRg′0 for the enolase reaction that are independent of the cytosolic conditions. Reaction equilibria were measured at different initial substrate concentrations and temperatures of 298.15 K, 305.15 K and 310.15 K at pH 7. The activity coefficients were predicted using the equation of state electrolyte Perturbed-Chain Statistical Associating Fluid Theory (ePC-SAFT). The ePC-SAFT parameters were taken from literature or fitted to new experimentally determined osmotic coefficients and densities. At 298.15 K and pH 7, a ΔRg′0(298.15 K, pH 7) value of −2.8 ± 0.2 kJ mol− 1 was obtained. This value differs by up to 5 kJ mol− 1 from literature data. Reasons are the poorly defined “standard” conditions and partly undefined reaction conditions of literature works. Finally, using temperature-dependent equilibrium constants and the van ‘t Hoff equation, the standard enthalpy of reaction of ΔRh′0(298.15 K, pH 7) = 27 ± 10 kJ mol− 1 was determined, and a similar value was found by quantum-chemistry calculations. © 2020 Elsevier B.V.
    view abstractdoi: 10.1016/j.bbapap.2020.140365
  • 2020 • 519 Standard Gibbs energy of metabolic reactions: IV. Triosephosphate isomerase reaction
    Greinert, T. and Baumhove, K. and Sadowski, G. and Held, C.
    Biophysical Chemistry 258 (2020)
    The glycolytic pathway is present in most organisms and represents a central part of the energy production mechanism in a cell. For a general understanding of glycolysis, the investigation from a thermodynamic point of view is essential and allows realising thermodynamic feasibility analyses under in vivo conditions. However, available literature standard Gibbs energies of reaction, ΔRg′0, are calculated using equilibrium-molality ratios Km′, which might lead to a misinterpretation of the glycolytic pathway. It was the aim of this work to thermodynamically investigate the triosephosphate isomerase (TPI) reaction to provide new activity-based reaction data. In vitro equilibrium experiments were performed, and activity coefficients were predicted with the equation of state electrolyte PC-SAFT (ePC-SAFT). The combination of experimental concentrations and predicted activity coefficients yielded the thermodynamic equilibrium constant Ka and a new value for ΔRg′0(298.15 K, pH 7) = 7.1 ± 0.3 kJ mol‑1. The availability of the new ΔRg′0 value allowed predicting influences of the reaction medium on the reaction equilibrium of the TPI reaction. In this work, influences of the initial substrate concentration, pH and Mg2+ concentration on the reaction equilibrium were investigated and a method is presented to predict these influences. The higher the substrate concentration and the higher the temperature, the stronger the reaction equilibrium is shifted on the product side. While the pH did not have a significant influence on the reaction equilibrium, Mg2+ yielded a shift of the reaction equilibrium to the substrate side. All these effects were predicted correctly with ePC-SAFT. Based on the ePC-SAFT predictions we concluded that a charge-reduction of the product by complexation of the product with Mg2+ was responsible for the strong influence of Mg2+ on the reaction equilibrium. Finally, the standard enthalpy of reaction of ΔRh′0(pH 7) = 18 ± 7 kJ mol‑1 was determined with the equilibrium constants Ka at 298.15 K, 304.15 K and 310.15 K using the van ‘t Hoff equation. © 2020 Elsevier B.V.
    view abstractdoi: 10.1016/j.bpc.2020.106330
  • 2020 • 518 Herpesviruses induce aggregation and selective autophagy of host signalling proteins NEMO and RIPK1 as an immune-evasion mechanism
    Muscolino, E. and Schmitz, R. and Loroch, S. and Caragliano, E. and Schneider, C. and Rizzato, M. and Kim, Y.-H. and Krause, E. and Juranić Lisnić, V. and Sickmann, A. and Reimer, R. and Ostermann, E. and Brune, W.
    Nature Microbiology 5 331-342 (2020)
    Viruses manipulate cellular signalling by inducing the degradation of crucial signal transducers, usually via the ubiquitin–proteasome pathway. Here, we show that the murine cytomegalovirus (Murid herpesvirus 1) M45 protein induces the degradation of two cellular signalling proteins, the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) essential modulator (NEMO) and the receptor-interacting protein kinase 1 (RIPK1), via a different mechanism: it induces their sequestration as insoluble protein aggregates and subsequently facilitates their degradation by autophagy. Aggregation of target proteins requires a distinct sequence motif in M45, which we termed ‘induced protein aggregation motif’. In a second step, M45 recruits the retromer component vacuolar protein sorting 26B (VPS26B) and the microtubule-associated protein light chain 3 (LC3)-interacting adaptor protein TBC1D5 to facilitate degradation of aggregates by selective autophagy. The induced protein aggregation motif is conserved in M45-homologous proteins of several human herpesviruses, including herpes simplex virus, Epstein–Barr virus and Kaposi’s sarcoma-associated herpesvirus, but is only partially conserved in the human cytomegalovirus UL45 protein. We further show that the HSV-1 ICP6 protein induces RIPK1 aggregation and degradation in a similar fashion to M45. These data suggest that induced protein aggregation combined with selective autophagy of aggregates (aggrephagy) represents a conserved viral immune-evasion mechanism. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.
    view abstractdoi: 10.1038/s41564-019-0624-1
  • 2020 • 517 Structure Defines Function: Clinically Relevant Mutations in ErbB Kinases
    Niggenaber, J. and Hardick, J. and Lategahn, J. and Rauh, D.
    Journal of Medicinal Chemistry 63 40-51 (2020)
    The ErbB receptor tyrosine kinase family members EGFR (epidermal growth factor receptor) and Her2 are among the prominent mutated oncogenic drivers of non-small cell lung cancer (NSCLC). Their importance in proliferation, apoptosis, and cell death ultimately renders them hot targets in cancer therapy. Small-molecule tyrosine kinase inhibitors seem well suited to be tailor-made therapeutics for EGFR mutant NSCLC; however, drug resistance mutations limit their success. Against this background, the elucidation and visualization of the three-dimensional structure of cancer-related kinases provide valuable insights into their molecular functions. This field has undergone a revolution because X-ray crystal structure determinations aided structure-based drug design approaches and clarified the effect of activating and resistance-conferring mutations. Here, we present an overview of important mutations affecting EGFR and Her2 and highlight their influence on the kinase domain conformations and active site accessibility. © 2019 American Chemical Society.
    view abstractdoi: 10.1021/acs.jmedchem.9b00964
  • 2020 • 516 Pressure-dependent electronic structure calculations using integral equation-based solvation models
    Pongratz, T. and Kibies, P. and Eberlein, L. and Tielker, N. and Hölzl, C. and Imoto, S. and Beck Erlach, M. and Kurrmann, S. and Schummel, P.H. and Hofmann, M. and Reiser, O. and Winter, R. and Kremer, W. and Kalbitzer, H.R. and...
    Biophysical Chemistry 257 (2020)
    Recent methodological progress in quantum-chemical calculations using the “embedded cluster reference interaction site model” (EC-RISM) integral equation theory is reviewed in the context of applying it as a solvation model for calculating pressure-dependent thermodynamic and spectroscopic properties of molecules immersed in water. The methodology is based on self-consistent calculations of electronic and solvation structure around dissolved molecules where pressure enters the equations via an appropriately chosen solvent response function and the pure solvent density. Besides specification of a dispersion-repulsion force field for solute-solvent interactions, the EC-RISM approach derives the electrostatic interaction contributions directly from the wave function. We further develop and apply the method to a variety of benchmark cases for which computational or experimental reference data are either available in the literature or are generated specifically for this purpose in this work. Starting with an enhancement to predict hydration free energies at non-ambient pressures, which is the basis for pressure-dependent molecular population estimation, we demonstrate the performance on the calculation of the autoionization constant of water. Spectroscopic problems are addressed by studying the biologically relevant small osmolyte TMAO (trimethylamine N-oxide). Pressure-dependent NMR shifts are predicted and compared to experiments taking into account proper computational referencing methods that extend earlier work. The experimentally observed IR blue-shifts of certain vibrational bands of TMAO as well as of the cyanide anion are reproduced by novel methodology that allows for weighing equilibrium and non-equilibrium solvent relaxation effects. Taken together, the model systems investigated allow for an assessment of the reliability of the EC-RISM approach for studying pressure-dependent biophysical processes. © 2019 Elsevier B.V.
    view abstractdoi: 10.1016/j.bpc.2019.106258
  • 2020 • 515 Synthesis of Novel Sulfobetaine Polymers with Differing Dipole Orientations in Their Side Chains, and Their Effects on the Antifouling Properties
    Schönemann, E. and Koc, J. and Aldred, N. and Clare, A.S. and Laschewsky, A. and Rosenhahn, A. and Wischerhoff, E.
    Macromolecular Rapid Communications 41 (2020)
    The impact of the orientation of zwitterionic groups, with respect to the polymer backbone, on the antifouling performance of thin hydrogel films made of polyzwitterions is explored. In an extension of the recent discussion about differences in the behavior of polymeric phosphatidylcholines and choline phosphates, a quasi-isomeric set of three poly(sulfobetaine methacrylate)s is designed for this purpose. The design is based on the established monomer 3-[N-2-(methacryloyloxy)ethyl-N,N-dimethyl]ammonio-propane-1-sulfonate and two novel sulfobetaine methacrylates, in which the positions of the cationic and the ionic groups relative to the polymerizable group, and thus also to the polymer backbone, are altered. The effect of the varied segmental dipole orientation on their water solubility, wetting behavior by water, and fouling resistance is compared. As model systems, the adsorption of the model proteins bovine serum albumin (BSA), fibrinogen, and lysozyme onto films of the various polyzwitterion surfaces is studied, as well as the settlement of a diatom (Navicula perminuta) and barnacle cyprids (Balanus improvisus) as representatives of typical marine fouling communities. The results demonstrate the important role of the zwitterionic group's orientation on the polymer behavior and fouling resistance. © 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/marc.201900447
  • 2020 • 514 Effect of water leaching on biochar properties and its impact on organic contaminant sorption
    Schreiter, I.J. and Schmidt, W. and Kumar, A. and Graber, E.R. and Schüth, C.
    Environmental Science and Pollution Research 27 691-703 (2020)
    When biochar (BC) is applied to soil, one process that can alter its properties and contaminant sorption is the leaching of minerals and dissolved organic carbon (DOC). This study investigated changes in properties of three BCs (cattle manure, grain husk, and wood chips), due to leaching, and the subsequent impact on sorption of trichloroethylene (TCE) and tetrachloroethylene (PCE). The manure-derived BC released 27.4 mg g−1 DOC, which is over ten times more than that measured for the two plant-based BCs (2.5 and 1.5 mg g−1 DOC for grain husk and wood chips, respectively). In all leachates, potassium is the dominant cation, whereas chloride, sulfate, and phosphate are the main anions. In total, the manure-derived biochar released the highest sum of total ions (73.1 mg g−1), followed by BC produced from grain husk (15.5 mg g−1) and wood chips (1.2 mg g−1). Leaching increased external surface area, mesopore volume, and hydrophobicity of the manure-derived BC and decreased its polarity. This enhanced sorption via partitioning. In plant-based BCs, micropore volume and size distribution were altered, most likely through the un-blocking of pores, causing increased sorption via pore-filling for both TCE and PCE. The results indicate that, depending on feedstock material, BC leaching can alter the environmental fate of organic compounds. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
    view abstractdoi: 10.1007/s11356-019-06904-2
  • 2019 • 513 Solubility of pharmaceutical ingredients in triglycerides
    Brinkmann, J. and Huxoll, F. and Luebbert, C. and Sadowski, G.
    European Journal of Pharmaceutics and Biopharmaceutics 145 113-120 (2019)
    Lipid-based drug delivery systems (LBDDS) are highly relevant as pharmaceutical formulations significantly enhancing the bioavailability of active pharmaceutical ingredients (APIs). These formulations often are complex mixtures of APIs, various lipids, and other excipients (e.g. surfactants). In their simplest form, LBDDS contain one API being dissolved in a pure lipid, which often is a triglyceride (TG). In this work, solubilities of the APIs indomethacin, ibuprofen, and fenofibrate in pure TGs of different chain lengths (C chain 8–18) and degree of saturation were investigated. Solubilities of APIs in TGs were measured via differential scanning calorimetry, hot-stage microscopy, high-performance liquid chromatography, and Raman spectroscopy. The influence of fatty-acid chain length and degree of saturation on the API solubility in the TGs was investigated. APIs showed a higher solubility in saturated (wIBU = 10.5 wt% at 25 °C in tricaprylin) TGs compared to unsaturated ones (wIBU = 4.0 wt% at 25 °C in triolein). The fatty-acid chain length of TGs only slightly affects the solubility of ibuprofen and fenofibrate, but strongly influences the eutectic temperature of the API/TG mixtures. API solubilities in TGs and TG mixtures (mixtures of tricaprylin and tricaprin) were successfully modeled using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) accounting for the intermolecular API/TG interactions providing a deep understanding of the energetic and structural impact of the TGs on API solubility. © 2019 Elsevier B.V.
    view abstractdoi: 10.1016/j.ejpb.2019.10.012
  • 2019 • 512 Piezoelectric 3-D Fibrous Poly(3-hydroxybutyrate)-Based Scaffolds Ultrasound-Mineralized with Calcium Carbonate for Bone Tissue Engineering: Inorganic Phase Formation, Osteoblast Cell Adhesion, and Proliferation
    Chernozem, R.V. and Surmeneva, M.A. and Shkarina, S.N. and Loza, K. and Epple, M. and Ulbricht, M. and Cecilia, A. and Krause, B. and Baumbach, T. and Abalymov, A.A. and Parakhonskiy, B.V. and Skirtach, A.G. and Surmenev, R.A.
    ACS Applied Materials and Interfaces (2019)
    Elaboration of novel biocomposites providing simultaneously both biodegradability and stimulated bone tissue repair is essential for regenerative medicine. In particular, piezoelectric biocomposites are attractive because of a possibility to electrically stimulate cell response. In the present study, novel CaCO3-mineralized piezoelectric biodegradable scaffolds based on two polymers, poly[(R)3-hydroxybutyrate] (PHB) and poly[3-hydroxybutyrate-co-3-hydroxyvalerate] (PHBV), are presented. Mineralization of the scaffold surface is carried out by the in situ synthesis of CaCO3 in the vaterite and calcite polymorphs using ultrasound (U/S). Comparative characterization of PHB and PHBV scaffolds demonstrated an impact of the porosity and surface charge on the mineralization in a dynamic mechanical system, as no essential distinction was observed in wettability, structure, and surface chemical compositions. A significantly higher (4.3 times) piezoelectric charge and a higher porosity (∼15%) lead to a more homogenous CaCO3 growth in 3-D fibrous structures and result in a two times higher relative mass increase for PHB scaffolds compared to that for PHBV. This also increases the local ion concentration incurred upon mineralization under U/S-generated dynamic mechanical conditions. The modification of the wettability for PHB and PHBV scaffolds from hydrophobic (nonmineralized fibers) to superhydrophilic (mineralized fibers) led to a pronounced apatite-forming behavior of scaffolds in a simulated body fluid. In turn, this results in the formation of a dense monolayer of well-distributed and proliferated osteoblast cells along the fibers. CaCO3-mineralized PHBV surfaces had a higher osteoblast cell adhesion and proliferation assigned to a higher amount of CaCO3 on the surface compared to that on PHB scaffolds, as incurred from micro-computed tomography (μCT). Importantly, a cell viability study confirmed biocompatibility of all the scaffolds. Thus, hybrid biocomposites based on the piezoelectric PHB polymers represent an effective scaffold platform functionalized by an inorganic phase and stimulating the growth of the bone tissue. © 2019 American Chemical Society.
    view abstractdoi: 10.1021/acsami.9b04936
  • 2019 • 511 Development of filaments for fused deposition modeling 3D printing with medical grade poly(lactic-co-glycolic acid) copolymers
    Feuerbach, T. and Callau-Mendoza, S. and Thommes, M.
    Pharmaceutical Development and Technology 24 487-493 (2019)
    The manufacturing of custom implants and patient-tailored drug dosage forms with fused deposition modeling (FDM) three-dimensional (3D) printing is currently considered to be very promising. Most FDM printers are designed as an open filament system, for which filaments with a defined size are required. In addition to this processing requirement, the filament material must be of medical or pharmaceutical quality, in order to be suitable in these applications. In this work, filaments with nominal diameters of 1.75 mm and diameter tolerances of ±0.05 mm or lower were developed in a continuous extrusion process. The filaments were made from different medical grade poly(lactic-co-glycolic acid) (PLGA) copolymers. Thermal characterization of the material with differential scanning calorimetry (DSC) showed increased material degradation with increasing hydrophilicity. Mechanical characterization of the filaments showed tensile strengths in the range of 41–48 MPa and Young’s moduli in the range of 2055–2099 MPa. Stress relaxation tests showed no irreversible change in filament diameter under processing conditions similar to the utilized 3D printer. Due to unexpected differences in processability in the 3D printer, the molecular weight of the materials was identified as an additional relevant parameter. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
    view abstractdoi: 10.1080/10837450.2018.1514522
  • 2019 • 510 A new class of supramolecular ligands stabilizes 14-3-3 protein-protein interactions by up to two orders of magnitude
    Gigante, A. and Grad, J.-N. and Briels, J. and Bartel, M. and Hoffmann, D. and Ottmann, C. and Schmuck, C.
    Chemical Communications 55 111-114 (2019)
    We report the first supramolecular stabilizers of the interaction between 14-3-3ζ and two of its effectors, Tau and C-Raf, which are involved in neurodegenerative diseases and proliferative signal transduction, respectively. These supramolecular ligands open up an opportunity to modulate functions of 14-3-3 with these effectors. © The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c8cc07946c
  • 2019 • 509 Biomechanical stability and osteogenesis in a tibial bone defect treated by autologous ovine cord blood cells—a pilot study
    Herten, M. and Zilkens, C. and Thorey, F. and Tassemeier, T. and Lensing-Höhn, S. and Fischer, J.C. and Sager, M. and Krauspe, R. and Jäger, M.
    Molecules 24 (2019)
    The aim of this study was to elucidate the impact of autologous umbilical cord blood cells (USSC) on bone regeneration and biomechanical stability in an ovine tibial bone defect. Ovine USSC were harvested and characterized. After 12 months, full-size 2.0 cm mid-diaphyseal bone defects were created and stabilized by an external fixateur containing a rigidity measuring device. Defects were filled with (i) autologous USSC on hydroxyapatite (HA) scaffold (test group), (ii) HA scaffold without cells (HA group), or (iii) left empty (control group). Biomechanical measures, standardized X-rays, and systemic response controls were performed regularly. After six months, bone regeneration was evaluated histomorphometrically and labeled USSC were tracked. In all groups, the torsion distance decreased over time, and radiographies showed comparable bone regeneration. The area of newly formed bone was 82.5 ± 5.5% in the control compared to 59.2 ± 13.0% in the test and 48.6 ± 2.9% in the HA group. Labeled cells could be detected in lymph nodes, liver and pancreas without any signs of tumor formation. Although biomechanical stability was reached earliest in the test group with autologous USSC on HA scaffold, the density of newly formed bone was superior in the control group without any bovine HA. © 2019 by the authors.
    view abstractdoi: 10.3390/molecules24020295
  • 2019 • 508 Intrasurgical Protein Layer on Titanium Arthroplasty Explants: From the Big Twelve to the Implant Proteome
    Jäger, M. and Jennissen, H.P. and Haversath, M. and Busch, A. and Grupp, T. and Sowislok, A. and Herten, M.
    Proteomics - Clinical Applications 13 (2019)
    Purpose: Aseptic loosening in total joint replacement due to insufficient osteointegration is an unsolved problem in orthopaedics. The purpose of the study is to obtain a picture of the initial protein adsorption layer on femoral endoprosthetic surfaces as the key to the initiation of osseointegration. Experimental design: The paper describes the first study of femoral stem explants from patients for proteome analysis of the primary protein layer. After 2 min in situ, the stems are explanted and frozen in liquid nitrogen. Proteins are eluted under reducing conditions and analyzed by LC-MS/MS. Results: After exclusion of proteins identified by a single peptide, the implant proteome is found to consist of 2802 unique proteins. Of these, 77% are of intracellular origin, 9% are derived from the plasma proteome, 8% from the bone proteome, and four proteins with highest specificity score could be assigned to the bone marrow proteome (transcriptome). The most abundant protein in the adsorbed total protein layer is hemoglobin (8–11%) followed by serum albumin (3.6–6%). Conclusions: A detailed knowledge of the initial protein film deposited onto the implants, as demonstrated here for the first time, may help to understand and predict the response of the osseous microenvironment to implant surfaces. © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
    view abstractdoi: 10.1002/prca.201800168
  • 2019 • 507 Sites of high local frustration in DNA origami
    Kosinski, R. and Mukhortava, A. and Pfeifer, W. and Candelli, A. and Rauch, P. and Saccà, B.
    Nature Communications 10 (2019)
    The self-assembly of a DNA origami structure, although mostly feasible, represents indeed a rather complex folding problem. Entropy-driven folding and nucleation seeds formation may provide possible solutions; however, until now, a unified view of the energetic factors in play is missing. Here, by analyzing the self-assembly of origami domains with identical structure but different nucleobase composition, in function of variable design and experimental parameters, we identify the role played by sequence-dependent forces at the edges of the structure, where topological constraint is higher. Our data show that the degree of mechanical stress experienced by these regions during initial folding reshapes the energy landscape profile, defining the ratio between two possible global conformations. We thus propose a dynamic model of DNA origami assembly that relies on the capability of the system to escape high structural frustration at nucleation sites, eventually resulting in the emergence of a more favorable but previously hidden state. © 2019, The Author(s).
    view abstractdoi: 10.1038/s41467-019-09002-6
  • 2019 • 506 Dissociation of the Signaling Protein K-Ras4B from Lipid Membranes Induced by a Molecular Tweezer
    Li, L. and Erwin, N. and Möbitz, S. and Niemeyer, F. and Schrader, T. and Winter, R.H.A.
    Chemistry - A European Journal 25 9827-9833 (2019)
    Oncogenic Ras mutations occur in more than 30 % of human cancers. K-Ras4B is the most frequently mutated isoform of Ras proteins. Development of effective K-Ras4B inhibitors has been challenging, hence new approaches to inhibit this oncogenic protein are urgently required. The polybasic domain of K-Ras4B with its stretch of lysine residues is essential for its plasma membrane targeting and localization. Employing CD and fluorescence spectroscopy, confocal fluorescence, and atomic force microscopy we show that the molecular tweezer CLR01 is able to efficiently bind to the lysine stretch in the polybasic domain of K-Ras4B, resulting in dissociation of the K-Ras4B protein from the lipid membrane and disintegration of K-Ras4B nanoclusters in the lipid bilayer. These results suggest that targeting of the polybasic domain of K-Ras4B by properly designed tweezers might represent an effective strategy for inactivation of K-Ras4B signaling. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
    view abstractdoi: 10.1002/chem.201901861
  • 2019 • 505 The molecular tweezer CLR01 inhibits aberrant superoxide dismutase 1 (SOD1) self-assembly in vitro and in the G93A-SOD1 mouse model of ALS
    Malik, R. and Meng, H. and Wongkongkathep, P. and Corrales, C.I. and Sepanj, N. and Atlasi, R.S. and Klärner, F.-G. and Schrader, T. and Spencer, M.J. and Loo, J.A. and Wiedau, M. and Bitan, G.
    Journal of Biological Chemistry 294 3501-3513 (2019)
    Mutations in superoxide dismutase 1 (SOD1) cause 15–20% of familial amyotrophic lateral sclerosis (fALS) cases. The resulting amino acid substitutions destabilize SOD1’s protein structure, leading to its self-assembly into neurotoxic oligomers and aggregates, a process hypothesized to cause the characteristic motor-neuron degeneration in affected individuals. Currently, effective disease-modifying therapy is not available for ALS. Molecular tweezers prevent formation of toxic protein assemblies, yet their protective action has not been tested previously on SOD1 or in the context of ALS. Here, we tested the molecular tweezer CLR01–a broad-spectrum inhibitor of the self-assembly and toxicity of amyloid proteins–as a potential therapeutic agent for ALS. Using recombinant WT and mutant SOD1, we found that CLR01 inhibited the aggregation of all tested SOD1 forms in vitro. Next, we examined whether CLR01 could prevent the formation of misfolded SOD1 in the G93A-SOD1 mouse model of ALS and whether such inhibition would have a beneficial therapeutic effect. CLR01 treatment decreased misfolded SOD1 in the spinal cord significantly. However, these histological findings did not correlate with improvement of the disease phenotype. A small, dose-dependent decrease in disease duration was found in CLR01-treated mice, relative to vehicle-treated animals, yet motor function did not improve in any of the treatment groups. These results demonstrate that CLR01 can inhibit SOD1 misfolding and aggregation both in vitro and in vivo, but raise the question whether such inhibition is sufficient for achieving a therapeutic effect. Additional studies in other less aggressive ALS models may be needed to determine the therapeutic potential of this approach. © 2019 Malik et al.
    view abstractdoi: 10.1074/jbc.RA118.005940
  • 2019 • 504 Native Top-Down Mass Spectrometry and Ion Mobility Spectrometry of the Interaction of Tau Protein with a Molecular Tweezer Assembly Modulator
    Nshanian, M. and Lantz, C. and Wongkongkathep, P. and Schrader, T. and Klärner, F.-G. and Blümke, A. and Despres, C. and Ehrmann, M. and Smet-Nocca, C. and Bitan, G. and Loo, J.A.
    Journal of the American Society for Mass Spectrometry 30 16-23 (2019)
    Native top-down mass spectrometry (MS) and ion mobility spectrometry (IMS) were applied to characterize the interaction of a molecular tweezer assembly modulator, CLR01, with tau, a protein believed to be involved in a number of neurodegenerative disorders, including Alzheimer’s disease. The tweezer CLR01 has been shown to inhibit aggregation of amyloidogenic polypeptides without toxic side effects. ESI-MS spectra for different forms of tau protein (full-length, fragments, phosphorylated, etc.) in the presence of CLR01 indicate a primary binding stoichiometry of 1:1. The relatively high charging of the protein measured from non-denaturing solutions is typical of intrinsically disordered proteins, such as tau. Top-down mass spectrometry using electron capture dissociation (ECD) is a tool used to determine not only the sites of post-translational modifications but also the binding site(s) of non-covalent interacting ligands to biomolecules. The intact protein and the protein-modulator complex were subjected to ECD-MS to obtain sequence information, map phosphorylation sites, and pinpoint the sites of inhibitor binding. The ESI-MS study of intact tau proteins indicates that top-down MS is amenable to the study of various tau isoforms and their post-translational modifications (PTMs). The ECD-MS data point to a CLR01 binding site in the microtubule-binding region of tau, spanning residues K294-K331, which includes a six-residue nucleating segment PHF6 (VQIVYK) implicated in aggregation. Furthermore, ion mobility experiments on the tau fragment in the presence of CLR01 and phosphorylated tau reveal a shift towards a more compact structure. The mass spectrometry study suggests a picture for the molecular mechanism of the modulation of protein-protein interactions in tau by CLR01. [Figure not available: see fulltext.]. © 2018, American Society for Mass Spectrometry.
    view abstractdoi: 10.1007/s13361-018-2027-6
  • 2019 • 503 2-Azo-, 2-diazocine-thiazols and 2-azo-imidazoles as photoswitchable kinase inhibitors: Limitations and pitfalls of the photoswitchable inhibitor approach
    Schehr, M. and Ianes, C. and Weisner, J. and Heintze, L. and Müller, M.P. and Pichlo, C. and Charl, J. and Brunstein, E. and Ewert, J. and Lehr, M. and Baumann, U. and Rauh, D. and Knippschild, U. and Peifer, C. and Herges, R.
    Photochemical and Photobiological Sciences 18 1398-1407 (2019)
    In photopharmacology, photoswitchable compounds including azobenzene or other diarylazo moieties exhibit bioactivity against a target protein typically in the slender E-configuration, whereas the rather bulky Z-configuration usually is pharmacologically less potent. Herein we report the design, synthesis and photochemical/inhibitory characterization of new photoswitchable kinase inhibitors targeting p38α MAPK and CK1δ. A well characterized inhibitor scaffold was used to attach arylazo- and diazocine moieties. When the isolated isomers, or the photostationary state (PSS) of isomers, were tested in commonly used in vitro kinase assays, however, only small differences in activity were observed. X-ray analyses of ligand-bound p38α MAPK and CK1δ complexes revealed dynamic conformational adaptations of the protein with respect to both isomers. More importantly, irreversible reduction of the azo group to the corresponding hydrazine was observed. Independent experiments revealed that reducing agents such as DTT (dithiothreitol) and GSH (glutathione) that are typically used for protein stabilization in biological assays were responsible. Two further sources of error are the concentration dependence of the E-Z-switching efficiency and artefacts due to incomplete exclusion of light during testing. Our findings may also apply to a number of previously investigated azobenzene-based photoswitchable inhibitors. © 2019 The Royal Society of Chemistry and Owner Societies.
    view abstractdoi: 10.1039/c9pp00010k
  • 2019 • 502 ImmunoSERS microscopy for the detection of smooth muscle cells in atherosclerotic plaques
    Wiercigroch, E. and Stepula, E. and Mateuszuk, L. and Zhang, Y. and Baranska, M. and Chlopicki, S. and Schlücker, S. and Malek, K.
    Biosensors and Bioelectronics 133 79-85 (2019)
    We investigated the suitability of immuno-SERS (iSERS) microscopy for imaging of smooth muscle cells (SMCs) in atherosclerotic plaques. Localization of SMCs is achieved by using SERS-labelled antibodies direct against alpha-smooth muscle actin (SMA). The staining quality of the false-colour iSERS images obtained by confocal Raman microscopy with point mapping is compared with wide-field immunofluorescence images. Both direct (labelled primary antibody) and indirect iSERS staining (unlabelled primary and labelled secondary antibody) techniques were employed. Direct iSERS staining yields results comparable to indirect IF staining, demonstrating the suitability of iSERS in research on atherosclerosis and paving the way for future multiplexed imaging experiments. © 2019 Elsevier B.V.
    view abstractdoi: 10.1016/j.bios.2019.02.068
  • 2019 • 501 Sensitive and selective detection of Cu2+ ions based on fluorescent Ag nanoparticles synthesized by R-phycoerythrin from marine algae Porphyra yezoensis
    Xu, Y. and Hou, Y. and Wang, Y. and Wang, Y. and Li, T. and Song, C. and Wei, N. and Wang, Q.
    Ecotoxicology and Environmental Safety 168 356-362 (2019)
    In this study, using a natural and green protein R-phycoerythrin (R-PE) extracted from marine Porphyra yezoensis as the stabilizer and reducer, silver nanoparticles (AgNPs) were synthesized. Based on this, a highly sensitive and selective method for the detection of Cu2+ ions was developed using R-PE-AgNPs as fluorescent probe. The interactions between R-PE-AgNPs and Cu2+ ions were systematically characterized by fluorescence spectroscopy, transmission electron microscopy (TEM), elemental mapping and Fourier transform infrared (FTIR). It was found that Cu2+ ions could cause aggregation of the R-PE-AgNPs, accompanied by the greatly increased particle size. Importantly, the method offered a wide linear detection range from 0 μM to 100.0 μM with a detection limit of 0.0190 μM. Moreover, the proposed method was successfully applied to analyze Cu2+ ions in tap water and lake water samples, acquiring satisfactory recovery between 91.6% and 102.2%. Such a green, fast and cost-effective fluorimetric method of the R-PE-AgNPs probe has great potential for tracing Cu2+ ions in diverse aqueous media. © 2018 Elsevier Inc.
    view abstractdoi: 10.1016/j.ecoenv.2018.10.102
  • 2019 • 500 Extended Operational Lifetime of a Photosystem-Based Bioelectrode
    Zhao, F. and Ruff, A. and Rögner, M. and Schuhmann, W. and Conzuelo, F.
    Journal of the American Chemical Society 141 5102-5106 (2019)
    The development of bioelectrochemical assemblies for sustainable energy transformation constitutes an increasingly important field of research. Significant progress has been made in the development of semiartificial devices for conversion of light into electrical energy by integration of photosynthetic biomolecules on electrodes. However, sufficient long-term stability of such biophotoelectrodes has been compromised by reactive species generated under aerobic operation. Therefore, meeting the requirements of practical applications still remains unsolved. We present the operation of a photosystem I-based photocathode using an electron acceptor that enables photocurrent generation under anaerobic conditions as the basis for a biodevice with substantially improved stability. A continuous operation lifetime considerably superior to previous reports and at higher light intensities is paving the way toward the potential application of semiartificial energy conversion devices. © 2019 American Chemical Society.
    view abstractdoi: 10.1021/jacs.8b13869
  • 2018 • 499 Human Apolipoprotein A1 at Solid/Liquid and Liquid/Gas Interfaces
    Dogan, S. and Paulus, M. and Forov, Y. and Weis, C. and Kampmann, M. and Cewe, C. and Kiesel, I. and Degen, P. and Salmen, P. and Rehage, H. and Tolan, M.
    Journal of Physical Chemistry B 122 3953-3960 (2018)
    An X-ray reflectivity study on the adsorption behavior of human apolipoprotein A1 (apoA1) at hydrophilic and hydrophobic interfaces is presented. It is shown that the protein interacts via electrostatic and hydrophobic interactions with the interfaces, resulting in the absorption of the protein. pH dependent measurements at the solid/liquid interface between silicon dioxide and aqueous protein solution show that in a small pH range between pH 4 and 6, adsorption is increased due to electrostatic attraction. Here, the native shape of the protein seems to be conserved. In contrast, the adsorption at the liquid/gas interface is mainly driven by hydrophobic effects, presumably by extending the hydrophobic regions of the amphipathic helices, and results in a conformational change of the protein during adsorption. However, the addition of differently charged membrane-forming lipids at the liquid/gas interface illustrates the ability of apoA1 to include lipids, resulting in a depletion of the lipids from the interface. © 2018 American Chemical Society.
    view abstractdoi: 10.1021/acs.jpcb.7b12481
  • 2018 • 498 Norbornane-based cationic antimicrobial peptidomimetics targeting the bacterial membrane
    Hickey, S.M. and Ashton, T.D. and Boer, G. and Bader, C.A. and Thomas, M. and Elliott, A.G. and Schmuck, C. and Yu, H.Y. and Li, J. and Nation, R.L. and Cooper, M.A. and Plush, S.E. and Brooks, D.A. and Pfeffer, F.M.
    European Journal of Medicinal Chemistry 160 9-22 (2018)
    The design, synthesis and evaluation of a small series of potent amphiphilic norbornane antibacterial agents has been performed (compound 10 MIC = 0.25 μg/mL against MRSA). Molecular modelling indicates rapid aggregation of this class of antibacterial agent prior to membrane association and insertion. Two fluorescent analogues (compound 29 with 4-amino-naphthalimide and 34 with 4-nitrobenz-2-oxa-1,3-diazole fluorophores) with good activity (MIC = 0.5 μg/mL against MRSA) were also constructed and confocal microscopy studies indicate that the primary site of interaction for this family of compounds is the bacterial membrane. © 2018 Elsevier Masson SAS
    view abstractdoi: 10.1016/j.ejmech.2018.09.072
  • 2018 • 497 Spectroscopical investigations on the redox chemistry of [FeFe]-hydrogenases in the presence of carbon monoxide
    Laun, K. and Mebs, S. and Duan, J. and Wittkamp, F. and Apfel, U.-P. and Happe, T. and Winkler, M. and Haumann, M. and Stripp, S.T.
    Molecules 23 1-13 (2018)
    [FeFe]-hydrogenases efficiently catalyzes hydrogen conversion at a unique [4Fe–4S]-[FeFe] cofactor, the so-called H-cluster. The catalytic reaction occurs at the diiron site, while the [4Fe–4S] cluster functions as a redox shuttle. In the oxidized resting state (Hox), the iron ions of the diiron site bind one cyanide (CN−) and carbon monoxide (CO) ligand each and a third carbonyl can be found in the Fe–Fe bridging position (µCO). In the presence of exogenous CO, A fourth CO ligand binds at the diiron site to form the oxidized, CO-inhibited H-cluster (Hox-CO). We investigated the reduced, CO-inhibited H-cluster (Hred´-CO) in this work. The stretching vibrations of the diatomic ligands were monitored by attenuated total reflection Fourier-transform infrared spectroscopy (ATR FTIR). Density functional theory (DFT) at the TPSSh/TZVP level was employed to analyze the cofactor geometry, as well as the redox and protonation state of the H-cluster. Selective 13CO isotope editing, spectro-electrochemistry, and correlation analysis of IR data identified a one-electron reduced, protonated [4Fe–4S] cluster and an apical CN− ligand at the diiron site in Hred´-CO. The reduced, CO-inhibited H-cluster forms independently of the sequence of CO binding and cofactor reduction, which implies that the ligand rearrangement at the diiron site upon CO inhibition is independent of the redox and protonation state of the [4Fe–4S] cluster. The relation of coordination dynamics to cofactor redox and protonation changes in hydrogen conversion catalysis and inhibition is discussed. © 2018 by the authors.
    view abstractdoi: 10.3390/molecules23071669
  • 2018 • 496 Optimization of pellets manufacturing process using rough set theory
    Pałkowski, Ł. and Karolak, M. and Kubiak, B. and Błaszczyński, J. and Słowiński, R. and Thommes, M. and Kleinebudde, P. and Krysiński, J.
    European Journal of Pharmaceutical Sciences 124 295-303 (2018)
    Pharmaceutical pellets are spherical agglomerates manufactured in extrusion/spheronization process. The composition of the pellets, the amount of active pharmaceutical ingredient (API) and the type of used excipients have an influence on the shape and quality of dosage form. A proper quality of the pellets can also be achieved by identifying the most important technological process parameters. In this paper, a knowledge discovery method, called dominance-based rough set approach (DRSA) has been applied to evaluate critical process parameters in pellets manufacturing. For this purpose, a set of condition attributes (amount of API; type and amount of excipient used; process parameters such as screw and rotation speed, time and temperature of spheronization) and a decision attribute (quality of the pellets defined by the aspect ratio) were used to set up an information system. The DRSA analysis allowed to induce decision rules containing information about process parameters which have a significant impact on the quality of manufactured pellets. Those rules can be used to optimize the process of pellets manufacturing. © 2018 Elsevier B.V.
    view abstractdoi: 10.1016/j.ejps.2018.08.027
  • 2018 • 495 Direct monitoring of the conformational equilibria of the activation loop in the mitogen-activated protein kinase p38α
    Roser, P. and Weisner, J. and Simard, J.R. and Rauh, D. and Drescher, M.
    Chemical Communications 54 12057-12060 (2018)
    Conformational transitions in protein kinases are crucial for the biological function of these enzymes. Here, we characterize and assess conformational equilibria of the activation loop and the effect of small molecule inhibitors in the MAP kinase p38α. Our work experimentally revealed the existence of a two-state equilibrium for p38α while the addition of inhibitors shifts the equilibrium between these two states. © 2018 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c8cc06128a
  • 2018 • 494 A fully protected hydrogenase/polymer-based bioanode for high-performance hydrogen/glucose biofuel cells
    Ruff, A. and Szczesny, J. and Marković, N. and Conzuelo, F. and Zacarias, S. and Pereira, I.A.C. and Lubitz, W. and Schuhmann, W.
    Nature Communications 9 (2018)
    Hydrogenases with Ni- and/or Fe-based active sites are highly active hydrogen oxidation catalysts with activities similar to those of noble metal catalysts. However, the activity is connected to a sensitivity towards high-potential deactivation and oxygen damage. Here we report a fully protected polymer multilayer/hydrogenase-based bioanode in which the sensitive hydrogen oxidation catalyst is protected from high-potential deactivation and from oxygen damage by using a polymer multilayer architecture. The active catalyst is embedded in a low-potential polymer (protection from high-potential deactivation) and covered with a polymer-supported bienzymatic oxygen removal system. In contrast to previously reported polymer-based protection systems, the proposed strategy fully decouples the hydrogenase reaction form the protection process. Incorporation of the bioanode into a hydrogen/glucose biofuel cell provides a benchmark open circuit voltage of 1.15 V and power densities of up to 530 µW cm−2 at 0.85 V. © 2018, The Author(s).
    view abstractdoi: 10.1038/s41467-018-06106-3
  • 2018 • 493 Sorption mechanisms of chlorinated hydrocarbons on biochar produced from different feedstocks: Conclusions from single- and bi-solute experiments
    Schreiter, I.J. and Schmidt, W. and Schüth, C.
    Chemosphere 203 34-43 (2018)
    Biochar is increasingly deemed a potential sorbent for contaminants in soil and water remediation. We tested three biochars from different feedstocks (cattle manure, grain husk, and wood chips) produced at relatively low pyrolysis temperature (450 °C), for their sorption behavior towards trichloroethylene (TCE) and tetrachloroethylene (PCE) in single- and bi-solute systems. In single-solute experiments, all biochars show stronger sorption for TCE (about 50% based on solubility-normalized Freundlich coefficients). The lower sorption of PCE is attributed to steric effects, e.g. size exclusion in small micropores and specific interactions. Plant-derived, carbon-rich biochars with high specific surface area and microporosity predominantly sorb via pore-filling, as also observed in activated carbon. Biochar produced from manure, with higher ash content and polarity, and smaller total pore volume (PVtot), shows significant contribution of partitioning. These findings also apply to bi-solute systems. TCE and PCE show different competition behavior depending on biochar properties. Plant-based biochars are pore-filling-dominated and show strong competition. However, competition behavior in microporous biochars depends on the concentration range. Manure biochar with high polarity and low PVtot shows significant partitioning and therefore less competition. Compared to the plant-based chars competition in manure biochar is not concentration-dependent. These results indicate that biochars with a large fraction of non-carbonized phase facilitate non-competitive sorption and might be a valuable sorbent in mixed contaminant systems. © 2018 Elsevier Ltd
    view abstractdoi: 10.1016/j.chemosphere.2018.03.173
  • 2018 • 492 Co-solvent effects on reaction rate and reaction equilibrium of an enzymatic peptide hydrolysis
    Wangler, A. and Canales, R. and Held, C. and Luong, T.Q. and Winter, R. and Zaitsau, D.H. and Verevkin, S.P. and Sadowski, G.
    Physical Chemistry Chemical Physics 20 11317-11326 (2018)
    This work presents an approach that expresses the Michaelis constant KaM and the equilibrium constant Kth of an enzymatic peptide hydrolysis based on thermodynamic activities instead of concentrations. This provides KaM and Kth values that are independent of any co-solvent. To this end, the hydrolysis reaction of N-succinyl-l-phenylalanine-p-nitroanilide catalysed by the enzyme α-chymotrypsin was studied in pure buffer and in the presence of the co-solvents dimethyl sulfoxide, trimethylamine-N-oxide, urea, and two salts. A strong influence of the co-solvents on the measured Michaelis constant (KM) and equilibrium constant (Kx) was observed, which was found to be caused by molecular interactions expressed as activity coefficients. Substrate and product activity coefficients were used to calculate the activity-based values KaM and Kth for the co-solvent free reaction. Based on these constants, the co-solvent effect on KM and Kx was predicted in almost quantitative agreement with the experimental data. The approach presented here does not only reveal the importance of understanding the thermodynamic non-ideality of reactions taking place in biological solutions and in many technological applications, it also provides a framework for interpreting and quantifying the multifaceted co-solvent effects on enzyme-catalysed reactions that are known and have been observed experimentally for a long time. © the Owner Societies.
    view abstractdoi: 10.1039/c7cp07346a
  • 2018 • 491 Hydrogenases: Recent developments and future perspectives
    Wittkamp, F. and Senger, M. and Stripp, S.T. and Apfel, U.-P.
    Chemical Communications 54 5934-5942 (2018)
    [FeFe]-Hydrogenases are the most efficient enzymes for catalytic hydrogen turnover. Their H2 production efficiency is hitherto unrivalled. However, functional details of the catalytic machinery and possible modes of application are discussed controversially. The incorporation of synthetically modified cofactors and utilization of semi-artificial enzymes only recently allowed us to shed light on key steps of the catalytic cycle. Herein, we summarize the essential findings regarding the redox chemistry of [FeFe]-hydrogenases and discuss their catalytic hydrogen turnover. We furthermore will give an outlook on potential research activities and exploit the utilization of synthetic cofactor mimics. © 2018 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c8cc01275j
  • 2018 • 490 Molecular recognition of carboxylates in the protein leucine zipper by a multivalent supramolecular ligand: Residue-specific, sensitive and label-free probing by UV resonance Raman spectroscopy
    Zakeri, B. and Niebling, S. and Martinéz, A.G. and Sokkar, P. and Sanchez-Garcia, E. and Schmuck, C. and Schlücker, S.
    Physical Chemistry Chemical Physics 20 1817-1820 (2018)
    Ultraviolet resonance Raman (UVRR) spectroscopy is a selective, sensitive and label-free vibrational spectroscopic technique. Here, we demonstrate as proof of concept that UVRR can be used for probing the recognition between a multivalent supramolecular ligand and acidic residues in leucine zipper, an α-helical structural motif of many proteins. © 2017 Owner Societies.
    view abstractdoi: 10.1039/c7cp04971d
  • 2018 • 489 On-surface nickel porphyrin mimics the reactive center of an enzyme cofactor
    Zamborlini, G. and Jugovac, M. and Cossaro, A. and Verdini, A. and Floreano, L. and Lüftner, D. and Puschnig, P. and Feyer, V. and Schneider, C.M.
    Chemical Communications 54 13423-13426 (2018)
    Metal-containing enzyme cofactors achieve their unusual reactivity by stabilizing uncommon metal oxidation states with structurally complex ligands. In particular, the specific cofactor promoting both methanogenesis and anaerobic methane oxidation is a porphyrinoid chelated to a nickel(i) atom via a multi-step biosynthetic path, where nickel reduction is achieved through extensive molecular hydrogenation. Here, we demonstrate an alternative route to porphyrin reduction by charge transfer from a selected copper substrate to commercially available 5,10,15,20-tetraphenyl-porphyrin nickel(ii). X-ray absorption measurements at the Ni L3-edge unequivocally show that NiTPP species adsorbed on Cu(100) are stabilized in the highly reactive Ni(i) oxidation state by electron transfer to the molecular orbitals. Our approach highlights how some fundamental properties of synthetically inaccessible biological cofactors may be reproduced by hybridization of simple metalloporphyrins with metal surfaces, with implications towards novel approaches to heterogenous catalysis. © 2018 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c8cc06739b
  • 2017 • 488 Polybenzoxazine-Derived N-doped Carbon as Matrix for Powder-Based Electrocatalysts
    Barwe, S. and Andronescu, C. and Masa, J. and Ventosa, E. and Klink, S. and Genç, A. and Arbiol, J. and Schuhmann, W.
    ChemSusChem 10 2653-2659 (2017)
    In addition to catalytic activity, intrinsic stability, tight immobilization on a suitable electrode surface, and sufficient electronic conductivity are fundamental prerequisites for the long-term operation of particle- and especially powder-based electrocatalysts. We present a novel approach to concurrently address these challenges by using the unique properties of polybenzoxazine (pBO) polymers, namely near-zero shrinkage and high residual-char yield even after pyrolysis at high temperatures. Pyrolysis of a nanocubic prussian blue analogue precursor (KmMnx[Co(CN)6]y⋅n H2O) embedded in a bisphenol A and aniline-based pBO led to the formation of a N-doped carbon matrix modified with MnxCoyOz nanocubes. The obtained electrocatalyst exhibits high efficiency toward the oxygen evolution reaction (OER) and more importantly a stable performance for at least 65 h. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
    view abstractdoi: 10.1002/cssc.201700593
  • 2017 • 487 Structure-based design, synthesis and crystallization of 2-arylquinazolines as lipid pocket ligands of p38α MAPK
    Bührmann, M. and Wiedemann, B.M. and Müller, M.P. and Hardick, J. and Ecke, M. and Rauh, D.
    PLoS ONE 12 (2017)
    In protein kinase research, identifying and addressing small molecule binding sites other than the highly conserved ATP-pocket are of intense interest because this line of investigation extends our understanding of kinase function beyond the catalytic phosphotransfer. Such alternative binding sites may be involved in altering the activation state through subtle conformational changes, control cellular enzyme localization, or in mediating and disrupting protein-protein interactions. Small organic molecules that target these less conserved regions might serve as tools for chemical biology research and to probe alternative strategies in targeting protein kinases in disease settings. Here, we present the structure-based design and synthesis of a focused library of 2-arylquinazoline derivatives to target the lipophilic C-terminal binding pocket in p38α MAPK, for which a clear biological function has yet to be identified. The interactions of the ligands with p38α MAPK was analyzed by SPR measurements and validated by protein X-ray crystallography. © 2017 Bührmann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
    view abstractdoi: 10.1371/journal.pone.0184627
  • 2017 • 486 Structure-Guided Development of Covalent and Mutant-Selective Pyrazolopyrimidines to Target T790M Drug Resistance in Epidermal Growth Factor Receptor
    Engel, J. and Smith, S. and Lategahn, J. and Tumbrink, H.L. and Goebel, L. and Becker, C. and Hennes, E. and Keul, M. and Unger, A. and Müller, H. and Baumann, M. and Schultz-Fademrecht, C. and Günther, G. and Hengstler, J.G. and Rauh, D.
    Journal of Medicinal Chemistry 60 7725-7744 (2017)
    Reversible epidermal growth factor receptor (EGFR) inhibitors prompt a beneficial clinical response in non-small cell lung cancer patients who harbor activating mutations in EGFR. However, resistance mutations, particularly the gatekeeper mutation T790M, limit this efficacy. Here, we describe a structure-guided development of a series of covalent and mutant-selective EGFR inhibitors that effectively target the T790M mutant. The pyrazolopyrimidine-based core differs structurally from that of aminopyrimidine-based third-generation EGFR inhibitors and therefore constitutes a new set of inhibitors that target this mechanism of drug resistance. These inhibitors exhibited strong inhibitory effects toward EGFR kinase activity and excellent inhibition of cell growth in the drug-resistant cell line H1975, without significantly affecting EGFR wild-type cell lines. Additionally, we present the in vitro ADME/DMPK parameters for a subset of the inhibitors as well as in vivo pharmacokinetics in mice for a candidate with promising activity profile. © 2017 American Chemical Society.
    view abstractdoi: 10.1021/acs.jmedchem.7b00515
  • 2017 • 485 The proteome of baker's yeast mitochondria
    Gonczarowska-Jorge, H. and Zahedi, R.P. and Sickmann, A.
    Mitochondrion 33 15-21 (2017)
    In the past decade mass spectrometry-based proteomics has greatly contributed to shaping our knowledge about . Saccharomyces cerevisiae mitochondria, from the initial identification of novel essential components in purified protein complexes, to the actual characterization of the mitochondrial proteome, the specific analysis of mitochondrial subcompartment proteomes, and the study of regulatory mechanisms that govern mitochondrial homeostasis. Here, we provide an overview of relevant mitochondrial proteome studies and furthermore discuss future possibilities how proteomics will further improve our existing understanding of mitochondria. Although mitochondria were the first organelles that have been intensively studied using proteomics, indeed the recent progress and development of more powerful and sensitive methods, instrumentation and data analysis strategies indicate that we are only beginning to exploit the full potential of mitochondrial proteomics and its possibilities to decipher cell biology. Beside mere (quantitative) inventory under different conditions, this will for instance include studying the role of multiple post-translational modifications in mitochondrial homeostasis as well as the system-wide mapping of protein-protein complexes and protein-lipid interactions. © 2016.
    view abstractdoi: 10.1016/j.mito.2016.08.007
  • 2017 • 484 Optimized expression-based microdissection of formalin-fixed lung cancer tissue
    Grafen, M. and Hofmann, T.R. and Scheel, A.H. and Beck, J. and Emmert, A. and Küffer, S. and Danner, B.C. and Schütz, E. and Büttner, R. and Ostendorf, A. and Ströbel, P. and Bohnenberger, H.
    Laboratory Investigation 97 863-872 (2017)
    Analysis of specific DNA alterations in precision medicine of tumors is crucially important for molecular targeted treatments. Lung cancer is a prototypic example and one of the leading causes of cancer-related deaths worldwide. One major technical problem of detecting DNA alterations in tissue samples is cellular heterogeneity, that is, mixture of tumor and normal cells. Microdissection is an important tool to enrich tumor cells from heterogeneous tissue samples. However, conventional laser capture microdissection has several disadvantages like user-dependent selection of regions of interest (ROI), high costs for dissection systems and long processing times. ROI selection in expression-based microdissection (xMD) directly relies on cancer cell-specific immunostaining. Whole-slide irradiation leads to localized energy absorption at the sites of most intensive staining and melting of a membrane covering the slide, so that tumor cells can be isolated by removing the complete membrane. In this study, we optimized xMD of lung cancer tissue by enhancing staining intensity of tumor cell-specific immunostaining and processing of the stained samples. This optimized procedure did not alter DNA quality and resulted in enrichment of mutated EGFR DNA from lung adenocarcinoma specimens after xMD. We here also introduce a quality control protocol based on digital whole-slide scanning and image analysis before and after xMD to quantify selectivity and efficiency of the procedure. In summary, this study provides a workflow for xMD, adapted and tested for lung cancer tissue that can be used for lung tumor cell dissection before diagnostic or investigatory analyses. © 2017 USCAP, Inc All rights reserved.
    view abstractdoi: 10.1038/labinvest.2017.31
  • 2017 • 483 Trisubstituted Pyridinylimidazoles as Potent Inhibitors of the Clinically Resistant L858R/T790M/C797S EGFR Mutant: Targeting of Both Hydrophobic Regions and the Phosphate Binding Site
    Günther, M. and Lategahn, J. and Juchum, M. and Döring, E. and Keul, M. and Engel, J. and Tumbrink, H.L. and Rauh, D. and Laufer, S.
    Journal of Medicinal Chemistry 60 5613-5637 (2017)
    Inhibition of the epidermal growth factor receptor represents one of the most promising strategies in the treatment of lung cancer. Acquired resistance compromises the clinical efficacy of EGFR inhibitors during long-term treatment. The recently discovered EGFR-C797S mutation causes resistance against third-generation EGFR inhibitors. Here we present a rational approach based on extending the inhibition profile of a p38 MAP kinase inhibitor toward mutant EGFR inhibition. We used a privileged scaffold with proven cellular potency as well as in vivo efficacy and low toxicity. Guided by molecular modeling, we synthesized and studied the structure-activity relationship of 40 compounds against clinically relevant EGFR mutants. We successfully improved the cellular EGFR inhibition down to the low nanomolar range with covalently binding inhibitors against a gefitinib resistant T790M mutant cell line. We identified additional noncovalent interactions, which allowed us to develop metabolically stable inhibitors with high activities against the osimertinib resistant L858R/T790M/C797S mutant. © 2017 American Chemical Society.
    view abstractdoi: 10.1021/acs.jmedchem.7b00316
  • 2017 • 482 Optimized 4,5-diarylimidazoles as potent/selective inhibitors of Protein Kinase CK1δ and their structural relation to P38α MAPK
    Halekotte, J. and Witt, L. and Ianes, C. and Krüger, M. and Bührmann, M. and Rauh, D. and Pichlo, C. and Brunstein, E. and Luxenburger, A. and Baumann, U. and Knippschild, U. and Bischof, J. and Peifer, C. and Koch, P. and Laufer, S.
    Molecules 22 (2017)
    The involvement of protein kinase CK1δ in the pathogenesis of severe disorders such as Alzheimer's disease, amyotrophic lateral sclerosis, familial advanced sleep phase syndrome, and cancer has dramatically increased interest in the development of effective small molecule inhibitors for both therapeutic application and basic research. Unfortunately the design of CK1 isoform-specific compounds has proved to be highly complicated due to the existence of six evolutionarily conserved human CK1 members that possess similar, different, or even opposite physiological and pathophysiological implications. Consequently only few potent and selective CK1δ inhibitors have been reported so far and structurally divergent approaches are urgently needed in order to establish SAR that might enable complete discrimination of CK1 isoforms and related p38α MAPK. In this study we report on design and characterization of optimized 4,5-diarylimidazoles as highly effective ATP-competitive inhibitors of CK1δ with compounds 11b (IC50 CK1δ = 4 nM, IC50 CK1ϵ = 25 nM), 12a (IC50 CK1δ = 19 nM, IC50 CK1ϵ = 227 nM), and 16b (IC50 CK1δ = 8 nM, IC50 CK1ϵ = 81 nM) being among the most potent CK1δ-targeting agents published to date. Inhibitor compound 11b, displaying potential as a pharmacological tool, has further been profiled over a panel of 321 protein kinases exhibiting high selectivity. Cellular efficacy has been evaluated in human pancreatic cancer cell lines Colo357 (EC50 = 3.5 μM) and Panc89 (EC50 = 1.5 μM). SAR is substantiated by X-ray crystallographic analysis of 16b in CK1δ and 11b in p38α. © 2017 by the authors.
    view abstractdoi: 10.3390/molecules22040522
  • 2017 • 481 Compositional fingerprint of soy sauces via hydrophobic surface interaction
    Jakobi, V. and Salmen, P. and Paulus, M. and Tolan, M. and Rosenhahn, A.
    Food Chemistry 218 256-260 (2017)
    In this work, the interaction of soy sauces with hydrophobic surfaces has been analyzed. Hydrophobic self-assembled monolayers on gold or silicon dioxide were used to harvest conditioning layers from soy sauce products with varying amounts of additives. The data was compared to adsorption of soy protein and glutamic acid as common ingredients. Spectral ellipsometry revealed that all tested sauces led to the formation of thin overlayers on hydrophobic surfaces. Products with less additives yielded adlayers in the same thickness range as pure soy protein. In contrast, sauces with more ingredients create distinctly thicker films. Using water contact angle goniometry, it is shown that all adlayers render the substrate more hydrophilic. Infrared spectroscopy provided a deeper insight into the adlayer chemistry and revealed that the adlayer composition is dominated by protein rich components. X-ray reflectivity on selected films provided further insight into the density profiles within the adlayers on the molecular scale. © 2016 Elsevier Ltd
    view abstractdoi: 10.1016/j.foodchem.2016.09.045
  • 2017 • 480 A Systematic Structure–Activity Study of a New Type of Small Peptidic Transfection Vector Reveals the Importance of a Special Oxo-Anion-Binding Motif for Gene Delivery
    Junghänel, S. and Karczewski, S. and Bäcker, S. and Knauer, S.K. and Schmuck, C.
    ChemBioChem 18 2268-2279 (2017)
    We discovered a new class of artificial peptidic transfection vectors based on an artificial anion-binding motif, the guanidiniocarbonylpyrrole (GCP) cation. This new type of vector is surprisingly smaller than traditional systems, and our previous work suggested that the GCP group was important for promoting critical endosomal escape. We now present here a systematic comparison of similar DNA ligands featuring our GCP oxo-anion-binding motif with DNA ligands only consisting of naturally occurring amino acids. Structure–activity studies showed that the artificial binding motif clearly outperformed natural amino acids such as histidine, lysine, and arginine. It improved the ability to shuttle foreign genetic material into cells, yet successfully mediated endosomal escape. Also, plasmids that were complexed by our artificial ligands were stabilized against cytosolic degradation to some extent. This resulted in the successful expression of plasmid information (comparable to gold standards such as polyethyleneimine). Hence, our study clearly demonstrates the importance of the tailor-made GCP anion-binding site for efficient gene transfection. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
    view abstractdoi: 10.1002/cbic.201700433
  • 2017 • 479 Bioactivity and electrochemical behavior of hydroxyapatite-silicon-multi walled carbon nano-tubes composite coatings synthesized by EPD on NiTi alloys in simulated body fluid
    Khalili, V. and Khalil-Allafi, J. and Frenzel, J. and Eggeler, G.
    Materials Science and Engineering C 71 473-482 (2017)
    In order to improve the surface bioactivity of NiTi bone implant and corrosion resistance, hydroxyapatite coating with addition of 20 wt% silicon, 1 wt% multi walled carbon nano-tubes and both of them were deposited on a NiTi substrate using a cathodic electrophoretic method. The apatite formation ability was estimated using immersion test in the simulated body fluid for 10 days. The SEM images of the surface of coatings after immersion in simulated body fluid show that the presence of silicon in the hydroxyapatite coatings accelerates in vitro growth of apatite layer on the coatings. The Open-circuit potential and electrochemical impedance spectroscopy were measured to evaluate the electrochemical behavior of the coatings in the simulated body fluid at 37 °C. The results indicate that the compact structure of hydroxyapatite-20 wt% silicon and hydroxyapatite-20 wt% silicon-1 wt% multi walled carbon nano-tubes coatings could efficiently increase the corrosion resistance of NiTi substrate. © 2016
    view abstractdoi: 10.1016/j.msec.2016.10.036
  • 2017 • 478 Antibacterial activity of microstructured sacrificial anode thin films by combination of silver with platinum group elements (platinum, palladium, iridium)
    Köller, M. and Bellova, P. and Javid, S.M. and Motemani, Y. and Khare, C. and Sengstock, C. and Tschulik, K. and Schildhauer, T.A. and Ludwig, Al.
    Materials Science and Engineering C 74 536-541 (2017)
    Five different Ag dots arrays (16 to 400dots/mm2) were fabricated on a continuous platinum, palladium, or iridium thin film and for comparison also on titanium film by sputter deposition and photolithographic patterning. To analyze the antibacterial activity of these microstructured films Staphylococcus aureus (S. aureus) were placed onto the array surfaces and cultivated overnight. To analyze the viability of planktonic as well as surface adherent bacteria, the applied bacterial fluid was subsequently aspirated, plated on blood agar plates and adherent bacteria were detected by fluorescence microscopy. A particular antibacterial effect towards . S. aureus was induced by Ag dot arrays on each of the platinum group thin film (sacrificial anode system for Ag) in contrast to Ag dot arrays fabricated on the Ti thin films (non-sacrificial anode system for Ag). Among platinum group elements the Ir-Ag system exerted the highest antibacterial activity which was accompanied by most advanced dissolution of the Ag dots and Ag ion release compared to Ag dots on Pt or Pd. © 2016 Elsevier B.V.
    view abstractdoi: 10.1016/j.msec.2016.12.075
  • 2017 • 477 Antibodies under pressure: A Small-Angle X-ray Scattering study of Immunoglobulin G under high hydrostatic pressure
    König, N. and Paulus, M. and Julius, K. and Schulze, J. and Voetz, M. and Tolan, M.
    Biophysical Chemistry 231 45-49 (2017)
    In the present work two subclasses of the human antibody Immunoglobulin G (IgG) have been investigated by Small-Angle X-ray Scattering under high hydrostatic pressures up to 5kbar. It is shown that IgG adopts a symmetric T-shape in solution which differs significantly from available crystal structures. Moreover, high-pressure experiments verify the high stability of the IgG molecule. It is not unfolded by hydrostatic pressures of up to 5kbar but a slight increase of the radius of gyration was observed at elevated pressures. © 2017 Elsevier B.V.
    view abstractdoi: 10.1016/j.bpc.2017.05.016
  • 2017 • 476 Delivery of the autofluorescent protein Rphycoerythrin by calcium phosphate nanoparticles into four different eukaryotic cell lines (HeLa, HEK293T, MG-63, MC3T3): Highly efficient, but leading to endolysosomal proteolysis in HeLa and MC3T3 cells
    Kopp, M. and Rotan, O. and Papadopoulos, C. and Schulze, N. and Meyer, H. and Epple, M.
    PLoS ONE 12 (2017)
    Nanoparticles can be used as carriers to transport biomolecules like proteins and synthetic molecules across the cell membrane because many molecules are not able to cross the cell membrane on their own. The uptake of nanoparticles together with their cargo typically occurs via endocytosis, raising concerns about the possible degradation of the cargo in the endolysosomal system. As the tracking of a dye-labelled protein during cellular uptake and processing is not indicative of the presence of the protein itself but only for the fluorescent label, a label-free tracking was performed with the red-fluorescing model protein R-phycoerythrin (R-PE). Four different eukaryotic cell lines were investigated: HeLa, HEK293T, MG-63, and MC3T3. Alone, the protein was not taken up by any cell line; only with the help of calcium phosphate nanoparticles, an efficient uptake occurred. After the uptake into HeLa cells, the protein was found in early endosomes (shown by the marker EEA1) and lysosomes (shown by the marker Lamp1). There, it was still intact and functional (i.e. properly folded) as its red fluorescence was detected. However, a few hours after the uptake, proteolysis started as indicated by the decreasing red fluorescence intensity in the case of HeLa and MC3T3 cells. 12 h after the uptake, the protein was almost completely degraded in HeLa cells and MC3T3 cells. In HEK293T cells and MG-63 cells, no degradation of the protein was observed. In the presence of Bafilomycin A1, an inhibitor of acidification and protein degradation in lysosomes, the fluorescence of R-PE remained intact over the whole observation period in the four cell lines. These results indicate that despite an efficient nanoparticle-mediated uptake of proteins by cells, a rapid endolysosomal degradation may prevent the desired (e.g. therapeutic) effect of a protein inside a cell. © 2017 Kopp et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
    view abstractdoi: 10.1371/journal.pone.0178260
  • 2017 • 475 Solubilization of proteins in aqueous two-phase extraction through combinations of phase-formers and displacement agents
    Kress, C. and Sadowski, G. and Brandenbusch, C.
    European Journal of Pharmaceutics and Biopharmaceutics 112 38-44 (2017)
    The aqueous two-phase extraction (ATPE) of therapeutic proteins is a promising separation alternative to cost-intensive chromatography, still being the workhorse of nowadays downstream processing. As shown in many publications, using NaCl as displacement agent in salt-polymer ATPE allows for a selective purification of the target protein immunoglobulin G (IgG) from human serum albumin (HSA, represents the impurity). However a high yield of the target protein is only achievable as long as the protein is stabilized in solution and not precipitated. In this work the combined influence of NaCl and polyethylene glycol (Mw = 2000 g/mol) on the IgG-IgG interactions was determined using composition gradient multi-angle light scattering (CG-MALS) demonstrating that NaCl induces a solubilization of IgG in polyethylene glycol 2000 solution. Moreover it is shown that the displacement agent NaCl has a significant and beneficial influence on the IgG solubility in polyethylene glycol 2000-citrate aqueous two-phase system (ATPS) which can also be accessed by these advanced B22 measurements. By simultaneous consideration of IgG solubility data with results of the ATPS phase behavior (especially volume fraction of the respective phases) allows for the selection of process tailored ATPS including identification of the maximum protein feed concentration. Through this approach an ATPS optimization is accessible providing high yields and selectivity of the target protein (IgG). © 2016 Elsevier B.V.
    view abstractdoi: 10.1016/j.ejpb.2016.11.016
  • 2017 • 474 Nanoarmored Enzymes for Organic Enzymology: Synthesis and Characterization of Poly(2-Alkyloxazoline)–Enzyme Conjugates
    Leurs, M. and Tiller, J.C.
    Methods in Enzymology 590 413-444 (2017)
    The properties of enzymes can be altered significantly by modification with polymers. Numerous different methods are known to obtain such polymer–enzyme conjugates (PECs). However, there is no universal method to render enzymes into PECs that are fully soluble in organic solvents. Here, we present a method, which achieves such high degree of modification of proteins that the majority of modified enzymes will be soluble in organic solvents. This is achieved by preparing poly(2-alkyloxazoline)s (POx) with an NH2 end group and coupling this functional polymer via pyromellitic acid dianhydride onto the amino groups of the respective protein. The resulting PECs are capable of serving as surfactants for unmodified proteins, rendering the whole mixture organosoluble. Depending on the nature of the POx and the molecular weight and the nature of the enzyme, the PECs are soluble in chloroform or even toluene. Another advantage of this method is that the poly(2-alkyloxazoline) can be activated with the coupling agent and used for the enzyme conjugation without further purification. The POx–enzyme conjugates generated by this modification strategy show modulated catalytic activity in both, aqueous and organic, systems. © 2017 Elsevier Inc.
    view abstractdoi: 10.1016/bs.mie.2017.01.008
  • 2017 • 473 Black Magic in Gray Titania: Noble-Metal-Free Photocatalytic H2 Evolution from Hydrogenated Anatase
    Liu, N. and Zhou, X. and Nguyen, N.T. and Peters, K. and Zoller, F. and Hwang, I. and Schneider, C. and Miehlich, M.E. and Freitag, D. and Meyer, K. and Fattakhova-Rohlfing, D. and Schmuki, P.
    ChemSusChem 10 62-67 (2017)
    ‘Black’ TiO2—in the widest sense, TiO2 reduced by various treatments—has attracted tremendous scientific interest in recent years because of some outstanding properties; most remarkably in photocatalysis. While the material effects visible light absorption (the blacker, the better), black titania produced by high pressure hydrogenation was recently reported to show another highly interesting feature; noble-metal-free photocatalytic H2 generation. In a systematic investigation of high-temperature hydrogen treatments of anatase nanoparticles, TEM, XRD, EPR, XPS, and photoelectrochemistry are used to characterize different degrees of surface hydrogenation, surface termination, electrical conductivity, and structural defects in the differently treated materials. The materials’ intrinsic activity for photocatalytic hydrogen evolution is coupled neither with their visible light absorption behavior nor the formation of amorphous material, but rather must be ascribed to optimized and specific defect formation (gray is better than black). This finding is further confirmed by using a mesoporous anatase matrix as a hydrogenation precursor, which, after conversion to the gray state, even further enhances the overall photocatalytic hydrogen evolution activity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
    view abstractdoi: 10.1002/cssc.201601264
  • 2017 • 472 Amorphous-amorphous phase separation in API/polymer formulations
    Luebbert, C. and Huxoll, F. and Sadowski, G. and Van Den Mooter, G. and Grohganz, H.
    Molecules 22 (2017)
    The long-term stability of pharmaceutical formulations of poorly-soluble drugs in polymers determines their bioavailability and therapeutic applicability. However, these formulations do not only often tend to crystallize during storage, but also tend to undergo unwanted amorphous-amorphous phase separations (APS). Whereas the crystallization behavior of APIs in polymers has been measured and modeled during the last years, the APS phenomenon is still poorly understood. In this study, the crystallization behavior, APS, and glass-transition temperatures formulations of ibuprofen and felodipine in polymeric PLGA excipients exhibiting different ratios of lactic acid and glycolic acid monomers in the PLGA chain were investigated by means of hot-stage microscopy and DSC. APS and recrystallization was observed in ibuprofen/PLGA formulations, while only recrystallization occurred in felodipine/PLGA formulations. Based on a successful modeling of the crystallization behavior using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT), the occurrence of APS was predicted in agreement with experimental findings. © 2017 by the authors; licensee MDPI, Basel, Switzerland.
    view abstractdoi: 10.3390/molecules22020296
  • 2017 • 471 A metal-free fluorescence turn-on molecular probe for detection of nucleoside triphosphates
    Maity, D. and Li, M. and Ehlers, M. and Schmuck, C.
    Chemical Communications 53 208-211 (2017)
    We report a fluorescence probe 1, which contains a naphthalimide fluorophore with two symmetric peptidic arms equipped with a tailor-made anion-binding motif, the guanidiniocarbonyl pyrrole moiety, for the detection of nucleoside triphosphates. Upon binding to nucleoside triphosphates, especially ATP, 1 shows significant turn-on fluorescence response. Probe 1 can also be applied for the imaging of ATP in cells. © The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c6cc08386b
  • 2017 • 470 Irregular model DNA particles self-assemble into a regular structure
    Preisler, Z. and Saccà, B. and Whitelam, S.
    Soft Matter 13 8894-8902 (2017)
    DNA nanoparticles with three-fold coordination have been observed to self-assemble in experiment into a network equivalent to the hexagonal (6.6.6) tiling, and a network equivalent to the 4.8.8 Archimedean tiling. Both networks are built from a single type of vertex. Here we use analytic theory and equilibrium and dynamic simulation to show that a model particle, whose rotational properties lie between those of the vertices of the 6.6.6 and 4.8.8 networks, can self-assemble into a network built from three types of vertex. Important in forming this network is the ability of the particle to rotate when bound, thereby allowing the formation of more than one type of binding motif. The network in question is equivalent to a false tiling, a periodic structure built from irregular polygons, and possesses 40 particles in its unit cell. The emergence of this complex structure, whose symmetry properties are not obviously related to those of its constituent particles, highlights the potential for creating new structures from simple variants of existing nanoparticles. © 2017 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c7sm01627a
  • 2017 • 469 Enzymatic mineralization generates ultrastiff and tough hydrogels with tunable mechanics
    Rauner, N. and Meuris, M. and Zoric, M. and Tiller, J.C.
    Nature 543 407-410 (2017)
    The cartilage and skin of animals, which are made up of more than fifty per cent water, are rather stiff (having elastic moduli of up to 100 megapascals) as well as tough and hard to break (with fracture energies of up to 9,000 joules per square metre). Such features make these biological materials mechanically superior to existing synthetic hydrogels. Lately, progress has been made in synthesizing tough hydrogels, with double-network hydrogels achieving the toughness of skin and inorganic-organic composites showing even better performance. However, these materials owe their toughness to high stretchability; in terms of stiffness, synthetic hydrogels cannot compete with their natural counterparts, with the best examples having elastic moduli of just 10 megapascals or less. Previously, we described the enzyme-induced precipitation and crystallization of hydrogels containing calcium carbonate, but the resulting materials were brittle. Here we report the enzyme-induced formation of amorphous calcium phosphate nanostructures that are homogenously distributed within polymer hydrogels. Our best materials have fracture energies of 1,300 joules per square metre even in their fully water-swollen state - a value superior to that of most known water-swollen synthetic materials. We are also able to modulate their stiffness up to 440 megapascals, well beyond that of cartilage and skin. Furthermore, the highly filled composite materials can be designed to be optically transparent and to retain most of their stretchability even when notched. We show that percolation drives the mechanical properties, particularly the high stiffness, of our uniformly mineralized hydrogels. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
    view abstractdoi: 10.1038/nature21392
  • 2017 • 468 Poly(2-oxazoline)-Antibiotic Conjugates with Penicillins
    Schmidt, M. and Bast, L.K. and Lanfer, F. and Richter, L. and Hennes, E. and Seymen, R. and Krumm, C. and Tiller, J.C.
    Bioconjugate Chemistry 28 2440-2451 (2017)
    The conjugation of antibiotics with polymers is rarely done, but it might be a promising alternative to low-molecular-weight derivatization. The two penicillins penicillin G (PenG) and penicillin V (PenV) were attached to the end groups of different water-soluble poly(2-oxazoline)s (POx) via their carboxylic acid function. This ester group was shown to be more stable against hydrolysis than the β-lactam ring of the penicillins. The conjugates are still antimicrobially active and up to 20 times more stable against penicillinase catalyzed hydrolysis. The antibiotic activity of the conjugates against Staphylococcus aureus in the presence of penicillinase is up to 350 times higher compared with the free antibiotics. Conjugates with a second antimicrobial function, a dodecyltrimethylammonium group (DDA-X), at the starting end of the PenG and PenV POx conjugates are more antimicrobially active than the conjugates without DDA-X and show high activity in the presence of penicillinase. For example, the conjugates DDA-X-PEtOx-PenG and DDA-X-PEtOx-PenV are 200 to 350 times more active against S. aureus in the presence of penicillinase and almost as effective as the penicillinase stable cloxacollin (Clox) under these conditions. These conjugates show even greater activity compared to cloxacollin without this enzyme present. Further, both conjugates kill Escherichia coli more effectively than PenG and Clox. © 2017 American Chemical Society.
    view abstractdoi: 10.1021/acs.bioconjchem.7b00424
  • 2017 • 467 Indazole-Based Covalent Inhibitors To Target Drug-Resistant Epidermal Growth Factor Receptor
    Tomassi, S. and Lategahn, J. and Engel, J. and Keul, M. and Tumbrink, H.L. and Ketzer, J. and Mühlenberg, T. and Baumann, M. and Schultz-Fademrecht, C. and Bauer, S. and Rauh, D.
    Journal of Medicinal Chemistry 60 2361-2372 (2017)
    The specific targeting of oncogenic mutant epidermal growth factor receptor (EGFR) is a breakthrough in targeted cancer therapy and marks a drastic change in the treatment of non-small cell lung cancer (NSCLC). The recurrent emergence of resistance to these targeted drugs requires the development of novel chemical entities that efficiently inhibit drug-resistant EGFR. Herein, we report the optimization process for a hit compound that has emerged from a phenotypic screen resulting in indazole-based compounds. These inhibitors are conformationally less flexible, target gatekeeper mutated drug-resistant EGFR-L858R/T790M, and covalently alkylate Cys797. Western blot analysis, as well as characterization of the binding kinetics and kinase selectivity profiling, substantiates our approach of targeting drug-resistant EGFR-L858R/T790M with inhibitors incorporating the indazole as hinge binder. © 2017 American Chemical Society.
    view abstractdoi: 10.1021/acs.jmedchem.6b01626
  • 2017 • 466 Functionality of albumin-derived perfluorocarbon-based artificial oxygen carriers in the Langendorff-heart
    Wrobeln, A. and Schlüter, K.D. and Linders, J. and Zähres, M. and Mayer, C. and Kirsch, M. and Ferenz, K.B.
    Artificial Cells, Nanomedicine and Biotechnology 45 723-730 (2017)
    The aim of this study was to prove whether albumin-derived perfluorocarbon-based nanoparticles (capsules) can operate as a novel artificial oxygen carrier in a rat Langendorff-heart perfusion model. Hearts perfused with capsules showed increased left ventricular pressure and rate pressure product compared to hearts perfused with pure Krebs–Henseleit (KH)-buffer. The capsules prevented the myocardium from functional fail when in their absence a noxious ischemia was observed. Capsules did not change rheological properties of KH-buffer and could repeatedly reload with oxygen. This albumin-derived perfluorocarbon-based artificial oxygen carrier preserved the function of rat hearts due to the transport of oxygen in a satisfactory manner. Because of these positive results, the functionality of the applied capsules should be verified in living animals. © 2017 Informa UK Limited, trading as Taylor & Francis Group
    view abstractdoi: 10.1080/21691401.2017.1284858
  • 2017 • 465 Synergistic Effect of Cobalt and Iron in Layered Double Hydroxide Catalysts for the Oxygen Evolution Reaction
    Yang, F. and Sliozberg, K. and Sinev, I. and Antoni, H. and Bähr, A. and Ollegott, K. and Xia, W. and Masa, J. and Grünert, W. and Cuenya, B.R. and Schuhmann, W. and Muhler, M.
    ChemSusChem 10 156-165 (2017)
    Co-based layered double hydroxide (LDH) catalysts with Fe and Al contents in the range of 15 to 45 at % were synthesized by an efficient coprecipitation method. In these catalysts, Fe3+ or Al3+ ions play an essential role as trivalent species to stabilize the LDH structure. The obtained catalysts were characterized by a comprehensive combination of surface- and bulk-sensitive techniques and were evaluated for the oxygen evolution reaction (OER) on rotating disk electrodes. The OER activity decreased upon increasing the Al content for the Co- and Al-based LDH catalysts, whereas a synergistic effect in Co- and Fe-based LDHs was observed, which resulted in an optimal Fe content of 35 at %. This catalyst was spray-coated on Ni foam electrodes and showed very good stability in a flow-through cell with a potential of approximately 1.53 V at 10 mA cm−2 in 1 m KOH for at least 48 h. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
    view abstractdoi: 10.1002/cssc.201601272
  • 2017 • 464 In Vivo Detoxification of Lipopolysaccharide by Antimicrobial Peptides
    Zhang, W. and He, J. and Wu, J. and Schmuck, C.
    Bioconjugate Chemistry 28 319-324 (2017)
    Abundant lipopolysaccharide (LPS) can result in sepsis and septic shock, indicating a serious Gram-negative bacterial contamination. We have developed a novel strategy based on dendritic antimicrobial peptides that can detoxify LPS. The dendritic antimicrobial peptides bind to LPS at the surface of Gram-negative bacteria, killing the bacteria but removing the LPS from the cell wall of dead Gram-negative bacteria, hence detoxifying pathogenic bacteria in its host cells and effectively improving survival of animals infected with Pseudomonas aeruginosa. Our findings provide a way to detoxify bacterial contamination. © 2016 American Chemical Society.
    view abstractdoi: 10.1021/acs.bioconjchem.6b00664
  • 2017 • 463 Mineral in skeletal elements of the terrestrial crustacean Porcellio scaber: SRμCT of function related distribution and changes during the moult cycle
    Ziegler, A. and Neues, F. and Janáček, J. and Beckmann, F. and Epple, M.
    Arthropod Structure and Development 46 63-76 (2017)
    Terrestrial isopods moult first the posterior and then the anterior half of the body, allowing for storage and recycling of CaCO3. We used synchrotron-radiation microtomography to estimate mineral content within skeletal segments in sequential moulting stages of Porcellio scaber. The results suggest that all examined cuticular segments contribute to storage and recycling, however, to varying extents. The mineral within the hepatopancreas after moult suggests an uptake of mineral from the ingested exuviae. The total maximum loss of mineral was 46% for the anterior and 43% for the posterior cuticle. The time course of resorption of mineral and mineralisation of the new cuticle suggests storage and recycling of mineral in the posterior and anterior cuticle. The mineral in the anterior pereiopods decreases by 25% only. P. scaber has long legs and can run fast; therefore, a less mineralised and thus lightweight cuticle in pereiopods likely serves to lower energy consumption during escape behaviour. Differential demineralisation occurs in the head cuticle, in which the cornea of the complex eyes remains completely mineralised. The partes incisivae of the mandibles are mineralised before the old cuticle is demineralised and shed. Probably, this enables the animal to ingest the old exuviae after each half moult. © 2016 Elsevier Ltd.
    view abstractdoi: 10.1016/j.asd.2016.05.004
  • 2017 • 462 Nanoparticulate versus ionic silver: Behavior in the tank water, bioaccumulation, elimination and subcellular distribution in the freshwater mussel Dreissena polymorpha
    Zimmermann, S. and Ruchter, N. and Loza, K. and Epple, M. and Sures, B.
    Environmental Pollution 222 251-260 (2017)
    Zebra mussels (Dreissena polymorpha) were exposed to polyvinylpyrrolidone (PVP)-coated silver nanoparticles (AgNP; hydrodynamic diameter 80 nm; solid diameter 50 nm) to investigate the behavior of Ag in the tank water with respect to its uptake, bioaccumulation, elimination and subcellular distribution in the mussel soft tissue. Parallel experiments were performed with ionic Ag (AgNO3) to unravel possible differences between the metal forms. The recovery of the applied Ag concentration (500 μg/L) in the tank water was clearly affected by the metal source (AgNP < AgNO3) and water type (reconstituted water < tap water). Filtration (< 0.45 μm) of water samples showed different effects on the quantified metal concentration depending on the water type and Ag form. Ag accumulation in the mussel soft tissue was neither influenced by the metal source nor by the water type. Ag concentrations in the mussel soft tissue did not decrease during 14 days of depuration. For both metal forms the Ag distribution within different subcellular fractions, i.e. metal-rich granules (MRG), cellular debris, organelles, heat-sensitive proteins (HSP) and metallothionein-like proteins (MTLP), revealed time-dependent changes which can be referred to intracellular Ag translocation processes. The results provide clear evidence for the uptake of Ag by the mussel soft tissue in nanoparticulate as well as in ionic form. Thus, zebra mussels could be used as effective accumulation indicators for environmental monitoring of both Ag forms. © 2016 Elsevier Ltd.
    view abstractdoi: 10.1016/j.envpol.2016.12.048
  • 2017 • 461 Peculiarities in thermal evolution of precipitated amorphous calcium phosphates with an initial Ca/P ratio of 1:1
    Zyman, Z. and Epple, M. and Goncharenko, A. and Rokhmistrov, D. and Prymak, O. and Loza, K.
    Journal of Materials Science: Materials in Medicine 28 (2017)
    Thermal evolution of amorphous calcium phosphate (ACP) powder from a fast nitrate synthesis with a Ca/P ratio of 1:1 were studied in the range of 20–980 °C. The powder consisted of amorphous dicalcium phosphate anhydrate (CaHPO4) after heating to 200 °C. CaHPO4 gradually condensed to amorphous calcium pyrophosphate Ca2P2O7 (CPP) between 200 to 620 °C. Amorphous CPP crystallized at 620–740 °C to a metastable polymorph α′-CPP of the high-temperature phase α-CPP and β-CPP. The α′-CPP/ β-CPP phase ratio reached a maximum at 800 °C (60 wt% α′-CPP/40 wt% β-CPP), and α′-CPP gradually transformed to β-CPP at a higher temperature. Some β-TCP occurred at 900 °C, so that a three-phasic mixture was obtained in the powder heated to 980 °C. The occurrence of metastable α′-CPP is attributed to Ostwald’s step rule, and a mechanism for β-TCP formation is proposed. The advantages of prospective biomaterials from these powders are discussed. © 2017, Springer Science+Business Media New York.
    view abstractdoi: 10.1007/s10856-016-5820-4
  • 2016 • 460 Electrophoretic deposition of ligand-free platinum nanoparticles on neural electrodes affects their impedance in vitro and in vivo with no negative effect on reactive gliosis
    Angelov, S.D. and Koenen, S. and Jakobi, J. and Heissler, H.E. and Alam, M. and Schwabe, K. and Barcikowski, S. and Krauss, J.K.
    Journal of Nanobiotechnology 14 (2016)
    Background: Electrodes for neural stimulation and recording are used for the treatment of neurological disorders. Their features critically depend on impedance and interaction with brain tissue. The effect of surface modification on electrode impedance was examined in vitro and in vivo after intracranial implantation in rats. Electrodes coated by electrophoretic deposition with platinum nanoparticles (NP; <10 and 50 nm) as well as uncoated references were implanted into the rat's subthalamic nucleus. After postoperative recovery, rats were electrostimulated for 3 weeks. Impedance was measured before implantation, after recovery and then weekly during stimulation. Finally, local field potential was recorded and tissue-to-implant reaction was immunohistochemically studied. Results: Coating with NP significantly increased electrode's impedance in vitro. Postoperatively, the impedance of all electrodes was temporarily further increased. This effect was lowest for the electrodes coated with particles <10 nm, which also showed the most stable impedance dynamics during stimulation for 3 weeks and the lowest total power of local field potential during neuronal activity recording. Histological analysis revealed that NP-coating did not affect glial reactions or neural cell-count. Conclusions: Coating with NP <10 nm may improve electrode's impedance stability without affecting biocompatibility. Increased impedance after NP-coating may improve neural recording due to better signal-to-noise ratio. © 2016 Angelov et al.
    view abstractdoi: 10.1186/s12951-015-0154-9
  • 2016 • 459 Resistance of Amphiphilic Polysaccharides against Marine Fouling Organisms
    Bauer, S. and Alles, M. and Arpa-Sancet, M.P. and Ralston, E. and Swain, G.W. and Aldred, N. and Clare, A.S. and Finlay, J.A. and Callow, M.E. and Callow, J.A. and Rosenhahn, A.
    Biomacromolecules 17 897-904 (2016)
    Amphiphilic coatings are promising candidates for fouling-release applications. As hydrophilic components, polysaccharides are interesting and environmentally benign building blocks. We used covalently coupled alginic acid (AA) and hyaluronic acid (HA) and postmodified them with a hydrophobic fluorinated amine. The surfaces showed good stability under marine conditions and fluorination led to a decreased uptake of Ca2+ ions after modification. In single species settlement assays (bacteria, diatoms, barnacle cypris larvae), the modification decreased the settlement density and/or the adhesion strength of many of the tested species. Field studies supported findings of the laboratory experiments, as hydrophobic modification of AA and HA decreased diatom colonization. © 2016 American Chemical Society.
    view abstractdoi: 10.1021/acs.biomac.5b01590
  • 2016 • 458 Monitoring Conformational Changes in the Receptor Tyrosine Kinase EGFR
    Becker, C. and Öcal, S. and Nguyen, H.D. and Phan, T. and Keul, M. and Simard, J.R. and Rauh, D.
    ChemBioChem 17 990-994 (2016)
    The receptor tyrosine kinase EGFR is regulated by complex conformational changes, and this conformational control is disturbed in certain types of cancer. Many ligands are known to bind EGFR in its active conformation, thereby preventing ATP from binding. Only a few ligands are known to stabilize EGFR in its inactive conformation, thus providing novel strategies for perturbing EGFR activity. We report a direct binding assay that enables the identification of novel ligands that bind to and stabilize the inactive conformation of EGFR. Too active? Stabilize the inactive conformation. EGFR is a target for tumor therapy, with many small molecules known to bind its kinase domain in the active conformation. A binding assay was developed to search for ligands stabilizing its inactive conformation, thus providing a tool for new approaches to target its dynamic regulatory mechanisms. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cbic.201600115
  • 2016 • 457 Zintl clusters as wet-chemical precursors for germanium nanomorphologies with tunable composition
    Bentlohner, M.M. and Waibel, M. and Zeller, P. and Sarkar, K. and Müller-Buschbaum, P. and Fattakhova-Rohlfing, D. and Fässler, T.F.
    Angewandte Chemie - International Edition 55 2441-2445 (2016)
    [Ge9]4- Zintl clusters are used as soluble germanium source for a bottom-up fabrication of Ge nanomorphologies such as inverse opal structures with tunable composition. The method is based on the assembly and oxidation of [Ge9]4- clusters in a template mold using SiCl4, GeCl4, and PCl3 leading to Si and P-containing Ge phases as shown by X-ray diffraction, Raman spectroscopy, and energy-dispersive X-ray analysis. [Ge9]4- clusters are retained using ethylenediamine (en) as a transfer medium to a mold after removal of the solvent if water is thoroughly excluded, but are oxidized to amorphous Ge in presence of water traces. 1H NMR spectroscopy reveals the oxidative deprotonation of en by [Ge9]4-. Subsequent annealing leads to crystalline Ge. As an example for wet-chemical synthesis of complex Ge nanomorphologies, we describe the fabrication of undoped and P-doped inverse opal-structured Ge films with a rather low oxygen contents. The morphology of the films with regular volume porosity is characterized by SEM, TEM, and grazing incidence small-angle X-ray scattering. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201508246
  • 2016 • 456 Dual-Templated Cobalt Oxide for Photochemical Water Oxidation
    Deng, X. and Bongard, H.-J. and Chan, C.K. and Tüysüz, H.
    ChemSusChem 9 409-415 (2016)
    Mesoporous Co3O4 was prepared using a dual templating approach whereby mesopores inside SiO2 nanospheres, as well as the void spaces between the nanospheres, were used as templates. The effect of calcination temperature on the crystallinity, morphology, and textural parameters of the Co3O4 replica was investigated. The catalytic activity of Co3O4 for photochemical water oxidation in a [Ru(bpy)3]2+[S2O8]2- system was evaluated. The Co3O4 replica calcined at the lowest temperature (150°C) exhibited the best performance as a result of the unique nanostructure and high surface area arising from the dual templating. The performance of Co3O4 with highest surface area was further examined in electrochemical water oxidation. Superior activity over high temperature counterpart and decent stability was observed. Furthermore, CoO with identical morphology was prepared from Co3O4 using an ethanol reduction method and a higher turnover-frequency number for photochemical water oxidation was obtained. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.201500872
  • 2016 • 455 Improved Antifouling Properties of Polydimethylsiloxane Films via Formation of Polysiloxane/Polyzwitterion Interpenetrating Networks
    Dundua, A. and Franzka, S. and Ulbricht, M.
    Macromolecular Rapid Communications 37 2030-2036 (2016)
    Nonspecific adsorption of proteins is a challenging problem for the development of biocompatible materials, as well as for antifouling and fouling-release coatings, for instance for the marine industry. The concept of preparing amphiphilic systems based on low surface energy hydrophobic materials via their hydrophilic modification is being widely pursued. This work describes a novel two-step route for the preparation of interpenetrating polymer networks of otherwise incompatible poly(dimethylsiloxane) and zwitterionic polymers. Changes in surface hydrophilicity as well as surface charge at different pH values are investigated. Characterization using atomic force microscopy provides thorough insight into surface changes upon hydrophilic modification. Protein fouling of the materials is assessed using fibrinogen as a model protein. (Figure presented.). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
    view abstractdoi: 10.1002/marc.201600473
  • 2016 • 454 Permeability profile of poly(alkyl cyanoacrylate) nanocapsules
    Erdmann, C. and Mayer, C.
    Journal of Colloid and Interface Science 478 394-401 (2016)
    The permeability profile of poly(alkyl cyanoacrylate) nanocapsules is studied using pulsed-field gradient NMR on a variety of tracer molecules of different size and polarity. In addition, the influence of the surfactant layer and of organic tracer molecules on the capsule membrane permeability for water is examined. The aim of the study is a detailed understanding of the dependencies between molecular properties of a given tracer and its capability to permeate the polymer membrane. As expected, the results clearly show that the capsule membrane permeability depends on the size of the tracer molecule: the exchange rate of polyethylene glycols continuously decreases with increasing chain length. However, the permeation rate also varies with the polarity of the tracer molecule: molecules of lower polarity exchange faster than more polar ones. In turn, the capsule membrane permeability is influenced by added organic compounds. Focusing on water as a characteristic permeate and depending on the type of the additive, the permeability can be varied by almost an order of magnitude, offering an opportunity to reversibly switch the uptake and release properties of the capsules. © 2016 Elsevier Inc.
    view abstractdoi: 10.1016/j.jcis.2016.06.034
  • 2016 • 453 Colonic gene silencing using siRNA-loaded calcium phosphate/PLGA nanoparticles ameliorates intestinal inflammation in vivo
    Frede, A. and Neuhaus, B. and Klopfleisch, R. and Walker, C. and Buer, J. and Müller, W. and Epple, M. and Westendorf, A.M.
    Journal of Controlled Release 222 86-96 (2016)
    Cytokines and chemokines are predominant players in the progression of inflammatory bowel diseases. While systemic neutralization of these players with antibodies works well in some patients, serious contraindications and side effects have been reported. Therefore, the local interference of cytokine signaling mediated by siRNA-loaded nanoparticles might be a promising new therapeutic approach. In this study, we produced multi-shell nanoparticles consisting of a calcium phosphate (CaP) core coated with siRNA directed against pro-inflammatory mediators, encapsulated into poly(d,l-lactide-co-glycolide acid) (PLGA), and coated with a final outer layer of polyethyleneimine (PEI), for the local therapeutic treatment of colonic inflammation. In cell culture, siRNA-loaded CaP/PLGA nanoparticles exhibited a rapid cellular uptake, almost no toxicity, and an excellent in vitro gene silencing efficiency. Importantly, intrarectal application of these nanoparticles loaded with siRNA directed against TNF-α, KC or IP-10 to mice suffering from dextran sulfate sodium (DSS)-induced colonic inflammation led to a significant decrease of the target genes in colonic biopsies and mesenteric lymph nodes which was accompanied with a distinct amelioration of intestinal inflammation. Thus, this study provides evidence that the specific and local modulation of the inflammatory response by CaP/PLGA nanoparticle-mediated siRNA delivery could be a promising approach for the treatment of intestinal inflammation. © 2015 Elsevier B.V. All rights reserved.
    view abstractdoi: 10.1016/j.jconrel.2015.12.021
  • 2016 • 452 Electrochemical bromination of organosulfur containing species for the determination of the strength of garlic (A. sativum)
    Hall, E.M. and Tschulik, K. and Batchelor-McAuley, C. and Compton, R.G.
    Food Chemistry 199 817-821 (2016)
    The extraction by ethyl acetate and subsequent electrochemical detection of organosulfur containing molecules from garlic is demonstrated. The electrochemical results first evidence the high sensitivity of the process towards the model compound propyl disulfide. Through the in situ formation of bromine at a platinum electrode the propyl disulfide can be readily detected at concentrations as low as 12.5 μM. Second, the work focuses on the detection of organosulfur from fresh garlic samples. Extraction of the organosulfur 'flavour' molecules is achieved with ethyl acetate. Addition of this extract to the electrochemical cell results in an analytically useful signal allowing the voltammetric peak height to be successfully correlated with the garlic strength, as measured using an organoleptic tasting panel. © 2015 Elsevier Ltd. All rights reserved.
    view abstractdoi: 10.1016/j.foodchem.2015.12.086
  • 2016 • 451 Catch bond interaction allows cells to attach to strongly hydrated interfaces
    Hanke-Roos, M. and Meseck, G.R. and Rosenhahn, A.
    Biointerphases 11 1-8 (2016)
    Hyaluronans are a class of glycosaminoglycans that are widespread in the mammalian body and serve a variety of functions. Their most striking characteristic is their pronounced hydrophilicity and their capability to inhibit unspecific adhesion when present at interfaces. Catch-bond interactions are used by the CD44 receptor to interact with this inert material and to roll on the surfaces coated with hyaluronans. In this minireview, the authors discuss the general properties of hyaluronans and the occurrence and relevance of the CD44 catch-bond interaction in the context of hematopoiesis, cancer development, and leukemia. © 2016 American Vacuum Society.
    view abstractdoi: 10.1116/1.4939040
  • 2016 • 450 Thermodynamics of Bioreactions
    Held, C. and Sadowski, G.
    Annual Review of Chemical and Biomolecular Engineering 7 395-414 (2016)
    Thermodynamic principles have been applied to enzyme-catalyzed reactions since the beginning of the 1930s in an attempt to understand metabolic pathways. Currently, thermodynamics is also applied to the design and analysis of biotechnological processes. The key thermodynamic quantity is the Gibbs energy of reaction, which must be negative for a reaction to occur spontaneously. However, the application of thermodynamic feasibility studies sometimes yields positive Gibbs energies of reaction even for reactions that are known to occur spontaneously, such as glycolysis. This article reviews the application of thermodynamics in enzyme-catalyzed reactions. It summarizes the basic thermodynamic relationships used for describing the Gibbs energy of reaction and also refers to the nonuniform application of these relationships in the literature. The review summarizes state-of-the-art approaches that describe the influence of temperature, pH, electrolytes, solvents, and concentrations of reacting agents on the Gibbs energy of reaction and, therefore, on the feasibility and yield of biological reactions. Copyright © 2016 by Annual Reviews. All rights reserved.
    view abstractdoi: 10.1146/annurev-chembioeng-080615-034704
  • 2016 • 449 Non-monotonic course of protein solubility in aqueous polymer-salt solutions can be modeled using the sol-mxDLVO model
    Herhut, M. and Brandenbusch, C. and Sadowski, G.
    Biotechnology Journal 11 282-289 (2016)
    Protein purification is often performed using cost-intensive chromatographic steps. To discover economic alternatives (e.g., crystallization), knowledge on protein solubility as a function of temperature, pH, and additives in solution as well as their concentration is required. State-of-the-art models for predicting protein solubility almost exclusively consider aqueous salt systems, whereas "salting-in" and "salting-out" effects induced by the presence of an additional polymer are not considered. Thus, we developed the sol-mxDLVO model. Using this newly developed model, protein solubility in the presence of one salt and one polymer, especially the non-monotonic course of protein solubility, could be predicted. Systems considered included salts (NaCl, Na-p-Ts, (NH4)2SO4) and the polymer polyethylene glycol (MW: 2000 g/mol, 12000 g/mol) and proteins lysozyme from chicken egg white (pH 4 to 5.5) and D-xylose ketol-isomerase (pH 7) at 298.15 K. The results show that by using the sol-mxDLVO model, protein solubility in polymer-salt solutions can be modeled in good agreement with the experimental data for both proteins considered. The sol-mxDLVO model can describe the non-monotonic course of protein solubility as a function of polymer concentration and salt concentration, previously not covered by state-of-the-art models. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/biot.201500123
  • 2016 • 448 Inclusion of mPRISM potential for polymer-induced protein interactions enables modeling of second osmotic virial coefficients in aqueous polymer-salt solutions
    Herhut, M. and Brandenbusch, C. and Sadowski, G.
    Biotechnology Journal 11 146-154 (2016)
    The downstream processing of therapeutic proteins is a challenging task. Key information needed to estimate applicable workup strategies (e.g. crystallization) are the interactions of the proteins with other components in solution. This information can be deduced from the second osmotic virial coefficient B22, measurable by static light scattering. Thermodynamic models are very valuable for predicting B22 data for different process conditions and thus decrease the experimental effort. Available B22 models consider aqueous salt solutions but fail for the prediction of B22 if an additional polymer is present in solution. This is due to the fact that depending on the polymer concentration protein-protein interactions are not rectified as assumed within these models. In this work, we developed an extension of the xDLVO model to predict B22 data of proteins in aqueous polymer-salt solutions. To show the broad applicability of the model, lysozyme, γ-globulin and D-xylose ketol isomerase in aqueous salt solution containing polyethylene glycol were considered. For all proteins considered, the modified xDLVO model was able to predict the experimentally observed non-monotonical course in B22 data with high accuracy. When used in an early stage in process development, the model will contribute to an efficient and cost effective downstream processing development. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/biot.201500086
  • 2016 • 447 Design principles for high-pressure force fields: Aqueous TMAO solutions from ambient to kilobar pressures
    Hölzl, C. and Kibies, P. and Imoto, S. and Frach, R. and Suladze, S. and Winter, R. and Marx, D. and Horinek, D. and Kast, S.M.
    Journal of Chemical Physics 144 (2016)
    Accurate force fields are one of the major pillars on which successful molecular dynamics simulations of complex biomolecular processes rest. They have been optimized for ambient conditions, whereas high-pressure simulations become increasingly important in pressure perturbation studies, using pressure as an independent thermodynamic variable. Here, we explore the design of non-polarizable force fields tailored to work well in the realm of kilobar pressures - while avoiding complete reparameterization. Our key is to first compute the pressure-induced electronic and structural response of a solute by combining an integral equation approach to include pressure effects on solvent structure with a quantum-chemical treatment of the solute within the embedded cluster reference interaction site model (EC-RISM) framework. Next, the solute's response to compression is taken into account by introducing pressure-dependence into selected parameters of a well-established force field. In our proof-of-principle study, the full machinery is applied to N,N,N-trimethylamine-N-oxide (TMAO) in water being a potent osmolyte that counteracts pressure denaturation. EC-RISM theory is shown to describe well the charge redistribution upon compression of TMAO(aq) to 10 kbar, which is then embodied in force field molecular dynamics by pressure-dependent partial charges. The performance of the high pressure force field is assessed by comparing to experimental and ab initio molecular dynamics data. Beyond its broad usefulness for designing non-polarizable force fields for extreme thermodynamic conditions, a good description of the pressure-response of solutions is highly recommended when constructing and validating polarizable force fields. © 2016 AIP Publishing LLC.
    view abstractdoi: 10.1063/1.4944991
  • 2016 • 446 A Single Dose of the Anti-Resorptive Peptide Human Calcitonin Paradoxically Augments Particle- and Endotoxin-Mediated Pro-Inflammatory Cytokine Production in Vitro
    Jablonski, H. and Wedemeyer, C. and Bachmann, H.S. and Schlagkamp, M. and Bernstein, A. and Jäger, M. and Kauther, M.D.
    Hormone and Metabolic Research 48 607-612 (2016)
    The peptide hormone calcitonin (CT) is known to inhibit bone resorption and has previously been shown also to prevent particle-induced osteolysis, the leading cause of revision arthroplasty. In the present study, the influence of human CT on the initial inflammatory response to particulate wear debris or bacterial endotoxins, ultimately leading to osteoclast-mediated bone resorption, was analysed in human THP-1 macrophage-like cells. The cells were activated with either ultra-high molecular weight polyethylene (UHMWPE) particles or bacterial lipopolysaccharides (LPS) in order to simulate an osteolysis-associated inflammatory response. The cells were simultaneously treated with human CT (10-9 M). Cytokine production of tumour necrosis factor (TNF)-α was quantified on both RNA and protein levels while interleukins (IL)-1β and IL-6 were measured as secreted protein only. Stimulation of the cells with either particles or LPS led to a dose- and time-dependent increase of TNF-α mRNA production and protein secretion of TNF-α, IL-1β, and IL-6. Application of CT mostly enhanced cytokine production as elicited by UHMWPE particles while a pronounced transient inhibitory effect on LPS-induced inflammation became evident at 24 h of incubation. Human CT displayed ambivalent effects on the wear- and LPS-induced production of pro-inflammatory cytokines. Thereby, the peptide primarily upregulated particle-induced inflammation while LPS-induced cytokine secretion was temporarily attenuated in a distinct manner. It needs to be evaluated whether the pro- or anti-inflammatory action of CT contributes to its known anti-resorptive effects. Thus, the therapeutic potential of the peptide in the treatment of either particle- or endotoxin-mediated bone resorption could be determined.
    view abstractdoi: 10.1055/s-0042-108338
  • 2016 • 445 Barrierless growth of precursor-free, ultrafast laser-fragmented noble metal nanoparticles by colloidal atom clusters - A kinetic in situ study
    Jendrzej, S. and Gökce, B. and Amendola, V. and Barcikowski, S.
    Journal of Colloid and Interface Science 463 299-307 (2016)
    Unintended post-synthesis growth of noble metal colloids caused by excess amounts of reactants or highly reactive atom clusters represents a fundamental problem in colloidal chemistry, affecting product stability or purity. Hence, quantified kinetics could allow defining nanoparticle size determination in dependence of the time. Here, we investigate in situ the growth kinetics of ps pulsed laser-fragmented platinum nanoparticles in presence of naked atom clusters in water without any influence of reducing agents or surfactants. The nanoparticle growth is investigated for platinum covering a time scale of minutes to 50 days after nanoparticle generation, it is also supplemented by results obtained from gold and palladium. Since a minimum atom cluster concentration is exceeded, a significant growth is determined by time resolved UV/Vis spectroscopy, analytical disc centrifugation, zeta potential measurement and transmission electron microscopy. We suggest a decrease of atom cluster concentration over time, since nanoparticles grow at the expense of atom clusters. The growth mechanism during early phase (<1. day) of laser-synthesized colloid is kinetically modeled by rapid barrierless coalescence. The prolonged slow nanoparticle growth is kinetically modeled by a combination of coalescence and Lifshitz-Slyozov-Wagner kinetic for Ostwald ripening, validated experimentally by the temperature dependence of Pt nanoparticle size and growth quenching by Iodide anions. © 2015.
    view abstractdoi: 10.1016/j.jcis.2015.10.032
  • 2016 • 444 Protein partition coefficients can be estimated efficiently by hybrid shortcut calculations
    Kress, C. and Sadowski, G. and Brandenbusch, C.
    Journal of Biotechnology 233 151-159 (2016)
    The extraction of therapeutic proteins like monoclonal antibodies in aqueous two-phase systems (ATPS) is a suitable alternative to common cost intensive chromatographic purification steps within the downstream processing. Thereby the protein partitioning can be selectively changed using a displacement agent (additional salt) in order to allow for a successful purification of the target protein. Within this work a new shortcut strategy for the calculation of protein partition coefficients in polymer-salt ATPS is presented. The required protein-solute (phase-forming component, displacement agent) interactions are covered by the cross virial coefficient B23 measured by composition gradient multi-angle light scattering (CG-MALS). Using this shortcut calculation allows for an efficient determination of the partition coefficients of the target protein immunoglobulin G (IgG) and the impurity human serum albumin (HSA) within PEG-citrate and PEG-phosphate ATPS independently on the protein concentration. We demonstrate that the selection of a suitable displacement agent allowing for a selective purification of IgG from HSA is accessible by B23. Based on the determination of the protein–protein interactions via CG-MALS covered by the second osmotic virial coefficient B22 a further optimization of ATPS preventing protein precipitation is enabled. The results show that our approach contributes to an efficient downstream processing development. © 2016 Elsevier B.V.
    view abstractdoi: 10.1016/j.jbiotec.2016.06.032
  • 2016 • 443 Predicting the solubility of pharmaceutical cocrystals in solvent/anti-solvent mixtures
    Lange, L. and Heisel, S. and Sadowski, G.
    Molecules 21 (2016)
    In this work, the solubilities of pharmaceutical cocrystals in solvent/anti-solvent systems were predicted using PC-SAFT in order to increase the efficiency of cocrystal formation processes. Modeling results and experimental data were compared for the cocrystal system nicotinamide/succinic acid (2:1) in the solvent/anti-solvent mixtures ethanol/water, ethanol/acetonitrile and ethanol/ethyl acetate at 298.15 K and in the ethanol/ethyl acetate mixture also at 310.15 K. The solubility of the investigated cocrystal slightly increased when adding small amounts of anti-solvent to the solvent, but drastically decreased for high anti-solvent amounts. Furthermore, the solubilities of nicotinamide, succinic acid and the cocrystal in the considered solvent/anti-solvent mixtures showed strong deviations from ideal-solution behavior. However, by accounting for the thermodynamic non-ideality of the components, PC-SAFT is able to predict the solubilities in all above-mentioned solvent/anti-solvent systems in good agreement with the experimental data. © 2016 by the authors; licensee MDPI.
    view abstractdoi: 10.3390/molecules21050593
  • 2016 • 442 Micropellet-loaded rods with dose-independent sustained release properties for individual dosing via the Solid Dosage Pen
    Laukamp, E.J. and Knop, K. and Thommes, M. and Breitkreutz, J.
    International Journal of Pharmaceutics 499 271-279 (2016)
    Individual dosing of medicines is relevant for paediatrics, geriatrics and personalised medicine. The Solid Dosage Pen (SDP) allows for individual dosing by cutting monolithic, tablet-like drug carriers of pre-defined heights. The aim of the present study was to develop micropellet-loaded rods (MPLRs) with dose-independent sustained release properties for individual dosing via the Solid Dosage Pen. Therefore, micropellets were successfully layered with carbamazepine and coated with polyvinyl acetate (PVAc) and PVAc/polyvinyl alcohol-polyethylene glycol (PVA-PEG). The tensile strength of the sustained release micropellets (300-450 μm) was more than two times higher (12.6-17.1 MPa) than pressures occurring during ram-extrusion of the MPLRs (below 5.8 MPa). Due to relative crystallinities above 93% for PVAc and PVA-PEG a low solubility of the coating films within the PEG-matrix was observed. The sustained release micropellets were successfully incorporated into MPLRs. Drug release properties of the pellets maintained after embedding into the matrix. Hence, the MPLRs provided dose-independent prolonged drug liberation which was not achieved for drug-loaded rods before. The MPLRs permitted the application of the SDP with a precise drug delivery from individually cut single doses. Storage stability was proven for MPLRs containing PVAc/PVA-PEG coated pellets. In conclusion, the MPLRs combined the advantages of multiparticulate dosage forms with the SDP as a device for individual dosing. © 2016 Elsevier B.V. All rights reserved.
    view abstractdoi: 10.1016/j.ijpharm.2016.01.001
  • 2016 • 441 Incorporation of a Non-Natural Arginine Analogue into a Cyclic Peptide Leads to Formation of Positively Charged Nanofibers Capable of Gene Transfection
    Li, M. and Ehlers, M. and Schlesiger, S. and Zellermann, E. and Knauer, S.K. and Schmuck, C.
    Angewandte Chemie - International Edition 55 598-601 (2016)
    Functionalization of the tetracationic cyclic peptide (Ka)4 with a single guanidiniocarbonyl pyrrole (GCP) moiety, a weakly basic but highly efficient arginine analogue, completely alters the self-assembly properties of the peptide. In contrast to the nonfunctionalized peptide 2, which does not self-assemble, GCP-containing peptide 1 forms cationic nanofibers of micrometer length. These aggregates are efficient gene transfection vectors. DNA binds to their cationic surface and is efficiently delivered into cells. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201508714
  • 2016 • 440 Composites of fluoroapatite and methylmethacrylate-based polymers (PMMA) for biomimetic tooth replacement
    Lübke, A. and Enax, J. and Wey, K. and Fabritius, H.-O. and Raabe, D. and Epple, M.
    Bioinspiration and Biomimetics 11 (2016)
    Synthetic composite materials that mimic the structure and composition of mammalian tooth enamel were prepared by mixing fluoroapatite rods (diameter 2-3 μm, thickness about 0.5 μm) and methylmethacrylate (MMA), followed by polymerization either during or immediately after ultracentrifugation, using either a tertiary amine/radical initiator for polymerization at room temperature or a radical initiator for thermal polymerization. This led to mineral-rich composites (mineral content between 50 and 75 wt%). To enhance the mechanical stability and the interaction between fluoroapatite and polymer matrix, small amounts of differently functionalized MMA monomers were added to the co-monomer mixture. Another approach was the coating of the fluoroapatite rods with silica and the polymerization in the presence of a siloxane-functionalized MMA monomer. The hardness of the composites was about 0.2-0.4 GPa as determined by Vickers indentation tests, about 2 times higher than the polymer matrix alone. The composites had a good resistance against acids (60 min at pH 3, 37 °C). © 2016 IOP Publishing Ltd.
    view abstractdoi: 10.1088/1748-3190/11/3/035001
  • 2016 • 439 Insertion stability of poly(ethylene glycol)-cholesteryl-based lipid anchors in liposome membranes
    Molnar, D. and Linders, J. and Mayer, C. and Schubert, R.
    European Journal of Pharmaceutics and Biopharmaceutics 103 51-61 (2016)
    Liposomes consist of a hydrophilic core surrounded by a phospholipid (PL) bilayer. In human blood, the half-life of such artificial vesicles is limited. To prolong their stability in the circulation, liposomal bilayers can be modified by inserting poly(ethylene glycol) (PEG) molecules using either PL or sterols as membrane anchors. This establishes a hydrophilic steric barrier, reducing the adsorption of serum proteins, recognition and elimination by cells of the immune system. In addition, targeting ligands (such as antibodies) are frequently coupled to the distal end of the PEG chains to direct the vesicles (then called 'immuno-liposomes') to specific cell types, such as tumor cells. To our knowledge, experiments on the stability of ligand anchoring have so far only been conducted with PL-based PEGs and not with sterol-based PEGs after insertion via the sterol-based post-insertion technique (SPIT). Therefore, our study examines the insertion stability of PEG-cholesteryl ester (Chol-PEG) molecules with PEG chains of 1000, 1500 and 2000 Da molecular mass which have been inserted into the membranes of liposomes using SPIT. For this study we used different acceptor media and multiple analytical techniques, including pulsed-field-gradient nuclear magnetic resonance (PFG-NMR), free-flow electrophoresis, size exclusion chromatography and ultracentrifugation. The obtained data consistently showed that a higher molar mass of PEG chains positively correlates with higher release from the liposome membranes. Furthermore, we could detect and quantify the migration of Chol-PEG molecules from radioactively double-labeled surface-modified liposomes to negatively charged acceptor liposomes via free-flow electrophoresis. Insertion of Chol-PEG molecules into the membrane of preformed liposomes using SPIT is an essential step for the functionalization of liposomes with the aim of specific targeting. For the first time, we present a kinetic analysis of this insertion process using PFG-NMR, showing that insertion into the liposomal membranes takes place within 90 s for Chol-PEG1000 molecules. © 2016 Published by Elsevier B.V.
    view abstractdoi: 10.1016/j.ejpb.2016.03.023
  • 2016 • 438 Solid-Supported Lipid Multilayers under High Hydrostatic Pressure
    Nowak, B. and Paulus, M. and Nase, J. and Salmen, P. and Degen, P. and Wirkert, F.J. and Honkimäki, V. and Tolan, M.
    Langmuir 32 2638-2643 (2016)
    In this work, the structure of solid-supported lipid multilayers exposed to increased hydrostatic pressure was studied in situ by X-ray reflectometry at the solid-liquid interface between silicon and an aqueous buffer solution. The layers' vertical structure was analyzed up to a maximum pressure of 4500 bar. The multilayers showed phase transitions from the fluid into different gel phases. With increasing pressure, a gradual filling of the sublayers between the hydrophilic head groups with water was observed. This process was inverted when the pressure was decreased, yielding finally smaller water layers than those in the initial state. As is commonly known, water has an abrasive effect on lipid multilayers by the formation of vesicles. We show that increasing pressure can reverse this process so that a controlled switching between multi- and bilayers is possible. © 2016 American Chemical Society.
    view abstractdoi: 10.1021/acs.langmuir.5b04554
  • 2016 • 437 A microstructurally based continuum model of cartilage viscoelasticity and permeability incorporating measured statistical fiber orientations
    Pierce, D.M. and Unterberger, M.J. and Trobin, W. and Ricken, T. and Holzapfel, G.A.
    Biomechanics and Modeling in Mechanobiology 15 229-244 (2016)
    The remarkable mechanical properties of cartilage derive from an interplay of isotropically distributed, densely packed and negatively charged proteoglycans; a highly anisotropic and inhomogeneously oriented fiber network of collagens; and an interstitial electrolytic fluid. We propose a new 3D finite strain constitutive model capable of simultaneously addressing both solid (reinforcement) and fluid (permeability) dependence of the tissue’s mechanical response on the patient-specific collagen fiber network. To represent fiber reinforcement, we integrate the strain energies of single collagen fibers—weighted by an orientation distribution function (ODF) defined over a unit sphere—over the distributed fiber orientations in 3D. We define the anisotropic intrinsic permeability of the tissue with a structure tensor based again on the integration of the local ODF over all spatial fiber orientations. By design, our modeling formulation accepts structural data on patient-specific collagen fiber networks as determined via diffusion tensor MRI. We implement our new model in 3D large strain finite elements and study the distributions of interstitial fluid pressure, fluid pressure load support and shear stress within a cartilage sample under indentation. Results show that the fiber network dramatically increases interstitial fluid pressure and focuses it near the surface. Inhomogeneity in the tissue’s composition also increases fluid pressure and reduces shear stress in the solid. Finally, a biphasic neo-Hookean material model, as is available in commercial finite element codes, does not capture important features of the intra-tissue response, e.g., distributions of interstitial fluid pressure and principal shear stress. © 2015, Springer-Verlag Berlin Heidelberg.
    view abstractdoi: 10.1007/s10237-015-0685-x
  • 2016 • 436 Wiring of the aldehyde oxidoreductase PaoABC to electrode surfaces via entrapment in low potential phenothiazine-modified redox polymers
    Pinyou, P. and Ruff, A. and Pöller, S. and Alsaoub, S. and Leimkühler, S. and Wollenberger, U. and Schuhmann, W.
    Bioelectrochemistry 109 24-30 (2016)
    Phenothiazine-modified redox hydrogels were synthesized and used for the wiring of the aldehyde oxidoreductase PaoABC to electrode surfaces. The effects of the pH value and electrode surface modification on the biocatalytic activity of the layers were studied in the presence of vanillin as the substrate. The enzyme electrodes were successfully employed as bioanodes in vanillin/O2 biofuel cells in combination with a high potential bilirubin oxidase biocathode. Open circuit voltages of around 700mV could be obtained in a two compartment biofuel cell setup. Moreover, the use of a rather hydrophobic polymer with a high degree of crosslinking sites ensures the formation of stable polymer/enzyme films which were successfully used as bioanode in membrane-less biofuel cells. © 2015 Elsevier B.V.
    view abstractdoi: 10.1016/j.bioelechem.2015.12.005
  • 2016 • 435 Interaction of C60 fullerene complexed to doxorubicin with model bilipid membranes and its uptake by HeLa cells
    Prylutskyy, Yu. and Bychko, A. and Sokolova, V. and Prylutska, S. and Evstigneev, M. and Rybalchenko, V. and Epple, M. and Scharff, P.
    Materials Science and Engineering C 59 398-403 (2016)
    With an aim to elucidate the effects of C60 fullerene complexed with antibiotic doxorubicin (Dox) on model bilipid membranes (BLM), the investigation of the electrical properties of BLM under the action of Dox and C60 fullerene, and of their complex, C60+ Dox,was performed. The complex aswell as its components exert a clearly detectable influence on BLM, which is concentration-dependent and also depends on phospholipid composition. The mechanism of this effect originates either from intermolecular interaction of the drug with fatty-acid residues of phospholipids, or from membranotropic effects of the drug-induced lipid peroxidation, or from the sum of these two effects. By fluorescence microscopy the entering of C60 + Dox complex into HeLa cells was directly shown. © 2015 Elsevier B.V. All rights reserved.
    view abstractdoi: 10.1016/j.msec.2015.10.049
  • 2016 • 434 A cascade screening approach for the identification of Bcr-Abl myristate pocket binders active against wild type and T315I mutant
    Radi, M. and Schneider, R. and Fallacara, A.L. and Botta, L. and Crespan, E. and Tintori, C. and Maga, G. and Kissova, M. and Calgani, A. and Richters, A. and Musumeci, F. and Rauh, D. and Schenone, S.
    Bioorganic and Medicinal Chemistry Letters 26 3436-3440 (2016)
    The major clinical challenge in drug-resistant chronic myelogenous leukemia (CML) is currently represented by the Bcr-Abl T315I mutant, which is unresponsive to treatment with common first and second generation ATP-competitive tyrosine kinase inhibitors (TKIs). Allosteric inhibition of Bcr-Abl represent a new frontier in the fight against resistant leukemia and few candidates have been identified in the last few years. Among these, myristate pocket (MP) binders discovered by Novartis (e.g. GNF2/5) showed promising results, although they proved to be active against the T315I mutant only in combination with first and second generation ATP-competitive inhibitors. Here we used a cascade screening approach based on sequential fluorescence polarization (FP) screening, in silico docking/dynamics studies and kinetic-enzymatic studies to identify novel MP binders. A pyrazolo[3,4-d]pyrimidine derivative (6) has been identified as a promising allosteric inhibitor active on 32D leukemia cell lines (expressing Bcr-Abl WT and T315I) with no need of combination with any ATP-competitive inhibitor. © 2016 Elsevier Ltd
    view abstractdoi: 10.1016/j.bmcl.2016.06.051
  • 2016 • 433 Benzoic Acid and Chlorobenzoic Acids: Thermodynamic Study of the Pure Compounds and Binary Mixtures with Water
    Reschke, T. and Zherikova, K.V. and Verevkin, S.P. and Held, C.
    Journal of Pharmaceutical Sciences 105 1050-1058 (2016)
    Benzoic acid is a model compound for drug substances in pharmaceutical research. Process design requires information about thermodynamic phase behavior of benzoic acid and its mixtures with water and organic solvents. This work addresses phase equilibria that determine stability and solubility. In this work, Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) was used to model the phase behavior of aqueous and organic solutions containing benzoic acid and chlorobenzoic acids. Absolute vapor pressures of benzoic acid and 2-, 3-, and 4-chlorobenzoic acid from literature and from our own measurements were used to determine pure-component PC-SAFT parameters. Two binary interaction parameters between water and/or benzoic acid were used to model vapor-liquid and liquid-liquid equilibria of water and/or benzoic acid between 280 and 413 K. The PC-SAFT parameters and 1 binary interaction parameter were used to model aqueous solubility of the chlorobenzoic acids. Additionally, solubility of benzoic acid in organic solvents was predicted without using binary parameters. All results showed that pure-component parameters for benzoic acid and for the chlorobenzoic acids allowed for satisfying modeling phase equilibria. The modeling approach established in this work is a further step to screen solubility and to predict the whole phase region of mixtures containing pharmaceuticals. © 2016 American Pharmacists Association®.
    view abstractdoi: 10.1016/j.xphs.2015.12.020
  • 2016 • 432 A redox proteomics approach to investigate the mode of action of nanomaterials
    Riebeling, C. and Wiemann, M. and Schnekenburger, J. and Kuhlbusch, T.A.J. and Wohlleben, W. and Luch, A. and Haase, A.
    Toxicology and Applied Pharmacology 299 24-29 (2016)
    Numbers of engineered nanomaterials (ENMs) are steadily increasing. Therefore, alternative testing approaches with reduced costs and high predictivity suitable for high throughput screening and prioritization are urgently needed to ensure a fast and effective development of safe products. In parallel, extensive research efforts are targeted to understanding modes of action of ENMs, which may also support the development of new predictive assays. Oxidative stress is a widely accepted paradigm associated with different adverse outcomes of ENMs. It has frequently been identified in in vitro and in vivo studies and different assays have been developed for this purpose. Fluorescent dye based read-outs are most frequently used for cell testing in vitro but may be limited due to possible interference of the ENMs. Recently, other assays have been put forward such as acellular determination of ROS production potential using methods like electron spin resonance, antioxidant quantification or the use of specific sensors. In addition, Omics based approaches have gained increasing attention. In particular, redox proteomics can combine the assessment of oxidative stress with the advantage of getting more detailed mechanistic information. Here we propose a comprehensive testing strategy for assessing the oxidative stress potential of ENMs, which combines acellular methods and fast in vitro screening approaches, as well as a more involved detailed redox proteomics approach. This allows for screening and prioritization in a first tier and, if required, also for unraveling mechanistic details down to compromised signaling pathways. © 2016 Published by Elsevier Inc.
    view abstractdoi: 10.1016/j.taap.2016.01.019
  • 2016 • 431 In vivo and in situ synchrotron radiation-based μ-XRF reveals elemental distributions during the early attachment phase of barnacle larvae and juvenile barnacles
    Senkbeil, T. and Mohamed, T. and Simon, R. and Batchelor, D. and Di Fino, A. and Aldred, N. and Clare, A.S. and Rosenhahn, A.
    Analytical and Bioanalytical Chemistry 408 1487-1496 (2016)
    Barnacles are able to establish stable surface contacts and adhere underwater. While the composition of adult barnacle cement has been intensively studied, far less is known about the composition of the cement of the settlement-stage cypris larva. The main challenge in studying the adhesives used by these larvae is the small quantity of material available for analysis, being on the order of nanograms. In this work, we applied, for the first time, synchrotron radiation-based μ-X-ray fluorescence analysis (SR-μ-XRF) for in vivo and in situ analysis of young barnacles and barnacle cyprids. To obtain biologically relevant information relating to the body tissues, adhesives, and shell of the organisms, an in situ sample environment was developed to allow direct microprobe investigation of hydrated specimens without pretreatment of the samples. In 8-day-old juvenile barnacles (Balanus improvisus), the junctions between the six plates forming the shell wall showed elevated concentrations of calcium, potassium, bromine, strontium, and manganese. Confocal measurements allowed elemental characterization of the adhesive interface of recently attached cyprids (Balanus amphitrite), and substantiated the accumulation of bromine both at the point of initial attachment as well as within the cyprid carapace. In situ measurements of the cyprid cement established the presence of bromine, chlorine, iodine, sulfur, copper, iron, zinc, selenium, and nickel for both species. The previously unrecognized presence of bromine, iron, and selenium in the cyprid permanent adhesive will hopefully inspire further biochemical investigations of the function of these substances. © 2015 Springer-Verlag Berlin Heidelberg.
    view abstractdoi: 10.1007/s00216-015-9253-6
  • 2016 • 430 Surface wettability and energy effects on the biological performance of poly-3-hydroxybutyrate films treated with RF plasma
    Syromotina, D.S. and Surmenev, R.A. and Surmeneva, M.A. and Boyandin, A.N. and Nikolaeva, E.D. and Prymak, O. and Epple, M. and Ulbricht, M. and Oehr, C. and Volova, T.G.
    Materials Science and Engineering C 62 450-457 (2016)
    The surface properties of poly-3-hydroxybutyrate (P3HB) membranes were modified using oxygen and an ammonia radio-frequency (RF, 13.56 MHz) plasma. The plasma treatment procedures used in the study only affected the surface properties, including surface topography, without inducing any significant changes in the crystalline structure of the polymer, with the exception being a power level of 250 W. The wettability of the modified P3HB surfaces was significantly increased after the plasma treatment, irrespective of the treatment procedure used. It was revealed that both surface chemistry and surface roughness changes caused by the plasma treatment affected surface wettability. A treatment-induced surface aging effect was observed and resulted in an increase in the water contact angle and a decrease in the surface free energy. However, the difference in the water contact angle between the polymers that had been treated for 4 weeks and the untreated polymer surfaces was still significant. A dependence between cell adhesion and proliferation and the polar component of the surface energy was revealed. The increase in the polar component after the ammonia plasma modification significantly increased cell adhesion and proliferation on biodegradable polymer surfaces compared to the untreated P3HB and the P3HB modified using an oxygen plasma. © 2016 Elsevier B.V.
    view abstractdoi: 10.1016/j.msec.2016.01.075
  • 2016 • 429 Making the hydrogen evolution reaction in polymer electrolyte membrane electrolysers even faster
    Tymoczko, J. and Calle-Vallejo, F. and Schuhmann, W. and Bandarenka, A.S.
    Nature Communications 7 (2016)
    Although the hydrogen evolution reaction (HER) is one of the fastest electrocatalytic reactions, modern polymer electrolyte membrane (PEM) electrolysers require larger platinum loadings (∼0.5-1.0 mg cm-2) than those in PEM fuel cell anodes and cathodes altogether (∼0.5 mg cm-2). Thus, catalyst optimization would help in substantially reducing the costs for hydrogen production using this technology. Here we show that the activity of platinum(111) electrodes towards HER is significantly enhanced with just monolayer amounts of copper. Positioning copper atoms into the subsurface layer of platinum weakens the surface binding of adsorbed H-intermediates and provides a twofold activity increase, surpassing the highest specific HER activities reported for acidic media under similar conditions, to the best of our knowledge. These improvements are rationalized using a simple model based on structure-sensitive hydrogen adsorption at platinum and copper-modified platinum surfaces. This model also solves a long-lasting puzzle in electrocatalysis, namely why polycrystalline platinum electrodes are more active than platinum(111) for the HER.
    view abstractdoi: 10.1038/ncomms10990
  • 2016 • 428 Ions and solvation at biointerfaces
    Valtiner, M. and Erbe, A. and Rosenhahn, A.
    Biointerphases 11 (2016)
    doi: 10.1116/1.4942207
  • 2016 • 427 Antifouling and Antibacterial Multifunctional Polyzwitterion/Enzyme Coating on Silicone Catheter Material Prepared by Electrostatic Layer-by-Layer Assembly
    Vaterrodt, A. and Thallinger, B. and Daumann, K. and Koch, D. and Guebitz, G.M. and Ulbricht, M.
    Langmuir 32 1347-1359 (2016)
    The formation of bacterial biofilms on indwelling medical devices generally causes high risks for adverse complications such as catheter-associated urinary tract infections. In this work, a strategy for synthesizing innovative coatings of poly(dimethylsiloxane) (PDMS) catheter material, using layer-by-layer assembly with three novel functional polymeric building blocks, is reported, i.e., an antifouling copolymer with zwitterionic and quaternary ammonium side groups, a contact biocidal derivative of that polymer with octyl groups, and the antibacterial hydrogen peroxide (H2O2) producing enzyme cellobiose dehydrogenase (CDH). CDH oxidizes oligosaccharides by transferring electrons to oxygen, resulting in the production of H2O2. The design and synthesis of random copolymers which combine segments that have antifouling properties by zwitterionic groups and can be used for electrostatically driven layer-by-layer (LbL) assembly at the same time were based on the atom-transfer radical polymerization of dimethylaminoethyl methacrylate and subsequent partial sulfobetainization with 1,3-propane sultone followed by quaternization with methyl iodide only or octyl bromide and thereafter methyl iodide. The alternating multilayer systems were formed by consecutive adsorption of the novel polycations with up to 50% zwitterionic groups and of poly(styrenesulfonate) as the polyanion. Due to its negative charge, enzyme CDH was also firmly embedded as a polyanionic layer in the multilayer system. This LbL coating procedure was first performed on prefunctionalized silicon wafers and studied in detail with ellipsometry as well as contact angle (CA) and zetapotential (ZP) measurements before it was transferred to prefunctionalized PDMS and analyzed by CA and ZP measurements as well as atomic force microscopy. The coatings comprising six layers were stable and yielded a more neutral and hydrophilic surface than did PDMS, the polycation with 50% zwitterionic groups having the largest effect. Enzyme activity was found to be dependent on the depth of embedment in the multilayer coating. Depending on the used polymeric building block, up to a 60% reduction in the amount of adhering bacteria and clear evidence for killed bacteria due to the antimicrobial functionality of the coating could be confirmed. Overall, this work demonstrates the feasibility of an easy to perform and shape-independent method for preparing an antifouling and antimicrobial coating for the significant reduction of biofilm formation and thus reducing the risk of acquiring infections by using urinary catheters. © 2016 American Chemical Society.
    view abstractdoi: 10.1021/acs.langmuir.5b04303
  • 2016 • 426 Small angle X-ray scattering as a high-throughput method to classify antimicrobial modes of action
    Von Gundlach, A.R. and Garamus, V.M. and Gorniak, T. and Davies, H.A. and Reischl, M. and Mikut, R. and Hilpert, K. and Rosenhahn, A.
    Biochimica et Biophysica Acta - Biomembranes 1858 918-925 (2016)
    Multi-drug resistant bacteria are currently undermining our health care system worldwide. While novel antimicrobial drugs, such as antimicrobial peptides, are urgently needed, identification of new modes of action is money and time consuming, and in addition current approaches are not available in a high throughput manner. Here we explore how small angle X-ray scattering (SAXS) as high throughput method can contribute to classify the mode of action for novel antimicrobials and therefore supports fast decision making in drug development. Using data bases for natural occurring antimicrobial peptides or predicting novel artificial peptides, many candidates can be discovered that will kill a selected target bacterium. However, in order to narrow down the selection it is important to know if these peptides follow all the same mode of action. In addition, the mode of action should be different from conventional antibiotics, in consequence peptide candidates can be developed further into drugs against multi-drug resistant bacteria. Here we used one short antimicrobial peptide with unknown mode of action and compared the ultrastructural changes of Escherichia coli cells after treatment with the peptide to cells treated with classic antibiotics. The key finding is that SAXS as a structure sensitive tool provides a rapid feedback on drug induced ultrastructural alterations in whole E. coli cells. We could demonstrate that ultrastructural changes depend on the used antibiotics and their specific mode of action. This is demonstrated using several well characterized antimicrobial compounds and the analysis of resulting SAXS curves by principal component analysis. To understand the result of the PCA analysis, the data is correlated with TEM images. In contrast to real space imaging techniques, SAXS allows to obtain nanoscale information averaged over approximately one million cells. The measurement takes only seconds, while conventional tests to identify a mode of action require days or weeks per single substance. The antimicrobial peptide showed a different mode of action as all tested antibiotics including polymyxin B and is therefore a good candidate for further drug development. We envision SAXS to become a useful tool within the high-throughput screening pipeline of modern drug discovery. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert. © 2015 Elsevier B.V.
    view abstractdoi: 10.1016/j.bbamem.2015.12.022
  • 2016 • 425 Influence of agglomeration and specific lung lining lipid/protein interaction on short-term inhalation toxicity
    Wohlleben, W. and Driessen, M.D. and Raesch, S. and Schaefer, U.F. and Schulze, C. and Vacano, B.V. and Vennemann, A. and Wiemann, M. and Ruge, C.A. and Platsch, H. and Mues, S. and Ossig, R. and Tomm, J.M. and Schnekenburger, J. ...
    Nanotoxicology 10 970-980 (2016)
    Abstract: Lung lining fluid is the first biological barrier nanoparticles (NPs) encounter during inhalation. As previous inhalation studies revealed considerable differences between surface functionalized NPs with respect to deposition and toxicity, our aim was to investigate the influence of lipid and/or protein binding on these processes. Thus, we analyzed a set of surface functionalized NPs including different SiO2 and ZrO2 in pure phospholipids, CuroSurfTM and purified native porcine pulmonary surfactant (nS). Lipid binding was surprisingly low for pure phospholipids and only few NPs attracted a minimal lipid corona. Additional presence of hydrophobic surfactant protein (SP) B in CuroSurfTM promoted lipid binding to NPs functionalized with Amino or PEG residues. The presence of the hydrophilic SP A in nS facilitated lipid binding to all NPs. In line with this the degree of lipid and protein affinities for different surface functionalized SiO2 NPs in nS followed the same order (SiO2 Phosphate ∼ unmodified SiO2 < SiO2 PEG < SiO2 Amino NPs). Agglomeration and biomolecule interaction of NPs in nS was mainly influenced by surface charge and hydrophobicity. Toxicological differences as observed in short-term inhalation studies (STIS) were mainly influenced by the core composition and/or surface reactivity of NPs. However, agglomeration in lipid media and lipid/protein affinity appeared to play a modulatory role on short-term inhalation toxicity. For instance, lipophilic NPs like ZrO2, which are interacting with nS to a higher extent, exhibited a far higher lung burden than their hydrophilic counterparts, which deserves further attention to predict or model effects of respirable NPs. © 2016 Informa UK Limited, trading as Taylor & Francis Group.
    view abstractdoi: 10.3109/17435390.2016.1155671
  • 2016 • 424 Spearhead Nanometric Field-Effect Transistor Sensors for Single-Cell Analysis
    Zhang, Y. and Clausmeyer, J. and Babakinejad, B. and López Córdoba, A. and Ali, T. and Shevchuk, A. and Takahashi, Y. and Novak, P. and Edwards, C. and Lab, M. and Gopal, S. and Chiappini, C. and Anand, U. and Magnani, L. and Co...
    ACS Nano 10 3214-3221 (2016)
    Nanometric field-effect-transistor (FET) sensors are made on the tip of spear-shaped dual carbon nanoelectrodes derived from carbon deposition inside double-barrel nanopipettes. The easy fabrication route allows deposition of semiconductors or conducting polymers to comprise the transistor channel. A channel from electrodeposited poly pyrrole (PPy) exhibits high sensitivity toward pH changes. This property is exploited by immobilizing hexokinase on PPy nano-FETs to give rise to a selective ATP biosensor. Extracellular pH and ATP gradients are key biochemical constituents in the microenvironment of living cells; we monitor their real-time changes in relation to cancer cells and cardiomyocytes. The highly localized detection is possible because of the high aspect ratio and the spear-like design of the nano-FET probes. The accurately positioned nano-FET sensors can detect concentration gradients in three-dimensional space, identify biochemical properties of a single living cell, and after cell membrane penetration perform intracellular measurements. © 2016 American Chemical Society.
    view abstractdoi: 10.1021/acsnano.5b05211
  • 2015 • 423 Combinatorial Development of Fe-Co-Nb Thin Film Magnetic Nanocomposites
    Alexandrakis, V. and Wallisch, W. and Hamann, S. and Varvaro, G. and Fidler, J. and Ludwig, Al.
    ACS Combinatorial Science 17 698-703 (2015)
    A Fe-Co-Nb thin film materials library was deposited by combinatorial magnetron sputtering and investigated by high-throughput methods to identify new noncubic ferromagnetic phases, indicating that combinatorial experimentation is an efficient method to discover new ferromagnetic phases adequate for permanent magnet applications. Structural analysis indicated the formation of a new magnetic ternary compound (Fe,Co)3Nb with a hexagonal crystal structure (C36) embedded in an FeCo-based matrix. This nanocomposite exhibits characteristics of a two-phase ferromagnetic system, the so-called hard-soft nanocomposites, indicating that the new phase (Fe,Co)3Nb is ferromagnetic. Magnetic hysteresis loops at various angles revealed that the magnetization reversal process is governed by a domain wall pinning mechanism. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/acscombsci.5b00116
  • 2015 • 422 Bioconjugated gold nanoparticles penetrate into spermatozoa depending on plasma membrane status
    Barchanski, A. and Taylor, U. and Sajti, C.L. and Gamrad, L. and Kues, W.A. and Rath, D. and Barcikowski, S.
    Journal of Biomedical Nanotechnology 11 1597-1607 (2015)
    Spermatozoa are not only essential for animal reproduction they also represent important tools for the manipulation of animal genetics. For instance, the genetic labeling and analysis of spermatozoa could provide a prospective complementation of pre-fertilization diagnosis and could help to prevent the inheritance of defective alleles during artificial insemination or to select beneficial traits in livestock. Spermatozoa feature extremely specialized membrane organization and restricted transport mechanisms making the labeling of genetically interesting DNA-sequences, e.g., with gold nanoparticles, a particular challenge. Here, we present a systematic study on the size-related internalization of ligand-free, monovalent and bivalent polydisperse gold nanoparticles, depending on spermatozoa membrane status. While monovalent conjugates were coupled solely to either negatively-charged oligonucleotides or positively-charged cell-penetrating peptides, bivalent conjugates were functionalized with both molecules simultaneously. The results clearly indicate that the cell membrane of acrosome-intact, bovine spermatozoa was neither permeable to ligand-free or oligonucleotide-conjugated nanoparticles, nor responsive to the mechanisms of cell-penetrating peptides. Interestingly, after acrosome reaction, which comprises major changes in sperm membrane composition, fluidity and charge, high numbers of monovalent and bivalent nanoparticles were found in the postequatorial segment, depicting a close and complex correlation between particle internalization and membrane organization. Additionally, depending on the applied peptide and for nanoparticle sizes <10 nm even a successive nuclear penetration was observed, making the bivalent conjugates promising for future genetic delivery and sorting issues. Copyright © 2015 American Scientific Publishers All rights reserved.
    view abstractdoi: 10.1166/jbn.2015.2094
  • 2015 • 421 Structure-based design and synthesis of covalent-reversible inhibitors to overcome drug resistance in EGFR
    Basu, D. and Richters, A. and Rauh, D.
    Bioorganic and Medicinal Chemistry 23 2767-2780 (2015)
    The clinical success of covalent kinase inhibitors in the treatment of EGFR-dependent non-small cell lung cancer (NSCLC) has rejuvenated the appreciation of reactive small molecules. Acquired drug resistance against first-line EGFR inhibitors remains the major bottleneck in NSCLC and is currently addressed by the application of fine-tuned covalent drugs. Here we report the design, synthesis and biochemical evaluation of a novel class of EGFR inhibitors with a covalent yet reversible warhead. A series of WZ4002 analogs, derived from anilinopyrimidine and 3-substituted-2-cyanoacrylamide scaffolds, exhibit strong and selective inhibitory activity against clinically relevant EGFRL858R and EGFRL858R/T790M. © 2015 Elsevier Ltd. All rights reserved.
    view abstractdoi: 10.1016/j.bmc.2015.04.038
  • 2015 • 420 Molecular motions in supercooled and glassy ibuprofen: Deuteron magnetic resonance and high-resolution rheology study
    Bauer, S. and Storek, M. and Gainaru, C. and Zimmermann, H.b and Böhmer, R.
    Journal of Physical Chemistry B 119 5087-5095 (2015)
    Using deuteron nuclear magnetic resonance, the molecular motions of specifically isotope-labeled ibuprofen were probed at the carboxylic group and at the methin group next to it. Spin relaxometry revealed slight differences between the molecular motions of the two isotopomers that are rationalized with reference to the hydrogen bonding of the COOH moiety. In the glassy state, a small-angle jump process among about four sites, related to the so-called γ-process, was identified using stimulated-echo spectroscopy. Indications for a Debye-like process, previously found to leave a weak signature in the dielectric loss, could not unambiguously be detected in magnetic resonance or shear mechanical experiments carried out for supercooled liquid ibuprofen. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/acs.jpcb.5b01072
  • 2015 • 419 Wet-chemical synthesis of different bismuth telluride nanoparticles using metal organic precursors-single source vs. dual source approach
    Bendt, G. and Weber, A. and Heimann, S. and Assenmacher, W. and Prymak, O. and Schulz, S.
    Dalton Transactions 44 14272-14280 (2015)
    Thermolysis of the single source precursor (Et<inf>2</inf>Bi)<inf>2</inf>Te 1 in DIPB at 80 °C yielded phase-pure Bi<inf>4</inf>Te<inf>3</inf> nanoparticles, while mixtures of Bi<inf>4</inf>Te<inf>3</inf> and elemental Bi were formed at higher temperatures. In contrast, cubic Bi<inf>2</inf>Te particles were obtained by thermal decomposition of Et<inf>2</inf>BiTeEt 2 in DIPB. Moreover, a dual source approach (hot injection method) using the reaction of Te(SiEt<inf>3</inf>)<inf>2</inf> and Bi(NMe<inf>2</inf>)<inf>3</inf> was applied for the synthesis of different pure Bi-Te phases including Bi<inf>2</inf>Te, Bi<inf>4</inf>Te<inf>3</inf> and Bi<inf>2</inf>Te<inf>3</inf>, which were characterized by PXRD, REM, TEM and EDX. The influence of reaction temperature, precursor molar ratio and thermolysis conditions on the resulting material phase was verified. Moreover, reactions of alternate bismuth precursors such as Bi(NEt<inf>2</inf>)<inf>3</inf>, Bi(NMeEt)<inf>3</inf> and BiCl<inf>3</inf> with Te(SiEt<inf>3</inf>)<inf>2</inf> were investigated. © 2015 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c5dt02072g
  • 2015 • 418 Process boundaries of irreversible scCO2-assisted phase separation in biphasic whole-cell biocatalysis
    Brandenbusch, C. and Glonke, S. and Collins, J. and Hoffrogge, R. and Grunwald, K. and Bühler, B. and Schmid, A. and Sadowski, G.
    Biotechnology and Bioengineering 112 2316-2323 (2015)
    The formation of stable emulsions in biphasic biotransformations catalyzed by microbial cells turned out to be a major hurdle for industrial implementation. Recently, a cost-effective and efficient downstream processing approach, using supercritical carbon dioxide (scCO2) for both irreversible emulsion destabilization (enabling complete phase separation within minutes of emulsion treatment) and product purification via extraction has been proposed by Brandenbusch et al. (2010). One of the key factors for a further development and scale-up of the approach is the understanding of the mechanism underlying scCO2-assisted phase separation. A systematic approach was applied within this work to investigate the various factors influencing phase separation during scCO2 treatment (that is pressure, exposure of the cells to CO2, and changes of cell surface properties). It was shown that cell toxification and cell disrupture are not responsible for emulsion destabilization. Proteins from the aqueous phase partially adsorb to cells present at the aqueous-organic interface, causing hydrophobic cell surface characteristics, and thus contribute to emulsion stabilization. By investigating the change in cell-surface hydrophobicity of these cells during CO2 treatment, it was found that a combination of catastrophic phase inversion and desorption of proteins from the cell surface is responsible for irreversible scCO2 mediated phase separation. These findings are essential for the definition of process windows for scCO2-assisted phase separation in biphasic whole-cell biocatalysis. © 2015 Wiley Periodicals, Inc.
    view abstractdoi: 10.1002/bit.25655
  • 2015 • 417 Extracellular Matrix Glycoprotein-Derived Synthetic Peptides Differentially Modulate Glioma and Sarcoma Cell Migration
    Brösicke, N. and Sallouh, M. and Prior, L.-M. and Job, A. and Weberskirch, R. and Faissner, A.
    Cellular and Molecular Neurobiology 35 741-753 (2015)
    Glycoproteins of the extracellular matrix (ECM) regulate proliferation, migration, and differentiation in numerous cell lineages. ECM functions are initiated by small peptide sequences embedded in large constituents that are recognized by specific cellular receptors. In this study, we have investigated the biological effects of peptides derived from collagen type IV and tenascin-C compared to the well-known RGD peptide originally discovered in fibronectin. The influence of glycoproteins and corresponding peptides on the migration of the glioma cell lines U-251-MG and U-373-MG and the sarcoma line S-117 was studied. When the cell lines were tested in a modified Boyden chamber assay on filters coated with the ECM glycoproteins, glioma cells showed a strong migration response on tenascin-C and the basal lamina constituent collagen IV, in contrast to S-117 cells. In order to identify relevant stimulatory motifs, peptides derived from fibronectin (6NHX-GRGDSF), tenascin-C (TN-C, VSWRAPTA), and collagen type IV (MNYYSNS) were compared, either applied in solution in combination with ECM glycoprotein substrates, in solution in the presence of untreated membranes, or coated on the filters of the Boyden chambers. Using this strategy, we could identify the novel tenascin-C-derived peptide motif VSWRAPTA as a migration stimulus for glioma cells. Furthermore, while kin peptides generally blocked the effects of the respective homologous ECM proteins, unexpected effects were observed in heterologous situations. There, in several cases, addition of soluble peptides strongly boosted the response to the coated ECM proteins. We propose that peptides may synergize or antagonize each other by stimulating different signaling pathways. © 2015, Springer Science+Business Media New York.
    view abstractdoi: 10.1007/s10571-015-0170-1
  • 2015 • 416 Shear-Induced Detachment of Polystyrene Beads from SAM-Coated Surfaces
    Cho, K.L. and Rosenhahn, A. and Thelen, R. and Grunze, M. and Lobban, M. and Karahka, M.L. and Kreuzer, H.J.
    Langmuir 31 11105-11112 (2015)
    In this work we experimentally and theoretically analyze the detachment of microscopic polystyrene beads from different self-assembled monolayer (SAM) surfaces in a shear flow in order to develop a mechanistic model for the removal of cells from surfaces. The detachment of the beads from the surface is treated as a thermally activated process applying an Arrhenius Ansatz to determine the activation barrier and attempt frequency of the rate determing step in bead removal. The statistical analysis of the experimental shear detachment data obtained in phosphate-buffered saline buffer results in an activation energy around 20 kJ/mol, which is orders of magnitude lower than the adhesion energy measured by atomic force microscopy (AFM). The same order of magnitude for the adhesion energy measured by AFM is derived from ab initio calculations of the van der Waals interaction energy between the polystyrene beads and the SAM-covered gold surface. We conclude that the rate determing step for detachment of the beads is the initiation of rolling on the surface (overcoming static friction) and not physical detachment, i.e., lifting the particle off the surface. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/acs.langmuir.5b02321
  • 2015 • 415 The dynamic influence of cells on the formation of stable emulsions in organic–aqueous biotransformations
    Collins, J. and Grund, M. and Brandenbusch, C. and Sadowski, G. and Schmid, A. and Bühler, B.
    Journal of Industrial Microbiology and Biotechnology 42 1011-1026 (2015)
    Emulsion stability plays a crucial role for mass transfer and downstream processing in organic–aqueous bioprocesses based on whole microbial cells. In this study, emulsion stability dynamics and the factors determining them during two-liquid phase biotransformation were investigated for stereoselective styrene epoxidation catalyzed by recombinant Escherichia coli. Upon organic phase addition, emulsion stability rapidly increased correlating with a loss of solubilized protein from the aqueous cultivation broth and the emergence of a hydrophobic cell fraction associated with the organic–aqueous interface. A novel phase inversion-based method was developed to isolate and analyze cellular material from the interface. In cell-free experiments, a similar loss of aqueous protein did not correlate with high emulsion stability, indicating that the observed particle-based emulsions arise from a convergence of factors related to cell density, protein adsorption, and bioreactor conditions. During styrene epoxidation, emulsion destabilization occurred correlating with product-induced cell toxification. For biphasic whole-cell biotransformations, this study indicates that control of aqueous protein concentrations and selective toxification of cells enables emulsion destabilization and emphasizes that biological factors and related dynamics must be considered in the design and modeling of respective upstream and especially downstream processes. © 2015, Society for Industrial Microbiology and Biotechnology.
    view abstractdoi: 10.1007/s10295-015-1621-x
  • 2015 • 414 Reactions of Superoxide with Iron Porphyrins in the Bulk and the Near-Surface Region of Ionic Liquids
    Dees, A. and Jux, N. and Tröppner, O. and Dürr, K. and Lippert, R. and Schmid, M. and Küstner, B. and Schlücker, S. and Steinrück, H.-P. and Gottfried, J.M. and Ivanović-Burmazović, I.
    Inorganic Chemistry 54 6862-6872 (2015)
    The redox reaction of superoxide (KO<inf>2</inf>) with highly charged iron porphyrins (Fe(P4+), Fe(P8+), and Fe(P8-)) has been investigated in the ionic liquids (IL) [EMIM][Tf<inf>2</inf>N] (1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) and [EMIM][B(CN)<inf>4</inf>] (1-ethyl-3-methylimidazolium tetracyanoborate) by using time-resolved UV/vis stopped-flow, electrochemistry, cryospray mass spectrometry, EPR, and XPS measurements. Stable KO<inf>2</inf> solutions in [EMIM][Tf<inf>2</inf>N] can be prepared up to a 15 mM concentration and are characterized by a signal in EPR spectrum at g = 2.0039 and by the 1215 cm-1 stretching vibration in the resonance Raman spectrum. While the negatively charged iron porphyrin Fe(P8-) does not react with superoxide in IL, Fe(P4+) and Fe(P8+) do react in a two-step process (first a reduction of the Fe(III) to the Fe(II) form, followed by the binding of superoxide to Fe(II)). In the reaction with KO<inf>2</inf>, Fe(P4+) and Fe(P8+) show similar rate constants (e.g., in the case of Fe(P4+): k<inf>1</inf> = 18.6 ± 0.5 M-1 s-1 for the first reaction step, and k<inf>2</inf> = 2.8 ± 0.1 M-1 s-1 for the second reaction step). Notably, these rate constants are four to five orders of magnitude lower in [EMIM][Tf<inf>2</inf>N] than in conventional solvents such as DMSO. The influence of the ionic liquid is also apparent during electrochemical experiments, where the redox potentials for the corresponding Fe(III)/Fe(II) couples are much more negative in [EMIM][Tf<inf>2</inf>N] than in DMSO. This modified redox and kinetic behavior of the positively charged iron porphyrins results from their interactions with the anions of the ionic liquid, while the nucleophilicity of the superoxide is reduced by its interactions with the cations of the ionic liquid. A negligible vapor pressure of [EMIM][B(CN)<inf>4</inf>] and a sufficient enrichment of Fe(P8+) in a close proximity to the surface enabled XPS measurements as a case study for monitoring direct changes in the electronic structure of the metal centers during redox processes in solution and at liquid/solid interfaces. (Figure Presented). © 2015 American Chemical Society.
    view abstractdoi: 10.1021/acs.inorgchem.5b00770
  • 2015 • 413 Magneto-responsive alginate capsules
    Degen, P. and Zwar, E. and Schulz, I. and Rehage, H.
    Journal of Physics Condensed Matter 27 (2015)
    Upon incorporation of magnetic nanoparticles (mNPs) into gels, composite materials called ferrogels are obtained. These magneto-responsive systems have a wide range of potential applications including switches and sensors as well as drug delivery systems. In this article, we focus on the properties of calcium alginate capsules, which are widely used as carrier systems in medicine and technology. We studied the incorporation of different kinds of mNPs in matrix capsules and in the core and the shell of hollow particles. We found out that not all particle-alginate or particle-CaCl<inf>2</inf> solution combinations were suitable for a successful capsule preparation on grounds of a destabilization of the nanoparticles or the polymer. For those systems allowing the preparation of switchable beads or capsules, we systematically studied the size and microscopic structure of the capsules, their magnetic behavior and mechanical resistance. © 2015 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0953-8984/27/19/194105
  • 2015 • 412 Three-dimensional Cu foam-supported single crystalline mesoporous Cu2O nanothorn arrays for ultra-highly sensitive and efficient nonenzymatic detection of glucose
    Dong, C. and Zhong, H. and Kou, T. and Frenzel, J. and Eggeler, G. and Zhang, Z.
    ACS Applied Materials and Interfaces 7 20215-20223 (2015)
    Highly sensitive and efficient biosensors play a crucial role in clinical, environmental, industrial, and agricultural applications, and tremendous efforts have been dedicated to advanced electrode materials with superior electrochemical activities and low cost. Here, we report a three-dimensional binder-free Cu foam-supported Cu<inf>2</inf>O nanothorn array electrode developed via facile electrochemistry. The nanothorns growing in situ along the specific direction of <011> have single crystalline features and a mesoporous surface. When being used as a potential biosensor for nonenzyme glucose detection, the hybrid electrode exhibits multistage linear detection ranges with ultrahigh sensitivities (maximum of 97.9 mA mM-1 cm-2) and an ultralow detection limit of 5 nM. Furthermore, the electrode presents outstanding selectivity and stability toward glucose detection. The distinguished performances endow this novel electrode with powerful reliability for analyzing human serum samples. These unprecedented sensing characteristics could be ascribed to the synergistic action of superior electrochemical catalytic activity of nanothorn arrays with dramatically enhanced surface area and intimate contact between the active material (Cu<inf>2</inf>O) and current collector (Cu foam), concurrently supplying good conductivity for electron/ion transport during glucose biosensing. Significantly, our findings could guide the fabrication of new metal oxide nanostructures with well-organized morphologies and unique properties as well as low materials cost. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/acsami.5b05738
  • 2015 • 411 Benchmark Thermochemistry for Biologically Relevant Adenine and Cytosine. A Combined Experimental and Theoretical Study
    Emel'yanenko, V.N. and Zaitsau, D.H. and Shoifet, E. and Meurer, F. and Verevkin, S.P. and Schick, C. and Held, C.
    Journal of Physical Chemistry A 119 9680-9691 (2015)
    The thermochemical properties available in the literature for adenine and cytosine are in disarray. A new condensed phase standard (p° = 0.1 MPa) molar enthalpy of formation at T = 298.15 K was measured by using combustion calorimetry. New molar enthalpies of sublimation were derived from the temperature dependence of vapor pressure measured by transpiration and by the quarz-crystal microbalance technique. The heat capacities of crystalline adenine and cytosine were measured by temperature-modulated DSC. Thermodynamic data on adenine and cytosine available in the literature were collected, evaluated, and combined with our experimental results. Thus, the evaluated collection of data together with the new experimental results reported here has helped to resolve contradictions in the available enthalpies of formation. A set of reliable thermochemical data is recommended for adenine and cytosine for further thermochemical calculations. Quantum-chemical calculations of the gas phase molar enthalpies of formation of adenine and cytosine have been performed by using the G4 method and results were in excellent agreement with the recommended experimental data. The standard molar entropies of formation and the standard molar Gibbs functions of formation in crystal and gas state have been calculated. Experimental vapor-pressure data measured in this work were used to estimate pure-component PC-SAFT parameters. This allowed modeling solubility of adenine and cytosine in water over the temperature interval 278-310 K. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/acs.jpca.5b04753
  • 2015 • 410 Targeting Drug Resistance in EGFR with Covalent Inhibitors: A Structure-Based Design Approach
    Engel, J. and Richters, A. and Getlik, M. and Tomassi, S. and Keul, M. and Termathe, M. and Lategahn, J. and Becker, C. and Mayer-Wrangowski, S. and Grütter, C. and Uhlenbrock, N. and Krüll, J. and Schaumann, N. and Eppmann, S. ...
    Journal of Medicinal Chemistry 58 6844-6863 (2015)
    Receptor tyrosine kinases represent one of the prime targets in cancer therapy, as the dysregulation of these elementary transducers of extracellular signals, like the epidermal growth factor receptor (EGFR), contributes to the onset of cancer, such as non-small cell lung cancer (NSCLC). Strong efforts were directed to the development of irreversible inhibitors and led to compound CO-1686, which takes advantage of increased residence time at EGFR by alkylating Cys797 and thereby preventing toxic effects. Here, we present a structure-based approach, rationalized by subsequent computational analysis of conformational ligand ensembles in solution, to design novel and irreversible EGFR inhibitors based on a screening hit that was identified in a phenotype screen of 80 NSCLC cell lines against approximately 1500 compounds. Using protein X-ray crystallography, we deciphered the binding mode in engineered cSrc (T338M/S345C), a validated model system for EGFR-T790M, which constituted the basis for further rational design approaches. Chemical synthesis led to further compound collections that revealed increased biochemical potency and, in part, selectivity toward mutated (L858R and L858R/T790M) vs nonmutated EGFR. Further cell-based and kinetic studies were performed to substantiate our initial findings. Utilizing proteolytic digestion and nano-LC-MS/MS analysis, we confirmed the alkylation of Cys797. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/acs.jmedchem.5b01082
  • 2015 • 409 Discovery of inter-domain stabilizers-a novel assay system for allosteric Akt inhibitors
    Fang, Z. and Simard, J.R. and Plenker, D. and Nguyen, H.D. and Phan, T. and Wolle, P. and Baumeister, S. and Rauh, D.
    ACS Chemical Biology 10 279-288 (2015)
    In addition to the catalytically active kinase domain, most kinases feature regulatory domains that govern their activity. Modulating and interfering with these interdomain interactions presents a major opportunity for understanding biological systems and developing novel therapeutics. Therefore, small molecule inhibitors that target these interactions through an allosteric mode of action have high intrinsic selectivity, as these interactions are often unique to a single kinase or kinase family. Here we report the development of iFLiK (interface-Fluorescent Labels in Kinases), a fluorescence-based assay that can monitor such interdomain interactions. Using iFLiK, we have demonstrated selective detection of allosteric Akt inhibitors that induce an inactive closed conformation unique to Akt. This methodology easily distinguished small molecule allosteric inhibitors from classic ATP-competitive inhibitors. Screening an in-house compound library with iFLiK, we were able to identify novel compounds with a scaffold that has not been previously described for allosteric Akt inhibitors. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/cb500355c
  • 2015 • 408 Mechanism of protection of catalysts supported in redox hydrogel films
    Fourmond, V. and Stapf, S. and Li, H. and Buesen, D. and Birrell, J. and Rüdiger, O. and Lubitz, W. and Schuhmann, W. and Plumeré, N. and Léger, C.
    Journal of the American Chemical Society 137 5494-5505 (2015)
    The use of synthetic inorganic complexes as supported catalysts is a key route in energy production and in industrial synthesis. However, their intrinsic oxygen sensitivity is sometimes an issue. Some of us have recently demonstrated that hydrogenases, the fragile but very efficient biological catalysts of H<inf>2</inf> oxidation, can be protected from O<inf>2</inf> damage upon integration into a film of a specifically designed redox polymer. Catalytic oxidation of H<inf>2</inf> produces electrons which reduce oxygen near the film/solution interface, thus providing a self-activated protection from oxygen [Plumeré et al., Nat Chem. 2014, 6, 822-827]. Here, we rationalize this protection mechanism by examining the time-dependent distribution of species in the hydrogenase/polymer film, using measured or estimated values of all relevant parameters and the numerical and analytical solutions of a realistic reaction-diffusion scheme. Our investigation sets the stage for optimizing the design of hydrogenase-polymer films, and for expanding this strategy to other fragile catalysts. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/jacs.5b01194
  • 2015 • 407 Splenic red pulp macrophages are intrinsically superparamagnetic and contaminate magnetic cell isolates
    Franken, L. and Klein, M. and Spasova, M. and Elsukova, A. and Wiedwald, U. and Welz, M. and Knolle, P. and Farle, M. and Limmer, A. and Kurts, C.
    Scientific Reports 5 (2015)
    A main function of splenic red pulp macrophages is the degradation of damaged or aged erythrocytes. Here we show that these macrophages accumulate ferrimagnetic iron oxides that render them intrinsically superparamagnetic. Consequently, these cells routinely contaminate splenic cell isolates obtained with the use of MCS, a technique that has been widely used in immunological research for decades. These contaminations can profoundly alter experimental results. In mice deficient for the transcription factor SpiC, which lack red pulp macrophages, liver Kupffer cells take over the task of erythrocyte degradation and become superparamagnetic. We describe a simple additional magnetic separation step that avoids this problem and substantially improves purity of magnetic cell isolates from the spleen.
    view abstractdoi: 10.1038/srep12940
  • 2015 • 406 Salt induced reduction of lysozyme adsorption at charged interfaces
    Göhring, H. and Paulus, M. and Salmen, P. and Wirkert, F. and Kruse, T. and Degen, P. and Stuhr, S. and Rehage, H. and Tolan, M.
    Journal of Physics Condensed Matter 27 (2015)
    A study of lysozyme adsorption below a behenic acid membrane and at the solid-liquid interface between aqueous lysozyme solution and a silicon wafer in the presence of sodium chloride is presented. The salt concentration was varied between 1 mmol L-1 and 1000 mmol L-1. X-ray reflectivity data show a clear dependence of the protein adsorption on the salt concentration. Increasing salt concentrations result in a decreased protein adsorption at the interface until a complete suppression at high concentrations is reached. This effect can be attributed to a reduced attractive electrostatic interaction between the positively charged proteins and negatively charged surfaces by charge screening. The measurements at the solid-liquid interfaces show a transition from unoriented order of lysozyme in the adsorbed film to an oriented order with the short protein axis perpendicular to the solid-liquid interface with rising salt concentration. © 2015 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0953-8984/27/23/235103
  • 2015 • 405 Synthesis and post-synthetic modification of amine-, alkyne-, azide- and nitro-functionalized metal-organic frameworks based on DUT-5
    Gotthardt, M.A. and Grosjean, S. and Brunner, T.S. and Kotzel, J. and Gänzler, A.M. and Wolf, S. and Bräse, S. and Kleist, W.
    Dalton Transactions 44 16802-16809 (2015)
    Functionalized 4,4′-biphenyldicarboxylic acid molecules with additional amine, alkyne, azide or nitro groups were prepared and applied in the synthesis of novel metal-organic frameworks and mixed-linker metal-organic frameworks isoreticular to DUT-5. The properties of the frameworks could be tuned by varying the number of functional groups in the materials and the amine groups were employed in post-synthetic modification reactions without changing the framework structure or significantly decreasing the porosity of the materials. © The Royal Society of Chemistry 2015.
    view abstractdoi: 10.1039/c5dt02276b
  • 2015 • 404 A sterically stabilized FeI-FeI semi-rotated conformation of [FeFe] hydrogenase subsite model
    Goy, R. and Bertini, L. and Elleouet, C. and Görls, H. and Zampella, G. and Talarmin, J. and De Gioia, L. and Schollhammer, P. and Apfel, U.-P. and Weigand, W.
    Dalton Transactions 44 1690-1699 (2015)
    The [FeFe] hydrogenase is a highly sophisticated enzyme for the synthesis of hydrogen via a biological route. The rotated state of the H-cluster in the [FeIFeI] form was found to be an indispensable criteria for an effective catalysis. Mimicking the specific rotated geometry of the [FeFe] hydrogenase active site is highly challenging as no protein stabilization is present in model compounds. In order to simulate the sterically demanding environment of the nature's active site, the sterically crowded meso-bis(benzylthio)diphenylsilane (2) was utilized as dithiolate linker in an [2Fe2S] model complex. The reaction of the obtained hexacarbonyl complex 3 with 1,2-bis(dimethylphosphino)ethane (dmpe) results three different products depending on the amount of dmpe used in this reaction: [{Fe2(CO)5{μ-(SCHPh)2SiPh2}}2(μ-dmpe)] (4), [Fe2(CO)5(κ2-dmpe){μ-(SCHPh)2SiPh2}] (5) and [Fe2(CO)5(μ-dmpe){μ-(SCHPh)2SiPh2}] (6). Interestingly, the molecular structure of compound 5 shows a [FeFe] subsite comprising a semi-rotated conformation, which was fully characterized as well as the other isomers 4 and 6 by elemental analysis, IR and NMR spectroscopy, X-ray diffraction analysis (XRD) and DFT calculations. The herein reported model complex is the first example so far reported for [FeIFeI] hydrogenase model complex showing a semi-rotated geometry without the need of stabilization via agostic interactions (Fe⋯H-C). This journal is © The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c4dt03223c
  • 2015 • 403 Calcium phosphate nanoparticles carrying BMP-7 plasmid DNA induce an osteogenic response in MC3T3-E1 pre-osteoblasts
    Hadjicharalambous, C. and Kozlova, D. and Sokolova, V. and Epple, M. and Chatzinikolaidou, M.
    Journal of Biomedical Materials Research - Part A 103 3834-3842 (2015)
    Functionalized calcium phosphate nanoparticles with osteogenic activity were prepared. Polyethyleneimine-stabilized calcium phosphate nanoparticles were coated with a shell of silica and covalently functionalized by silanization with thiol groups. Between the calcium phosphate surface and the outer silica shell, plasmid DNA which encoded either for bone morphogenetic protein 7 (BMP-7) or for enhanced green fluorescent protein was incorporated as cargo. The plasmid DNA-loaded calcium phosphate nanoparticles were used for the transfection of the pre-osteoblastic MC3T3-E1 cells. The cationic nanoparticles showed high transfection efficiency together with a low cytotoxicity. Their potential to induce an osteogenic response by transfection was demonstrated by measuring the alkaline phosphatase (ALP) activity and calcium deposition with alizarin red staining. The expression of the osteogenic markers Alp, Runx2, ColIa1 and Bsp was investigated by means of real-time quantitative polymerase chain reaction. It was shown that phBMP-7-loaded nanoparticles can provide a means of transient transfection and localized production of BMP-7 in MC3T3-E1 cells, with a subsequent increase of two osteogenic markers, specifically ALP activity and calcium accumulation in the extracellular matrix. Future strategies to stimulate bone regeneration focus into enhancing transfection efficiency and achieving higher levels of BMP-7 produced by the transfected cells. © 2015 Wiley Periodicals, Inc.
    view abstractdoi: 10.1002/jbm.a.35527
  • 2015 • 402 Oxidative potential of particulate matter at a German motorway
    Hellack, B. and Quass, U. and Nickel, C. and Wick, G. and Schins, R.P.F. and Kuhlbusch, T.A.J.
    Environmental Sciences: Processes and Impacts 17 868-875 (2015)
    Ambient particulate matter (PM10) was sampled alongside a motorway in North-Rhine Westphalia, Germany, during a one-year period. In sum, 120 PM10 samples on quartz fibre filters, 60 samples at each side of the motorway, were taken during clear cross-wind direction situations, i.e. upwind (local background situation) and downwind (traffic influenced). To quantify the traffic-related oxidative potential (OP), or more precisely the hydroxyl radical (OH) generation potency, these samples were analysed to study their hydrogen peroxide dependent oxidant generation by Electron Paramagnetic Resonance (EPR) spectroscopy using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide. In addition the PM10 mass, the chemical composition and the NO<inf>x</inf> concentrations were determined. For PM10 mass and traffic tracers like Sb, Ba, elemental and organic carbon as well as for NO<inf>x</inf>, an additional contribution to the background concentration caused by the traffic was observed (factor: 1.3-6.0). The downwind measurements showed in 72% of cases higher OH generation potencies with an average factor of 1.4. Significant correlations to OH were detected for Fe (r > 0.58) and Cu (r > 0.57) for the upwind and overall (upwind + downwind, r > 0.44) dataset. At the downwind side these correlations were absent and are assumed to be covered by the interferences with additional soot particles leading to a quenching of OH. Accordingly, no significant overall correlation of the OH generation potency with the traffic intensity was detected. The suggested quenching effect was confirmed via standard diesel soot (SRM 2975) measurements using the EPR approach. In summary, the traffic related PM causes an intrinsic OH generation via Fenton-like reaction but obviously also leads to interferences and scavenging by traffic related carbonaceous compounds. In consequence, for future studies that would link the intrinsic OP and adverse health effects we suggest to analyse the relationship to EC/OC and to use in parallel also a further OP detection method. © 2015 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c4em00605d
  • 2015 • 401 Hybridization of an Aβ-specific antibody fragment with aminopyrazole-based β-sheet ligands displays striking enhancement of target affinity
    Hellmert, M. and Müller-Schiffmann, A. and Peters, M.S. and Korth, C. and Schrader, T.
    Organic and Biomolecular Chemistry 13 2974-2979 (2015)
    Determining Aβ levels in body fluids remains a powerful tool in the diagnostics of Alzheimer's disease. This report delineates a new supramolecular strategy which increases the affinity of antibodies towards Aβ to make diagnostic procedures more sensitive. A monoclonal antibody IC16 was generated to an N-terminal epitope of Aβ and the variable regions of the heavy and light chains were cloned as a recombinant protein (scFv). A 6 × histidine tag was fused to the C-terminus of IC16-scFv allowing hybridization with a small organic β-sheet binder via Ni-NTA complexation. On the other hand, a multivalent nitrilotriacetic acid (NTA)-equipped trimeric aminopyrazole (AP) derivative was synthesized based on a cyclam platform; and experimental evidence was obtained for efficient Ni2+-mediated complex formation with the histidine-tagged antibody species. In a proof of principle experiment the hybrid molecule showed a strong increase in affinity towards Aβ. Thus, the specific binding power of recombinant antibody fragments to their β-sheet rich targets can be conveniently enhanced by non-covalent hybridization with small organic β-sheet binders. © 2015 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c4ob02411g
  • 2015 • 400 The Lys-Specific Molecular Tweezer, CLR01, Modulates Aggregation of the Mutant p53 DNA Binding Domain and Inhibits Its Toxicity
    Herzog, G. and Shmueli, M.D. and Levy, L. and Engel, L. and Gazit, E. and Klärner, F.-G. and Schrader, T. and Bitan, G. and Segal, D.
    Biochemistry 54 3729-3738 (2015)
    The tumor suppressor p53 plays a unique role as a central hub of numerous cell proliferation and apoptotic pathways, and its malfunction due to mutations is a major cause of various malignancies. Therefore, it serves as an attractive target for developing novel anticancer therapeutics. Because of its intrinsically unstable DNA binding domain, p53 unfolds rapidly at physiological temperature. Certain mutants shift the equilibrium toward the unfolded state and yield high-molecular weight, nonfunctional, and cytotoxic β-sheet-rich aggregates that share tinctorial and conformational similarities with amyloid deposits found in various protein misfolding diseases. Here, we examined the effect of a novel protein assembly modulator, the lysine (Lys)-specific molecular tweezer, CLR01, on different aggregation stages of misfolded mutant p53 in vitro and on the cytotoxicity of the resulting p53 aggregates in cell culture. We found that CLR01 induced rapid formation of β-sheet-rich, intermediate-size p53 aggregates yet inhibited further p53 aggregation and reduced the cytotoxicity of the resulting aggregates. Our data suggest that aggregation modulators, such as CLR01, could prevent the formation of toxic p53 aggregates. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/bi501092p
  • 2015 • 399 The topical use of non-thermal dielectric barrier discharge (DBD): Nitric oxide related effects on human skin
    Heuer, K. and Hoffmanns, M.A. and Demir, E. and Baldus, S. and Volkmar, C.M. and Röhle, M. and Fuchs, P.C. and Awakowicz, P. and Suschek, C.V. and Opländer, C.
    Nitric Oxide - Biology and Chemistry 44 52-60 (2015)
    Dielectric barrier discharge (DBD) devices generate air plasma above the skin containing active and reactive species including nitric oxide (NO). Since NO plays an essential role in skin physiology, a topical application of NO by plasma may be useful in the treatment of skin infections, impaired microcirculation and wound healing. Thus, after safety assessments of plasma treatment using human skin specimen and substitutes, NO-penetration through the epidermis, the loading of skin tissue with NO-derivates in vitro and the effects on human skin in vivo were determined. After the plasma treatment (0-60 min) of skin specimen or reconstructed epidermis no damaging effects were found (TUNEL/MTT). By Franz diffusion cell experiments plasma-induced NO penetration through epidermis and dermal enrichment with NO related species (nitrite 6-fold, nitrate 7-fold, nitrosothiols 30-fold) were observed. Furthermore, skin surface was acidified ( ~ pH 2.7) by plasma treatment (90 s). Plasma application on the forearms of volunteers increased microcirculation fourfold in 1-2 mm and twofold in 6-8 mm depth in the treated skin areas. Regarding the NO-loading effects, skin acidification and increase in dermal microcirculation, plasma devices represent promising tools against chronic/infected wounds. However, efficacy of plasma treatment needs to be quantified in further studies and clinical trials. © 2014 Elsevier Inc. All rights reserved.
    view abstractdoi: 10.1016/j.niox.2014.11.015
  • 2015 • 398 Shape-memory PVDF exhibiting switchable piezoelectricity
    Hoeher, R. and Raidt, T. and Novak, N. and Katzenberg, F. and Tiller, J.C.
    Macromolecular Rapid Communications 36 2042-2046 (2015)
    In this study, a material is designed which combines the properties of shape-memory and electroactive polymers. This is achieved by covalent cross-linking of polyvinylidene fluoride. The resulting polymer network exhibits excellent shape-memory properties with a storable strain of 200%, and fixity as well as recovery values of 100%. Programming upon rolling induces the transformation from the nonelectroactive α-phase to the piezoelectric β-phase. The highest β-phase content is found to be 83% for a programming strain of 200% affording a d33 value of -30 pm V-1. This is in good accordance with literature known values for piezoelectric properties. Thermal triggering this material does not only result in a shape change but also renders the material nonelectroactive. Cross-linking of polyvinylidene fluoride results in a polymer network that combines excellent shape-memory properties with a switchable piezoelectricity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/marc.201500410
  • 2015 • 397 Tectonics of a K+ channel: The importance of the N-terminus for channel gating
    Hoffgaard, F. and Kast, S.M. and Moroni, A. and Thiel, G. and Hamacher, K.
    Biochimica et Biophysica Acta - Biomembranes 1848 3197-3204 (2015)
    The small K+ channel Kcv represents the pore module of complex potassium channels. It was found that its gating can be modified by sensor domains, which are N-terminally coupled to the pore. This implies that the short N-terminus of the channel can transmit conformational changes from upstream sensors to the channel gates. To understand the functional role of the N-terminus in the context of the entire channel protein, we apply combinatorial screening of the mechanical coupling and long-range interactions in the Kcv potassium channel by reduced molecular models. The dynamics and mechanical connections in the channel complex show that the N-terminus is indeed mechanically connected to the pore domain. This includes a long rang coupling to the pore and the inner and outer transmembrane domains. Since the latter domains host the two gates of the channel, the data support the hypothesis that mechanical perturbation of the N-terminus can be transmitted to the channel gates. This effect is solely determined by the topology of the channel; sequence details only have an implicit effect on the coarse-grained dynamics via the fold and not through biochemical details at a smaller scale. This observation has important implications for engineering of synthetic channels on the basis of a K+ channel pore. © 2015 Elsevier B.V.All rights reserved.
    view abstractdoi: 10.1016/j.bbamem.2015.09.015
  • 2015 • 396 Potential-Assisted DNA Immobilization as a Prerequisite for Fast and Controlled Formation of DNA Monolayers
    Jambrec, D. and Gebala, M. and La Mantia, F. and Schuhmann, W.
    Angewandte Chemie - International Edition 54 15064-15068 (2015)
    Highly reproducible and fast potential-assisted immobilization of single-stranded (ss)DNA on gold surfaces is achieved by applying a pulse-type potential modulation. The desired DNA coverage can be obtained in a highly reproducible way within minutes. Understanding the underlying processes occurring during potential-assisted ssDNA immobilization is crucial. We propose a model that considers the role of ions surrounding the DNA strands, the distance dependence of the applied potentials within the electrolyte solution, and most importantly the shift of the potential of zero charge during the immobilization due to the surface modification with DNA. The control of the surface coverage of ssDNA as well as the achieved speed and high reproducibility are seen as prerequisites for improved DNA-based bioassays. Stir it up: The desired DNA coverage can be reached within minutes by stirring the DNA in front of an electrode by means of a pulse-type potential modulation. The mechanism of potential-assisted immobilization can be understood by considering the role of ions surrounding the DNA, the distance over which applied potentials have an impact on DNA, and the shift of the potential of zero charge (pzc) during the immobilization due to DNA immobilization. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201506672
  • 2015 • 395 Associations between three specific a-cellular measures of the oxidative potential of particulate matter and markers of acute airway and nasal inflammation in healthy volunteers
    Janssen, N.A.H. and Strak, M. and Yang, A. and Hellack, B. and Kelly, F.J. and Kuhlbusch, T.A.J. and Harrison, R.M. and Brunekreef, B. and Cassee, F.R. and Steenhof, M. and Hoek, G.
    Occupational and Environmental Medicine 72 49-56 (2015)
    Introduction We evaluated associations between three a-cellular measures of the oxidative potential (OP) of particulate matter (PM) and acute health effects. Methods We exposed 31 volunteers for 5 h to ambient air pollution at five locations: an underground train station, two traffic sites, a farm and an urban background site. Each volunteer visited at least three sites. We conducted health measurements before exposure, 2 h after exposure and the next morning. We measured air pollution on site and characterised the OP of PM2.5 and PM10 using three a-cellular assays; dithiotreitol (OPDTT), electron spin resonance (OPESR) and ascorbic acid depletion (OPAA). Results In single-pollutant models, all measures of OP were significantly associated with increases in fractional exhaled nitric oxide and increases in interleukin-6 in nasal lavage 2 h after exposure. These OP associations remained significant after adjustment for co-pollutants when only the four outdoor sites were included, but lost significance when measurements at the underground site were included. Other health end points including lung function and vascular inflammatory and coagulation parameters in blood were not consistently associated with OP. Conclusions We found significant associations between three a-cellular measures of OP of PM and markers of airway and nasal inflammation. However, consistency of these effects in two-pollutant models depended on how measurements at the underground site were considered. Lung function and vascular inflammatory and coagulation parameters in blood were not consistently associated with OP. Our study, therefore, provides limited support for a role of OP in predicting acute health effects of PM in healthy young adults.
    view abstractdoi: 10.1136/oemed-2014-102303
  • 2015 • 394 A novel approach for analyzing the dissolution mechanism of solid dispersions
    Ji, Y. and Paus, R. and Prudic, A. and Lübbert, C. and Sadowski, G.
    Pharmaceutical Research 32 2559-2578 (2015)
    Purpose To analyze the dissolution mechanism of solid dispersions of poorly water-soluble active pharmaceutical ingredients (APIs), to predict the dissolution profiles of the APIs and to find appropriate ways to improve their dissolution rate. Methods The dissolution profiles of indomethacin and naproxen from solid dispersions in PVP K25 were measured in vitro using a rotating-disk system (USP II). A chemical-potential-gradient model combined with the thermodynamic model PC-SAFT was developed to investigate the dissolution mechanism of indomethacin and naproxen from their solid dispersions at different conditions and to predict the dissolution profiles of these APIs. Results The results show that the dissolution of the investigated solid dispersions is controlled by dissolution of both, API and PVP K25 as they codissolve according to the initial API loading. Moreover, the dissolution of indomethacin and naproxen was improved by decreasing the API loading in polymer (leading to amorphous solid dispersions) and increasing stirring speed, temperature and pH of the dissolution medium. The dissolution of indomethacin and naproxen from their amorphous solid dispersions is mainly controlled by the surface reaction, which implies that indomethacin and naproxen dissolution can be effectively improved by formulation design and by improving their solvation performance. Conclusions The chemical-potential-gradient model combined with PC-SAFTcan be used to analyze the dissolution mechanism of solid dispersions and to describe and predict the dissolution profiles of API as function of stirring speed, temperature and pH value of the medium. This work helps to find appropriate ways to improve the dissolution rate of poorly-soluble APIs. © Springer Science+Business Media New York 2015.
    view abstractdoi: 10.1007/s11095-015-1644-z
  • 2015 • 393 Unraveling the interactions between cold atmospheric plasma and skin-components with vibrational microspectroscopy
    Kartaschew, K. and Mischo, M. and Baldus, S. and Bründermann, E. and Awakowicz, P. and Havenith, M.
    Biointerphases 10 (2015)
    Using infrared and Raman microspectroscopy, the authors examined the interaction of cold atmospheric plasma with the skin's built-in protective cushion, the outermost skin layer stratum corneum. Following a spectroscopic analysis, the authors could identify four prominent chemical alterations caused by plasma treatment: (1) oxidation of disulfide bonds in keratin leading to a generation of cysteic acid; (2) formation of organic nitrates as well as (3) of new carbonyl groups like ketones, aldehydes and acids; and (4) reduction of double bonds in the lipid matter lanolin, which resembles human sebum. The authors suggest that these generated acidic and NO-containing functional groups are the source of an antibacterial and regenerative environment at the treatment location of the stratum corneum. Based upon the author's results, the authors propose a mechanistic view of how cold atmospheric plasmas could modulate the skin chemistry to produce positive long-term effects on wound healing: Briefly, cold atmospheric plasmas have the potential to transform the skin itself into a therapeutic resource. © 2015 American Vacuum Society.
    view abstractdoi: 10.1116/1.4919610
  • 2015 • 392 High-Speed GaN/GaInN Nanowire Array Light-Emitting Diode on Silicon(111)
    Koester, R. and Sager, D. and Quitsch, W.-A. and Pfingsten, O. and Poloczek, A. and Blumenthal, S. and Keller, G. and Prost, W. and Bacher, G. and Tegude, F.-J.
    Nano Letters 15 2318-2323 (2015)
    (Graph Presented). The high speed on-off performance of GaN-based light-emitting diodes (LEDs) grown in c-plane direction is limited by long carrier lifetimes caused by spontaneous and piezoelectric polarization. This work demonstrates that this limitation can be overcome by m-planar core-shell InGaN/GaN nanowire LEDs grown on Si(111). Time-resolved electroluminescence studies exhibit 90-10% rise- and fall-times of about 220 ps under GHz electrical excitation. The data underline the potential of these devices for optical data communication in polymer fibers and free space. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/nl504447j
  • 2015 • 391 Perfluorodecalin-filled Poly(n-butyl-cyanoacrylate) nanocapsules as potential artificial oxygen carriers: Preclinical safety and biocompatibility
    Laudien, J. and Groß-Heitfeld, C. and Mayer, C. and De Groot, H. and Kirsch, M. and Ferenz, K.B.
    Journal of Nanoscience and Nanotechnology 15 5637-5648 (2015)
    With regard to the development of artificial blood substitutes, perfluorodecalin-filled poly(n-butyl-cyanoacrylate) nanocapsules are already discussed for the use as artificial oxygen carriers. The aim of the present study was to thoroughly investigate the preclinical safety and biocompatibility of the perfluorodecalin-filled poly(n-butyl-cyanoacrylate) nanocapsules prepared by interfacial polymerization. Nanocapsules were assessed for physical and microbial stability. Subsequent to intravenous infusion to anesthetized rats, effects on systemic parameters, microcirculation, circulatory in vivo half-life, acid base/metabolic status, organ damage and biodistribution were evaluated using inter alia 19F-NMR spectroscopy and in vivo microscopy. Perfluorodecalin-filled poly (n-butyl-cyanoacrylate) nanocapsules displayed physical and microbianl stability over a period of 4 weeks and the circulatory in vivo half-life was t1/2 = 30 min. In general, all animals tolerated intravenous infusion of the prepared nanocapsules, even though several side-effects occurred. As a consequence of nanocapsule infusion, a transient decrease in mean arterial blood pressure, impairment of hepatic microcirculation, organ/tissue damage of liver, spleen and small intestine, as well as an elevation of plasma enzyme activities such as lactate dehydrogenase, creatine kinase and aspartate aminotransferase could be observed. The assessment of the distribution pattern revealed nanocapsule accumulation in spleen, kidney and small intestine. Perfluorodecalin-filled poly(n-butyl-cyanoacrylate) nanocapsules conformed to basic requirements of drugs under preclinical development but further improvement is needed to establish these nanocapsules as novel artificial oxygen carriers. Copyright © 2015 American Scientific Publishers All rights reserved.
    view abstractdoi: 10.1166/jnn.2015.10044
  • 2015 • 390 Development of sustained and dual drug release co-extrusion formulations for individual dosing
    Laukamp, E.J. and Vynckier, A.-K. and Voorspoels, J. and Thommes, M. and Breitkreutz, J.
    European Journal of Pharmaceutics and Biopharmaceutics 89 357-364 (2015)
    In personalized medicine and patient-centered medical treatment individual dosing of medicines is crucial. The Solid Dosage Pen (SDP) allows for an individual dosing of solid drug carriers by cutting them into tablet-like slices. The aim of the present study was the development of sustained release and dual release formulations with carbamazepine (CBZ) via hot-melt co-extrusion for the use in the SDP. The selection of appropriate coat- and core-formulations was performed by adapting the mechanical properties (like tensile strength and E-modulus) for example. By using different excipients (polyethylene glycols, poloxamers, white wax, stearic acid, and carnauba wax) and drug loadings (30-50%) tailored dissolution kinetics was achieved showing cube root or zero order release mechanisms. Besides a biphasic drug release, the dose-dependent dissolution characteristics of sustained release formulations were minimized by a co-extruded wax-coated formulation. The dissolution profiles of the co-extrudates were confirmed during short term stability study (six months at 21.0 ± 0.2 °C, 45% r.h.). Due to a good layer adhesion of core and coat and adequate mechanical properties (maximum cutting force of 35.8 ± 2.0 N and 26.4 ± 2.8 N and E-modulus of 118.1 ± 8.4 and 33.9 ± 4.5 MPa for the dual drug release and the wax-coated co-extrudates, respectively) cutting off doses via the SDP was precise. While differences of the process parameters (like the barrel temperature) between the core- and the coat-layer resulted in unsatisfying content uniformities for the wax-coated co-extrudates, the content uniformity of the dual drug release co-extrudates was found to be in compliance with pharmacopoeial specification. © 2015 Elsevier B.V. All rights reserved.
    view abstractdoi: 10.1016/j.ejpb.2014.12.027
  • 2015 • 389 3 Tesla high-resolution and delayed gadolinium enhanced MR imaging of cartilage (dGEMRIC) after autologous chondrocyte transplantation in the hip
    Lazik, A. and Körsmeier, K. and Claßen, T. and Jäger, M. and Kamminga, M. and Kraff, O. and Lauenstein, T.C. and Theysohn, J.M. and Landgraeber, S.
    Journal of Magnetic Resonance Imaging 42 624-633 (2015)
    Background To evaluate the feasibility of 3 Tesla (T) high-resolution and gadolinium enhanced MRI of cartilage (dGEMRIC) in the thin and rounded hip cartilage of patients after acetabular matrix-based autologous chondrocyte transplantation (MACT). Methods Under general ethics approval, 24 patients were prospectively examined 6-31 months after acetabular MACT at 3T using high-resolution proton-density weighted (PDw) images (bilateral PD SPACE, 0.8 mm isotropic; unilateral PD-TSE coronal/sagittal, 0.8 × 0.8 resp. 0.5 × 0.5 × 2.5 mm) as well as T1 mapping (3D-FLASH, 0.78 mm isotropic) in dGEMRIC technique, and clinically scored. The cartilage transplant was evaluated using an adapted MOCART score (maximum 85 points). T1 relaxation times were measured independently by two radiologists. Here, regions of interest were placed manually in automatically calculated relaxation-maps, both in the transplant and adjacent healthy cartilage regions. Interobserver reliability was estimated by means of intraclass-correlation (ICC). Results The transplant was morphologically definable in the PDw images of 23 patients with a mean MOCART score of 69 points (60-80 points, SD 6.5). T1 maps showed a clear differentiation between acetabular and femoral cartilage, but correlation with PDw images was necessary to identify the transplant. Mean T1 relaxation times of the transplant were 616.3 ms (observer 1) resp. 610.1 ms (observer 2), and of adjacent healthy acetabular cartilage 574.5 ms (observer 1) resp. 604.9 ms (observer 2). Interobserver reliability of the relaxation times in the transplant was excellent (ICC-coefficient 0.88) and in adjacent healthy regions good (0.77). Conclusion High-resolution PDw imaging with adapted MOCART scoring and dGEMRIC is feasible after MACT in the thin and rounded hip cartilage. J. Magn. Reson. Imaging 2015;42:624-633. © 2014 Wiley Periodicals, Inc.
    view abstractdoi: 10.1002/jmri.24821
  • 2015 • 388 A tailor-made specific anion-binding motif in the side chain transforms a tetrapeptide into an efficient vector for gene delivery
    Li, M. and Schlesiger, S. and Knauer, S.K. and Schmuck, C.
    Angewandte Chemie - International Edition 54 2941-2944 (2015)
    Arginine-rich cell-penetrating peptides are widely utilized as vectors for gene delivery. However, their transfection efficacy still needs to be optimized. To accomplish this, guanidinocarbonylpyrrole groups, which are tailor-made anion binding sites, were introduced into the side chains of tetralysine to obtain the peptide analogue 1. In contrast to the common strategy of adding a lipophilic tail to peptide vectors, this novel method most likely enhances transfection efficacy through more specific interactions between the binding motifs and DNA or the cell membrane. Tetrapeptide analogue 1 is thus the smallest peptidic transfection vector that has been reported to date. The transfection efficacy of 1, which on average has less than two positive charges under physiological conditions, is even better than that of polyethylenimine (PEI). Furthermore, 1 exhibits only negligible cytotoxicity, which makes it an interesting candidate for further development. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA.
    view abstractdoi: 10.1002/anie.201410429
  • 2015 • 387 Continuous delivery of rhBMP2 and rhVEGF165 at a certain ratio enhances bone formation in mandibular defects over the delivery of rhBMP2 alone - An experimental study in rats
    Lohse, N. and Moser, N. and Backhaus, S. and Annen, T. and Epple, M. and Schliephake, H.
    Journal of Controlled Release 220 201-209 (2015)
    The aim of the present study was to test the hypothesis that different amounts of vascular endothelial growth factor and bone morphogenic protein differentially affect bone formation when applied for repair of non-healing defects in the rat mandible. Porous composite PDLLA/CaCO3 carriers were fabricated as slow release carriers and loaded with rhBMP2 and rhVEGF165 in 10 different dosage combinations using gas foaming with supercritical carbon dioxide. They were implanted in non-healing defects of the mandibles of 132 adult Wistar rats with additional lateral augmentation. Bone formation was assessed both radiographically (bone volume) and by histomorphometry (bone density). The use of carriers with a ratio of delivery of VEGF/BMP between 0.7 and 1.2 was significantly related to the occurrence of significant increases in radiographic bone volume and/or histologic bone density compared to the use of carriers with a ratio of delivery of ≤ 0.5 when all intervals and all outcome parameters were considered. Moreover, simultaneous delivery at this ratio helped to "save" rhBMP2 as both bone volume and bone density after 13 weeks were reached/surpassed using half the dosage required for rhBMP2 alone. It is concluded, that the combined delivery of rhVEGF165 and rhBMP2 for repair of critical size mandibular defects can significantly enhance volume and density of bone formation over delivery of rhBMP2 alone. It appears from the present results that continuous simultaneous delivery of rhVEGF165 and rhBMP2 at a ratio of approximately 1 is favourable for the enhancement of bone formation. © 2015 Published by Elsevier B.V.
    view abstractdoi: 10.1016/j.jconrel.2015.10.032
  • 2015 • 386 Molecular Tweezers Inhibit Islet Amyloid Polypeptide Assembly and Toxicity by a New Mechanism
    Lopes, D.H.J. and Attar, A. and Nair, G. and Hayden, E.Y. and Du, Z. and McDaniel, K. and Dutt, S. and Bandmann, H. and Bravo-Rodriguez, K. and Mittal, S. and Klärner, F.-G. and Wang, C. and Sanchez-Garcia, E. and Schrader, T. an...
    ACS Chemical Biology 10 1555-1569 (2015)
    In type-2 diabetes (T2D), islet amyloid polypeptide (IAPP) self-associates into toxic assemblies causing islet β-cell death. Therefore, preventing IAPP toxicity is a promising therapeutic strategy for T2D. The molecular tweezer CLR01 is a supramolecular tool for selective complexation of K residues in (poly)peptides. Surprisingly, it inhibits IAPP aggregation at substoichiometric concentrations even though IAPP has only one K residue at position 1, whereas efficient inhibition of IAPP toxicity requires excess CLR01. The basis for this peculiar behavior is not clear. Here, a combination of biochemical, biophysical, spectroscopic, and computational methods reveals a detailed mechanistic picture of the unique dual inhibition mechanism for CLR01. At low concentrations, CLR01 binds to K1, presumably nucleating nonamyloidogenic, yet toxic, structures, whereas excess CLR01 binds also to R11, leading to nontoxic structures. Encouragingly, the CLR01 concentrations needed for inhibition of IAPP toxicity are safe in vivo, supporting its development toward disease-modifying therapy for T2D. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/acschembio.5b00146
  • 2015 • 385 A molecular tweezer antagonizes seminal amyloids and HIV infection
    Lump, E. and Castellano, L.M. and Meier, C. and Seeliger, J. and Erwin, N. and Sperlich, B. and Stürzel, C.M. and Usmani, S. and Hammond, R.M. and Von Einem, J. and Gerold, G. and Kreppel, F. and Bravo-Rodriguez, K. and Pietschma...
    eLife 4 (2015)
    Semen is the main vector for HIV transmission and contains amyloid fibrils that enhance viral infection. Available microbicides that target viral components have proven largely ineffective in preventing sexual virus transmission. In this study, we establish that CLR01, a ‘molecular tweezer’ specific for lysine and arginine residues, inhibits the formation of infectivity-enhancing seminal amyloids and remodels preformed fibrils. Moreover, CLR01 abrogates semen-mediated enhancement of viral infection by preventing the formation of virion–amyloid complexes and by directly disrupting the membrane integrity of HIV and other enveloped viruses.We establish that CLR01 acts by binding to the target lysine and arginine residues rather than by a non-specific, colloidal mechanism. CLR01 counteracts both host factors that may be important for HIV transmission and the pathogen itself. These combined anti-amyloid and antiviral activities make CLR01 a promising topical microbicide for blocking infection by HIV and other sexually transmitted viruses. © 2015, Lump et al.
    view abstractdoi: 10.7554/eLife.05397
  • 2015 • 384 Toxicity Inhibitors Protect Lipid Membranes from Disruption by Aβ42
    Malishev, R. and Nandi, S. and Kolusheva, S. and Levi-Kalisman, Y. and Klärner, F.-G. and Schrader, T. and Bitan, G. and Jelinek, R.
    ACS Chemical Neuroscience 6 1860-1869 (2015)
    Although the precise molecular factors linking amyloid β-protein (Aβ) to Alzheimer's disease (AD) have not been deciphered, interaction of Aβ with cellular membranes has an important role in the disease. However, most therapeutic strategies targeting Aβ have focused on interfering with Aβ self-assembly rather than with its membrane interactions. Here, we studied the impact of three toxicity inhibitors on membrane interactions of Aβ42, the longer form of Aβ, which is associated most strongly with AD. The inhibitors included the four-residue C-terminal fragment Aβ(39-42), the polyphenol (-)-epigallocatechin-3-gallate (EGCG), and the lysine-specific molecular tweezer, CLR01, all of which previously were shown to disrupt different steps in Aβ42 self-assembly. Biophysical experiments revealed that incubation of Aβ42 with each of the three modulators affected membrane interactions in a distinct manner. Interestingly, EGCG and CLR01 were found to have significant interaction with membranes themselves. However, membrane bilayer disruption was reduced when the compounds were preincubated with Aβ42, suggesting that binding of the assembly modulators to the peptide attenuated their membrane interactions. Importantly, our study reveals that even though the three tested compounds affect Aβ42 assembly differently, membrane interactions were significantly inhibited upon incubation of each compound with Aβ42, suggesting that preventing the interaction of Aβ42 with the membrane contributes substantially to inhibition of its toxicity by each compound. The data suggest that interference with membrane interactions is an important factor for Aβ42 toxicity inhibitors and should be taken into account in potential therapeutic strategies, in addition to disruption or remodeling of amyloid assembly. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/acschemneuro.5b00200
  • 2015 • 383 Assembling Paramagnetic Ceruloplasmin at Electrode Surfaces Covered with Ferromagnetic Nanoparticles. Scanning Electrochemical Microscopy in the Presence of a Magnetic Field
    Matysiak, E. and Botz, A.J.R. and Clausmeyer, J. and Wagner, B. and Schuhmann, W. and Stojek, Z. and Nowicka, A.M.
    Langmuir 31 8176-8183 (2015)
    Adsorption of ceruloplasmin (Cp) at a gold electrode modified with ferromagnetic iron nanoparticles encapsulated in carbon (Fe@C Nps) leads to a successful immobilization of the enzyme in its electroactive form. The proper placement of Cp at the electrode surface on top of the nanocapsules containing an iron core allowed a preorientation of the enzyme, hence allowing direct electron transfer between the electrode and the enzyme. Laser ablation coupled with inductively coupled plasma mass spectrometry indicated that Cp was predominantly located at the paramagnetic nanoparticles. Scanning electrochemical microscopy measurements in the sample-generation/tip-collection mode proved that Cp was ferrooxidative inactive if it was immobilized on the bare gold surface and reached the highest activity if it was adsorbed on Fe@C Nps in the presence of a magnetic field. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/acs.langmuir.5b01155
  • 2015 • 382 Periodic Vesicle Formation in Tectonic Fault Zones—an Ideal Scenario for Molecular Evolution
    Mayer, C. and Schreiber, U. and Dávila, M.J.
    Origins of Life and Evolution of Biospheres 45 139-148 (2015)
    Tectonic fault systems in the continental crust offer huge networks of interconnected channels and cavities. Filled mainly with water and carbon dioxide (CO<inf>2</inf>), containing a wide variety of hydrothermal chemistry and numerous catalytic surfaces, they may offer ideal reaction conditions for prebiotic chemistry. In these systems, an accumulation zone for organic compounds will develop at a depth of approximately 1 km where CO<inf>2</inf> turns sub-critical and dissolved components precipitate. At this point, periodic pressure changes caused for example by tidal influences or geyser activity may generate a cyclic process involving repeated phase transitions of carbon dioxide. In the presence of amphiphilic compounds, this will necessarily lead to the transient formation of coated water droplets in the gas phase and corresponding vesicular structures in the aqueous environment. During this process, the concentration of organic components inside the droplets and vesicles would be drastically increased, allowing for favorable reaction conditions and, in case of the vesicles generated, large trans-membrane concentration gradients. Altogether, the process of periodic formation and destruction of vesicles could offer a perfect environment for molecular evolution in small compartments and for the generation of protocells. The basic process of vesicle formation is reproduced experimentally with a lipid in a water/CO<inf>2</inf> system. © 2015, The Author(s).
    view abstractdoi: 10.1007/s11084-015-9411-z
  • 2015 • 381 Monitoring ligand-induced conformational changes for the identification of estrogen receptor agonists and antagonists
    Mayer-Wrangowski, S.C. and Rauh, D.
    Angewandte Chemie - International Edition 54 4379-4382 (2015)
    Nuclear receptors are transcription factors that are important targets for current drug discovery efforts as they play a role in many pathological processes. Their activity can be regulated by small molecules like hormones and drugs that can have agonistic or antagonistic functions. These ligands bind to the receptor and account for diverse conformational changes that are crucial determinants for the receptor activity. Here, we set out to develop FLiN (fluorescent labels in nuclear receptors), a direct binding assay that detects conformational changes in the estrogen receptor. The assay is based on the introduction of a cysteine residue and subsequent specific labeling of the receptor with a thiol-reactive fluorophore. Changes in the receptor conformation upon ligand binding lead to differences in the microenvironment of the fluorophore and alter its emission spectrum. The FLiN assay distinguishes between different binding modes and is suitable for high-throughput screening. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201410148
  • 2015 • 380 Simplified formulations with high drug loads for continuous twin-screw granulation
    Meier, R. and Thommes, M. and Rasenack, N. and Krumme, M. and Moll, K.-P. and Kleinebudde, P.
    International Journal of Pharmaceutics 496 12-23 (2015)
    As different batches of the same excipients will be intermixed during continuous processes, the traceability of batches is complicated. Simplified formulations may help to reduce problems related to batch intermixing and traceability. Twin-screw granulation with subsequent tableting was used to produce granules and tablets, containing drug, disintegrant and binder (binary and ternary mixtures), only. Drug loads up to 90% were achieved and five different disintegrants were screened for keeping their disintegration suitability after wetting. Granule size distributions were consistently mono-modal and narrow. Granule strength reached higher values, using ternary mixtures. Tablets containing croscarmellose-Na as disintegrant displayed tensile strengths up to 3.1 MPa and disintegration times from 400 to 466 s, resulting in the most robust disintegrant. Dissolution was overall complete and above 96% within 30 min. Na-starch glycolate offers tensile strengths up to 2.8 MPa at disintegration times from 25 s to 1031 s, providing the broadest application window, as it corresponds in some parts to different definitions of orodispersible tablets. Tablets containing micronized crospovidone are not suitable for immediate release, but showed possibilities to produce highly drug loaded, prolonged release tablets. Tablets and granules from simplified formulations offer great opportunities to improve continuous processes, present performances comparable to more complicated formulations and are able to correspond to requirements of the authorities. © 2015 Elsevier B.V. All rights reserved.
    view abstractdoi: 10.1016/j.ijpharm.2015.05.060
  • 2015 • 379 High-throughput screening of thin-film semiconductor material libraries II: Characterization of Fe-W-O libraries
    Meyer, R. and Sliozberg, K. and Khare, C. and Schuhmann, W. and Ludwig, Al.
    ChemSusChem 8 1279-1285 (2015)
    Metal oxides are promising materials for solar water splitting. To identify suitable materials within the ternary system Fe-W-O, thin-film material libraries with combined thickness and compositional gradients were synthesized by combinatorial reactive magnetron sputtering. These libraries (>1000 different samples) were investigated by means of structural and functional high-throughput characterization techniques to establish correlations between composition, crystallinity, morphology, thickness, and photocurrent density in the compositional range between (Fe<inf>6</inf>W<inf>94</inf>)O<inf>x</inf> and (Fe<inf>61</inf>W<inf>39</inf>)O<inf>x</inf>. In addition to the well-known phase WO<inf>3</inf>, the binary phase W<inf>5</inf>O<inf>14</inf> and the ternary phase Fe<inf>2</inf>O<inf>6</inf>W show enhanced photoelectrochemical activity. The highest photocurrent density of 65 μA cm-2 was achieved for the composition (Fe<inf>15</inf>W<inf>85</inf>)O<inf>x</inf>, which contains the W<inf>5</inf>O<inf>14</inf> phase and has a thickness of 1060 nm. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.201402918
  • 2015 • 378 Impact of bacterial endotoxin on the structure of DMPC membranes
    Nagel, M. and Brauckmann, S. and Moegle-Hofacker, F. and Effenberger-Neidnicht, K. and Hartmann, M. and De Groot, H. and Mayer, C.
    Biochimica et Biophysica Acta - Biomembranes 1848 2271-2276 (2015)
    Abstract Bacterial lipopolysaccharides are believed to have a toxic effect on human cell membranes. In this study, the influence of a lipopolysaccharide (LPS) from Escherichia coli on the structure, the dynamics and the mechanical strength of phospholipid membranes are monitored by nuclear magnetic resonance spectroscopy (NMR) and by atomic force microscopy (AFM). Model membranes are formed from 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and are either prepared as multilamellar bulk samples or multilamellar vesicles. Field gradient NMR data directly prove the rapid integration of LPS into DMPC membranes. Solid state NMR experiments primarily detect decreasing molecular order parameters with increasing LPS content. This is accompanied by a mechanical softening of the membrane bilayers as is shown by AFM indentation measurements. Altogether, the data prove that lipopolysaccharide molecules quickly insert into phospholipid bilayers, increase membrane fluctuation amplitudes and significantly weaken their mechanical stiffness. © 2015 Published by Elsevier B.V.
    view abstractdoi: 10.1016/j.bbamem.2015.06.008
  • 2015 • 377 Mobility of coated and uncoated TiO2 nanomaterials in soil columns - Applicability of the tests methods of OECD TG 312 and 106 for nanomaterials
    Nickel, C. and Gabsch, S. and Hellack, B. and Nogowski, A. and Babick, F. and Stintz, M. and Kuhlbusch, T.A.J.
    Journal of Environmental Management 157 230-237 (2015)
    Nanomaterials are commonly used in everyday life products and during their life cycle they can be released into the environment. Soils and sediments are estimated as significant sinks for those nanomaterials. To investigate and assess the behaviour of nanomaterials in soils and sediments standardized test methods are needed. In this study the applicability of two existing international standardized test guidelines for the testing of nanomaterials, OECD TG 106 "Adsorption/Desorption using a Bath Equilibrium Method" and the OECD TG 312 "Leaching in Soil Columns", were investigated. For the study one coated and two uncoated TiO<inf>2</inf> nanomaterials were used, respectively. The results indicate that the OECD TG 106 is not applicable for nanomaterials. However, the test method according to OECD TG 312 was found to be applicable if nano-specific adaptations are applied. The mobility investigations of the OECD TG 312 indicated a material-dependent mobility of the nanomaterials, which in some cases may lead to an accumulation in the upper soil layers. Whereas no significant transport was observed for the uncoated materials for the double-coated material (coating with dimethicone and aluminiumoxide) a significant transport was detected and attributed to the coating. © 2015 Elsevier Ltd.
    view abstractdoi: 10.1016/j.jenvman.2015.04.029
  • 2015 • 376 A Redox Hydrogel Protects the O2-Sensitive [FeFe]-Hydrogenase from Chlamydomonas reinhardtii from Oxidative Damage
    Oughli, A.A. and Conzuelo, F. and Winkler, M. and Happe, T. and Lubitz, W. and Schuhmann, W. and Rüdiger, O. and Plumeré, N.
    Angewandte Chemie - International Edition 54 12329-12333 (2015)
    The integration of sensitive catalysts in redox matrices opens up the possibility for their protection from deactivating molecules such as O2. [FeFe]-hydrogenases are enzymes catalyzing H2 oxidation/production which are irreversibly deactivated by O2. Therefore, their use under aerobic conditions has never been achieved. Integration of such hydrogenases in viologen-modified hydrogel films allows the enzyme to maintain catalytic current for H2 oxidation in the presence of O2, demonstrating a protection mechanism independent of reactivation processes. Within the hydrogel, electrons from the hydrogenase-catalyzed H2 oxidation are shuttled to the hydrogel-solution interface for O2 reduction. Hence, the harmful O2 molecules do not reach the hydrogenase. We illustrate the potential applications of this protection concept with a biofuel cell under H2/O2 mixed feed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201502776
  • 2015 • 375 Predicting the Solubility Advantage of Amorphous Pharmaceuticals: A Novel Thermodynamic Approach
    Paus, R. and Ji, Y. and Vahle, L. and Sadowski, G.
    Molecular Pharmaceutics 12 2823-2833 (2015)
    For the solubility and bioavailability of poorly soluble active pharmaceutical ingredients (APIs) to be improved, the transformation of crystalline APIs to the amorphous state has often been shown to be advantageous. As it is often difficult to measure the solubility of amorphous APIs, the application of thermodynamic models is the method of choice for determining the solubility advantage. In this work, the temperature-dependent solubility advantage of an amorphous API versus its crystalline form was predicted for five poorly soluble APIs in water (glibenclamide, griseofulvin, hydrochlorothiazide, indomethacin, and itraconazole) based on modeling the API/solvent phase diagrams using the perturbed-chain statistical associating fluid theory (PC-SAFT). Evaluation of the performance of this approach was performed by comparing the predicted solubility advantage to experimental data and to the solubility advantage calculated by the commonly applied Gibbs-energy-difference method. For all of the systems considered, PC-SAFT predictions of the solubility advantage are significantly more accurate than the results obtained from the Gibbs-energy-difference method. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/mp500824d
  • 2015 • 374 Spheronization of solid lipid extrudates: A novel approach on controlling critical process parameters
    Petrovick, G.F. and Pein, M. and Thommes, M. and Breitkreutz, J.
    European Journal of Pharmaceutics and Biopharmaceutics 92 15-21 (2015)
    Solid lipids are non-toxic excipients, which are known to potentially enhance delivery and bioavailability of poorly water-soluble drugs and moreover to mask unpleasant tasting drugs. Multiple unit matrix dosage forms based on solid lipids, such as lipid pellets, can be obtained by solvent-free cold extrusion and spheronization. This method presents advantages in the processing of sensitive substances, such as low process temperatures, the absence of solvents and a drying step. However, the material temperature during the spheronization showed to be critical so far. The process leads to increased material temperatures, causing particle agglomeration and discontinuity of the spheronization. In the present study, extrudates of 0.5 mm in diameter containing metformin hydrochloride, and either semisynthetic hard fat (Witocan® 42/44) or different ternary mixtures based on hard fat, glyceryl trimyristate, and glyceryl distearate, were spheronized. By applying common process parameters, particle agglomeration or material stickiness on equipment walls was observed in preliminary experiments after 2-6 min, depending on the lipid composition. Therefore, an innovative instrumental setup to control the spheronization process was developed utilizing an infrared light source, which was positioned over the particle bed. The new approach enabled a spheronization process that reached the desired spheronization temperature after 2-3 min and neither particle agglomeration nor material adherence occurred even after longer process times. The different formulations, even those based on high amount of solid lipids, were successfully spheronized over 15 min, resulting in small diameter lipid pellets with smooth surface and aspect ratios below 1.3. © 2015 Elsevier B.V. All rights reserved.
    view abstractdoi: 10.1016/j.ejpb.2015.02.004
  • 2015 • 373 Coupling of an enzymatic biofuel cell to an electrochemical cell for self-powered glucose sensing with optical readout
    Pinyou, P. and Conzuelo, F. and Sliozberg, K. and Vivekananthan, J. and Contin, A. and Pöller, S. and Plumeré, N. and Schuhmann, W.
    Bioelectrochemistry 106 22-27 (2015)
    A miniaturized biofuel cell (BFC) is powering an electrolyser invoking a glucose concentration dependent formation of a dye which can be determined spectrophotometrically. This strategy enables instrument free analyte detection using the analyte-dependent BFC current for triggering an optical read-out system. A screen-printed electrode (SPE) was used for the immobilization of the enzymes glucose dehydrogenase (GDH) and bilirubin oxidase (BOD) for the biocatalytic oxidation of glucose and reduction of molecular oxygen, respectively. The miniaturized BFC was switched-on using small sample volumes (ca. 60μL) leading to an open-circuit voltage of 567mV and a maximal power density of (6.8±0.6) μWcm-2. The BFC power was proportional to the glucose concentration in a range from 0.1 to 1.0mM (R2=0.991). In order to verify the potential instrument-free analyte detection the BFC was directly connected to an electrochemical cell comprised of an optically-transparent SPE modified with methylene green (MG). The reduction of the electrochromic reporter compound invoked by the voltage and current flow applied by the BFC let to MG discoloration, thus allowing the detection of glucose. © 2015 Elsevier B.V..
    view abstractdoi: 10.1016/j.bioelechem.2015.04.003
  • 2015 • 372 Determinants of amyloid fibril degradation by the PDZ protease HTRA1
    Poepsel, S. and Sprengel, A. and Saccà, B. and Kaschani, F. and Kaiser, M. and Gatsogiannis, C. and Raunser, S. and Clausen, T. and Ehrmann, M.
    Nature Chemical Biology 11 862-869 (2015)
    Excessive aggregation of proteins has a major impact on cell fate and is a hallmark of amyloid diseases in humans. To resolve insoluble deposits and to maintain protein homeostasis, all cells use dedicated protein disaggregation, protein folding and protein degradation factors. Despite intense recent research, the underlying mechanisms controlling this key metabolic event are not well understood. Here, we analyzed how a single factor, the highly conserved serine protease HTRA1, degrades amyloid fibrils in an ATP-independent manner. This PDZ protease solubilizes protein fibrils and disintegrates the fibrillar core structure, allowing productive interaction of aggregated polypeptides with the active site for rapid degradation. The aggregate burden in a cellular model of cytoplasmic tau aggregation is thus reduced. Mechanistic aspects of ATP-independent proteolysis and its implications in amyloid diseases are discussed. © 2015 Nature America, Inc. All rights reserved.
    view abstractdoi: 10.1038/nchembio.1931
  • 2015 • 371 On the mechanism of nanoparticle formation in a flame doped by iron pentacarbonyl
    Poliak, M. and Fomin, A. and Tsionsky, V. and Cheskis, S. and Wlokas, I. and Rahinov, I.
    Physical Chemistry Chemical Physics 17 680-685 (2015)
    In this work we have investigated the mechanism of nanoparticle synthesis in a low pressure, premixed, laminar flat flame of CH4-O2, doped with iron pentacarbonyl using a combined quartz-crystal-microbalance-particle-mass-spectrometry apparatus. We have unambiguously demonstrated that the formation of nanoparticles in iron pentacarbonyl-doped flames occurs very early, in close proximity to the burner surface, prior to the flame front. This early rise of nanoparticle mass concentration is followed by a sharp drop in nanoparticle concentration at the high temperature flame front. This "prompt" nanoparticle generation is consistent with kinetic models describing iron cluster formation. The observation of this phenomenon in a quasi-one-dimensional premixed flat flame strengthens our previous findings and points out that the "prompt" nanoparticle formation is a general phenomenon, not limited to diffusion flames. It presents a challenge and a trigger for further development of the existing mechanisms for gas phase synthesis of iron oxide particles in flames. This journal is © the Owner Societies 2015.
    view abstractdoi: 10.1039/c4cp04454a
  • 2015 • 370 Influence of humidity on the phase behavior of API/polymer formulations
    Prudic, A. and Ji, Y. and Luebbert, C. and Sadowski, G.
    European Journal of Pharmaceutics and Biopharmaceutics 94 352-362 (2015)
    Amorphous formulations of APIs in polymers tend to absorb water from the atmosphere. This absorption of water can induce API recrystallization, leading to reduced long-term stability during storage. In this work, the phase behavior of different formulations was investigated as a function of relative humidity. Indomethacin and naproxen were chosen as model APIs and poly(vinyl pyrrolidone) (PVP) and poly(vinyl pyrrolidone-co-vinyl acetate) (PVPVA64) as excipients. The formulations were prepared by spray drying. The water sorption in pure polymers and in formulations was measured at 25 °C and at different values of relative humidity (RH = 25%, 50% and 75%). Most water was absorbed in PVP-containing systems, and water sorption was decreasing with increasing API content. These trends could also be predicted in good agreement with the experimental data using the thermodynamic model PC-SAFT. Furthermore, the effect of absorbed water on API solubility in the polymer and on the glass-transition temperature of the formulations was predicted with PC-SAFT and the Gordon-Taylor equation, respectively. The absorbed water was found to significantly decrease the API solubility in the polymer as well as the glass-transition temperature of the formulation. Based on a quantitative modeling of the API/polymer phase diagrams as a function of relative humidity, appropriate API/polymer compositions can now be selected to ensure long-term stable amorphous formulations at given storage conditions. © 2015 Published by Elsevier B.V.
    view abstractdoi: 10.1016/j.ejpb.2015.06.009
  • 2015 • 369 Thermodynamic phase behaviour of indomethacin/PLGA formulations
    Prudic, A. and Lesniak, A.-K. and Ji, Y. and Sadowski, G.
    European Journal of Pharmaceutics and Biopharmaceutics 93 88-94 (2015)
    In the current study, the phase behaviour of indomethacin and poly(lactic-co-glycolic acid) (PLGA) formulations was investigated as a function of the molecular weight and the copolymer composition of PLGA. The formulations were prepared by ball milling, and the phase behaviour, comprised of the glass-transition temperature of the formulations and the solubility of indomethacin in PLGA, was measured using modulated differential scanning calorimetry (mDSC). The results determined that the solubility of indomethacin in PLGA at room temperature was very low and increased with a corresponding decrease in the molecular weight of PLGA. The copolymer composition of PLGA had a minor effect on the indomethacin solubility. The effect of PLGA's molecular weight and copolymer composition on the solubility of indomethacin could be modelled using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) with a high degree of accuracy when compared with the experimental data. The glass-transition temperatures had a negative deviation from the weighted mean of the glass-transition temperatures of the pure substances, which could be described by the Kwei-equation. © 2015 Published by Elsevier B.V.
    view abstractdoi: 10.1016/j.ejpb.2015.01.029
  • 2015 • 368 A short, rigid linker between pyrene and guanidiniocarbonyl-pyrrole induced a new set of spectroscopic responses to the ds-DNA secondary structure
    Radić Stojković, M. and Piotrowski, P. and Schmuck, C. and Piantanida, I.
    Organic and Biomolecular Chemistry 13 1629-1633 (2015)
    A novel pyrene-guanidiniocarbonyl-pyrrole dye, characterised by a short, rigid linker between the two chromophores, interacts strongly with ds-DNA but only negligibly with ds-RNA. Under neutral conditions the dye shows strong selectivity toward AT-DNA (with respect to GC-DNA). Binding is accompanied by a specific ICD band at 350 nm and fluorescence quenching for all DNAs/RNAs studied. At pH 5 the affinity of the dye is reversed, now favouring GC-DNA over AT-DNA. A strong emission increase for AT-DNA is observed but with quenching for GC-DNA. © The Royal Society of Chemistry 2015.
    view abstractdoi: 10.1039/c4ob02169j
  • 2015 • 367 Chemical cross-linking of polypropylenes towards new shape memory polymers
    Raidt, T. and Hoeher, R. and Katzenberg, F. and Tiller, J.C.
    Macromolecular Rapid Communications 36 744-749 (2015)
    In this work, syndiotactic polypropylene (sPP) as well as isotactic polypropylene (iPP) are cross-linked to gain a shape memory effect. Both prepared PP networks exhibit maximum strains of 700%, stored strains of up to 680%, and recoveries of nearly 100%. While x-iPP is stable for many cycles, x-sPP ruptures after the first shape-memory cycle. It is shown by wide-angle X-ray scattering (WAXS) experiments that cross-linked iPP exhibits homoepitaxy in the temporary, stretched shape but in contrast to previous reports it contains a higher amount of daughter than mother crystals. Shape memory polypropylene is prepared by cross-linking of syndiotactic as well as isotactic polypropylene (iPP). Cross-linked iPP is a shape-memory polymer with excellent stored strain, fixity-, and recovery-ratios. Wide angle X-ray scattering (WAXS) experiments reveal that the crystals in programmed x-iPP show a microstructure with mother and daughter crystals. In contrast to previous reports, the amount of daughter crystals exceeds that of the mothers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/marc.201400727
  • 2015 • 366 Post-polymerization of urease-induced calcified, polymer hydrogels
    Rauner, N. and Buenger, L. and Schuller, S. and Tiller, J.C.
    Macromolecular Rapid Communications 36 224-230 (2015)
    Urease-induced calcification is an innovative method to artificially produce highly filled CaCO3-based composite materials by intrinsic mineralization of hydrogels. The mechanical properties of these hybrid materials based on poly(2-hydroxyethylacrylate) cross-linked by triethylene glycol dimethacrylate are poor. Increasing the degree of calcification to up to 94 wt% improves the Young's moduli (YM) of the materials from some 40 MPa to more than 300 MPa. The introduction of calcium carbonate affine groups to the hydrogel matrix by copolymerizing acrylic acid and [2-(methacryloyloxy) ethyl]trimethylammonium chloride, respectively, does not increase the stiffness of the composites. A Young's modulus of more than 1 GPa is achieved by post-polymerization (PP) of the calcified hydrogels, which proves that the size of the contact area between the matrix and calcium carbonate crystals is the most crucial parameter for controlling the stiffness of hybrid materials. Switching from low Tg to high Tg hydrogel matrices (based on poly(N,N-dimethyl acrylamide)) results in a YM of up to 3.5 GPa after PP. (Chemical Equation Presented). © 2014 Wiley-VCH Verlag GmbH & Co. KGaA.
    view abstractdoi: 10.1002/marc.201400426
  • 2015 • 365 Identification and further development of potent TBK1 inhibitors
    Richters, A. and Basu, D. and Engel, J. and Ercanoglu, M.S. and Balke-Want, H. and Tesch, R. and Thomas, R.K. and Rauh, D.
    ACS Chemical Biology 10 289-298 (2015)
    The cytosolic Ser/Thr kinase TBK1 was discovered to be an essential element in the mediation of signals that lead to tumor migration and progression. These findings meet the need for the identification of novel tool compounds and potential therapeutics to gain deeper insights into TBK1 related signaling and its relevance in tumor progression. Herein, we undertake the activity-based screening for unique inhibitors of TBK1 and their subsequent optimization. Initial screening approaches identified a selection of TBK1 inhibitors that were optimized using methods of medicinal chemistry. Variations of the structural characteristics of a representative 2,4,6-substituted pyrimidine scaffold resulted in improved potency. Prospective use as tool compounds or basic contributions to drug design approaches are anticipated for our improved small molecules. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/cb500908d
  • 2015 • 364 Using cavity microelectrodes for electrochemical noise studies of oxygen-evolving catalysts
    Rincón, R.A. and Battistel, A. and Ventosa, E. and Chen, X. and Nebel, M. and Schuhmann, W.
    ChemSusChem 8 560-566 (2015)
    Cavity microelectrodes were used as a binder-free platform to evaluate oxygen evolution reaction (OER) electrocatalysts with respect to gas bubble formation and departure. Electrochemical noise measurements were performed by using RuO2 as a benchmark catalyst and the perovskite La0.58Sr0.4Fe0.8Co0.2O3 as a non-noble metal OER catalyst with lower intrinsic conductivity. Changes in the current during the OER originate from variations in electrolyte resistance during the formation of the gas phase and partial coverage of the active area. Fluctuations observed in current and conductance transients were used to establish the contribution from the ohmic overpotential and to determine the characteristic frequency of oxygen evolution. The proposed quantitative determination of gas bubble growth and departure opens up the route for a rational interface design by considering gas bubble growth and departure as a main contributing factor to the overall electrocatalytic activity at high current densities. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.201402855
  • 2015 • 363 Reversible reconfiguration of DNA origami nanochambers monitored by single-molecule FRET
    Saccà, B. and Ishitsuka, Y. and Meyer, R. and Sprengel, A. and Schöneweiß, E.-C. and Nienhaus, G.U. and Niemeyer, C.M.
    Angewandte Chemie - International Edition 54 3592-3597 (2015)
    Today, DNA nanotechnology is one of the methods of choice to achieve spatiotemporal control of matter at the nanoscale. By combining the peculiar spatial addressability of DNA origami structures with the switchable mechanical movement of small DNA motifs, we constructed reconfigurable DNA nanochambers as dynamic compartmentalization systems. The reversible extension and contraction of the inner cavity of the structures was used to control the distance-dependent energy transfer between two preloaded fluorophores. Interestingly, single-molecule FRET studies revealed that the kinetics of the process are strongly affected by the choice of the switchable motifs and/or actuator sequences, thus offering a valid method for fine-tuning the dynamic properties of large DNA nanostructures. We envisage that the proposed DNA nanochambers may function as model structures for artificial biomimetic compartments and transport systems. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201408941
  • 2015 • 362 Solvent free production of porous PDLLA/calcium carbonate composite scaffolds improves the release of bone growth factors
    Schliephake, H. and Vucak, M. and Boven, J. and Backhaus, S. and Annen, T. and Epple, M.
    Oral and Maxillofacial Surgery 19 133-141 (2015)
    Purpose: Incorporation of alkaline nano-/microparticles for neutralization of acidic degradation products into degradable polymer foams requires the use of organic solvents, which may compromise biocompatibility and may be associated with biological hazards. The aim of the present study was to develop and validate a solvent-free method to produce porous poly (DL-lactic acid)/calcium carbonate composite scaffolds (PDLLA/CaCO<inf>3</inf>) for controlled release of incorporated osteogenic growth factors. Methods: Composite PDLLA/CaCO<inf>3</inf> granules were produced using a milling process and compared to composite material fabricated through a solution precipitation process using organic solvents. Particle size and mineral content were comparable in both groups. Supercritical carbon dioxide pressure was used to incorporate rhBMP2 into both composites. Results: Gas foaming resulted in comparable pore structures in both groups exhibiting a homogenous distribution of CaCO<inf>3</inf> microparticles in the polymer scaffolds. The elasticity modulus of both types of scaffolds was not significantly different whereas the bending strength of the solvent-free produced scaffolds was significantly lower. The pH values remained constant between 6.90 and 7.25 during degradation of both composites. Release of BMP2 was significantly higher and the induction of alkaline phosphatase was more reliable in the group of scaffolds produced without organic solvents. Conclusion: Solvent-free fabrication of composite PDLLA/CaCO<inf>3</inf> scaffolds for controlled release of bone growth factors through gas foaming significantly enhances the release of growth factors and improves the biological efficacy of the incorporated growth factors. © 2014, Springer-Verlag Berlin Heidelberg.
    view abstractdoi: 10.1007/s10006-014-0463-4
  • 2015 • 361 Conjugation of ciprofloxacin with poly(2-oxazoline)s and polyethylene glycol via end groups
    Schmidt, M. and Harmuth, S. and Barth, E.R. and Wurm, E. and Fobbe, R. and Sickmann, A. and Krumm, C. and Tiller, J.C.
    Bioconjugate Chemistry 26 1950-1962 (2015)
    The antibiotic ciprofloxacin (CIP) was covalently attached to the chain end of poly(2-methyloxazoline) (PMOx), poly(2-ethyloxazoline) (PEtOx), and polyethylene glycol (PEG), and the antimicrobial activity of these conjugates was tested for Staphylococcus aureus, Streptococcus mutans, Escherichia coli, Pseudomonas aeruginosa, and Kleisella pneumoniae. Chemical structures of the conjugates were proven by 1H NMR and electron spray ionization mass spectrometry. The direct coupling of PMOx and CIP resulted in low antimicrobial activity. The coupling via a spacer afforded molecular weight dependent activity with a molar minimal inhibitory concentration that is even higher than that of the pristine CIP. The antimicrobial activity of the conjugates increases in the order of PMOx < PEtOx < PEG. Conjugation of CIP and a quaternary ammonium compound via PMOx did not result in higher activity, indicating no satellite group or synergistic effect of the different biocidal end groups. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/acs.bioconjchem.5b00393
  • 2015 • 360 Selective enzymatic removal of elastin and collagen from human abdominal aortas: Uniaxial mechanical response and constitutive modeling
    Schriefl, A.J. and Schmidt, T. and Balzani, D. and Sommer, G. and Holzapfel, G.A.
    Acta Biomaterialia 17 125-136 (2015)
    The ability to selectively remove the structurally most relevant components of arterial wall tissues such as collagen and elastin enables ex vivo biomechanical testing of the remaining tissues, with the aim of assessing their individual mechanical contributions. Resulting passive material parameters can be utilized in mathematical models of the cardiovascular system. Using eighteen wall specimens fromnon-atherosclerotic human abdominal aortas (55±11 years; 9 female, 9 male), we tested enzymatic approaches for the selective digestion of collagen and elastin, focusing on their application to human abdominal aortic wall tissues from different patients with varying sample morphologies. The study resulted in an improved protocol for elastin removal, showing how the enzymatic process is affected by inadequate addition of trypsin inhibitor. We applied the resulting protocol to circumferential and axial specimens from the media and the adventitia, and performed cyclic uniaxial extension tests in the physiological and supra-physiological loading domain. The collagenase-treated samples showed a (linear) response without distinct softening behavior, while the elastase-treated samples exhibited a nonlinear, anisotropic response with pronounced remanent deformations (continuous softening), presumably caused by some sliding of collagen fibers within the damaged regions of the collagen network. In addition, our data showed that the stiffness in the initial linear stress-stretch regime at low loads is lower in elastin-free tissue compared to control samples (i.e. collagen uncrimping requires less force than the stretching of elastin), experimentally confirming that elastin is responsible for the initial stiffness in elastic arteries. Utilizing a continuum mechanical description to mathematically capture the experimental results we concluded that the inclusion of a damage model for the non-collagenous matrix material is, in general, not necessary. To model the softening behavior, continuous damage was included in the fibers by adding a damage variable which led to remanent strains through the consideration of damage. © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
    view abstractdoi: 10.1016/j.actbio.2015.01.003
  • 2015 • 359 Neuritogenic Militarinone-Inspired 4-Hydroxypyridones Target the Stress Pathway Kinase MAP4K4
    Schröder, P. and Förster, T. and Kleine, S. and Becker, C. and Richters, A. and Ziegler, S. and Rauh, D. and Kumar, K. and Waldmann, H.
    Angewandte Chemie - International Edition 54 12398-12403 (2015)
    Progressive loss and impaired restoration of neuronal activity are hallmarks of neurological diseases, and new small molecules with neurotrophic activity are in high demand. The militarinone alkaloids and structurally simplified analogues with 4-hydroxy-2-pyridone core structure induce pronounced neurite outgrowth, but their protein target has not been identified. Reported herein is the synthesis of a militarinone-inspired 4-hydroxy-2-pyridone collection, its investigation for enhancement of neurite outgrowth, and the discovery of the stress pathway kinase MAP4K4 as a target of the discovered neuritogenic pyridones. The most potent 4-hydroxy-2-pyridone is a selective ATP-competitive inhibitor of MAP4K4 but not of the other stress pathway related kinases, as proven by biochemical analysis and by a crystal structure of the inhibitor in complex with MAP4K4. The findings support the notion that MAP4K4 may be a new target for the treatment of neurodegenerative diseases. No stress: Reported herein is the synthesis of a militarinone-inspired 4-hydroxy-2-pyridone collection, its investigation for enhancement of neurite outgrowth, and the discovery of the stress pathway kinase MAP4K4 as a target of the discovered neuritogenic pyridones. The findings support the notion that MAP4K4 may be a new target for the treatment of neurodegenerative diseases. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201501515
  • 2015 • 358 Electrochemical detection of single E. coli bacteria labeled with silver nanoparticles
    Sepunaru, L. and Tschulik, K. and Batchelor-McAuley, C. and Gavish, R. and Compton, R.G.
    Biomaterials Science 3 816-820 (2015)
    A proof-of-concept for the electrochemical detection of single Escherichia coli bacteria decorated with silver nanoparticles is reported. Impacts of bacteria with an electrode - held at a suitably oxidizing potential - lead to an accompanying burst of current with each collision event. The frequency of impacts scales with the concentration of bacteria and the charge indicates the extent of decoration. © The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c5bm00114e
  • 2015 • 357 High-Throughput Screening of Thin-Film Semiconductor Material Libraries I: System Development and Case Study for Ti-W-O
    Sliozberg, K. and Schäfer, D. and Erichsen, T. and Meyer, R. and Khare, C. and Ludwig, Al. and Schuhmann, W.
    ChemSusChem 8 1270-1278 (2015)
    An automated optical scanning droplet cell (OSDC) enables high-throughput quantitative characterization of thin-film semiconductor material libraries. Photoelectrochemical data on small selected measurement areas are recorded including intensity-dependent photopotentials and -currents, potentiodynamic and potentiostatic photocurrents, as well as photocurrent (action) spectra. The OSDC contains integrated counter and double-junction reference electrodes and is fixed on a precise positioning system. A Xe lamp with a monochromator is coupled to the cell through a thin poly(methyl methacrylate) (PMMA) optical fiber. A specifically designed polytetrafluoroethylene (PTFE) capillary tip is pressed on the sample surface and defines through its diameter the homogeneously illuminated measurement area. The overall and wavelength-resolved irradiation intensities and the cell surface area are precisely determined and calibrated. System development and its performance are demonstrated by means of screening of a Ti-W-O thin film. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA.
    view abstractdoi: 10.1002/cssc.201402917
  • 2015 • 356 Reversible or Not? Distinguishing Agglomeration and Aggregation at the Nanoscale
    Sokolov, S.V. and Tschulik, K. and Batchelor-McAuley, C. and Jurkschat, K. and Compton, R.G.
    Analytical Chemistry 87 10033-10039 (2015)
    Nanoparticles are prone to clustering either via aggregation (irreversible) or agglomeration (reversible) processes. It is exceedingly difficult to distinguish the two via conventional techniques such as dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), or electron microscopy imaging (scanning electron microscopy (SEM), transmission electron microscopy (TEM)) as such techniques only generally confirm the presence of large particle clusters. Herein we develop a joint approach to tackle the issue of distinguishing between nanoparticle aggregation vs agglomeration by characterizing a colloidal system of Ag NPs using DLS, NTA, SEM imaging and the electrochemical nanoimpacts technique. In contrast to the conventional techniques which all reveal the presence of large clusters of particles, electrochemical nanoimpacts provide information regarding individual nanoparticles in the solution phase and reveal the presence of small nanoparticles (<30 nm) even in high ionic strength (above 0.5 M KCl) and allow a more complete analysis. The detection of small nanoparticles in high ionic strength media evidence the clustering to be a reversible process. As a result it is concluded that agglomeration rather than irreversible aggregation takes place. This observation is of general importance for all colloids as it provides a feasible analysis technique for a wide range of systems with an ability to distinguish subtly different processes. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/acs.analchem.5b02639
  • 2015 • 355 Why phosphoproteomics is still a challenge
    Solari, F.A. and Dell'Aica, M. and Sickmann, A. and Zahedi, R.P.
    Molecular BioSystems 11 1487-1493 (2015)
    Despite continuous improvements phosphoproteomics still faces challenges that are often neglected, e.g. partially poor recovery of phosphopeptide enrichment, assessment of phosphorylation stoichiometry, label-free quantification, poor behavior during chromatography, and general limitations of peptide-centric proteomics. Here we critically discuss current limitations that need consideration in both qualitative and quantitative studies. © The Royal Society of Chemistry 2015.
    view abstractdoi: 10.1039/c5mb00024f
  • 2015 • 354 Nontoxic, Hydrophilic Cationic Polymers - Identified as Class of Antimicrobial Polymers
    Strassburg, A. and Kracke, F. and Wenners, J. and Jemeljanova, A. and Kuepper, J. and Petersen, H. and Tiller, J.C.
    Macromolecular Bioscience 15 1710-1723 (2015)
    Amphiphilic polycations are an alternative to biocides but also toxic to mammalian cells. Antimicrobially active hydrophilic polycations based on 1,4-dibromo-2-butene and tetramethyl-1,3-propanediamine named PBI are not hemotoxic for porcine red blood cells with a hemocytotoxicity (HC50) of more than 40 000 μg · mL-1. They are quickly killing bacterial cells at their MIC (minimal inhibitory concentration). The highest found selectivity HC50/MIC is more than 20 000 for S. epidermidis. Investigations on sequentially prepared PBIs with defined molecular weight Mn and tailored end groups revealed that there is a dependence of antimicrobial activity and selectivity on Mn and nature of the end groups. Antimicrobially active and nontoxic hydrophilic polycations based on 1,4-dibromo-2-butene and tetramethyl-1,3-propanediamine (PBI) are an alternative to toxic biocides and amphiphilic polycations. Investigations on PBIs with defined molecular weight (Mn) and tailored end groups revealed that there is a dependence of antimicrobial activity and selectivity on Mn and nature of the end groups. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/mabi.201500207
  • 2015 • 353 Non-destructive Patterning of Carbon Electrodes by Using the Direct Mode of Scanning Electrochemical Microscopy
    Stratmann, L. and Clausmeyer, J. and Schuhmann, W.
    ChemPhysChem 16 3477-3482 (2015)
    Patterning of glassy carbon surfaces grafted with a layer of nitrophenyl moieties was achieved by using the direct mode of scanning electrochemical microscopy (SECM) to locally reduce the nitro groups to hydroxylamine and amino functionalities. SECM and atomic force microscopy (AFM) revealed that potentiostatic pulses applied to the working electrode lead to local destruction of the glassy carbon surface, most likely caused by etchants generated at the positioned SECM tip used as the counter electrode. By applying galvanostatic pulses, and thus, limiting the current during structuring, corrosion of the carbon surface was substantially suppressed. After galvanostatic patterning, unambiguous proof of the formation of the anticipated amino moieties was possible by modulation of the pH value during the feedback mode of SECM imaging. This patterning strategy is suitable for the further bio-modification of microstructured surfaces. Alkaline phosphatase, as a model enzyme, was locally bound to the modified areas, thus showing that the technique can be used for the development of protein microarrays. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cphc.201500585
  • 2015 • 352 Effects of various chair-side surface treatment methods on dental restorative materials with respect to contact angles and surface roughness
    Sturz, C.R.C. and Faber, F.-J. and Scheer, M. and Rothamel, D. and Neugebauer, J.
    Dental Materials Journal 34 796-813 (2015)
    Available chair-side surface treatment methods may adversely affect prosthetic materials and promote plaque accumulation. This study investigated the effects of treatment procedures on three resin restorative materials, zirconium-dioxide and polyetheretherketone in terms of surface roughness and hydrophobicity. Treatments were grinding with silicon carbide paper or white Arkansas stone, blasting with prophylaxis powder and polishing with diamond paste. Surface roughness was assessed using confocal laser scanning. Hydrophobicity as measured by water contact angle was determined by computerized image analysis using the sessile drop technique. All of the specific surface treatments performed led to significant changes in contact angle values and surface roughness (Ra) values. Median contact angle values ranged from 51.6° to 114°. Ra values ranged from 0.008 μm to 2.917 μm. Air-polishing as well as other polishing procedures increased surface roughness values in all materials except zirconium dioxide. Polyetheretherketone displayed greatest change in contact angle values after air-polishing treatment. © 2015, Japanese Society for Dental Materials and Devices. All rights reserved.
    view abstractdoi: 10.4012/dmj.2014-098
  • 2015 • 351 Mechanical Properties of a Calcium Dietary Supplement, Calcium Fumarate Trihydrate
    Sun, S. and Henke, S. and Wharmby, M.T. and Yeung, H.H.-M. and Li, W. and Cheetham, A.K.
    Inorganic Chemistry 54 11186-11192 (2015)
    The mechanical properties of calcium fumarate trihydrate, a 1D coordination polymer considered for use as a calcium source for food and beverage enrichment, have been determined via nanoindentation and high-pressure X-ray diffraction with single crystals. The nanoindentation studies reveal that the elastic modulus (16.7-33.4 GPa, depending on crystallographic orientation), hardness (1.05-1.36 GPa), yield stress (0.70-0.90 GPa), and creep behavior (0.8-5.8 nm/s) can be rationalized in view of the anisotropic crystal structure; factors include the directionality of the inorganic Ca-O-Ca chain and hydrogen bonding, as well as the orientation of the fumarate ligands. High-pressure single-crystal X-ray diffraction studies show a bulk modulus of ∼20 GPa, which is indicative of elastic recovery intermediate between small molecule drug crystals and inorganic pharmaceutical ingredients. The combined use of nanoindentation and high-pressure X-ray diffraction techniques provides a complementary experimental approach for probing the critical mechanical properties related to tableting of these dietary supplements. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/acs.inorgchem.5b01466
  • 2015 • 350 Nano-hydroxyapatite-coated metal-ceramic composite of iron-tricalcium phosphate: Improving the surface wettability, adhesion and proliferation of mesenchymal stem cells in vitro
    Surmeneva, M.A. and Kleinhans, C. and Vacun, G. and Kluger, P.J. and Schönhaar, V. and Müller, M. and Hein, S.B. and Wittmar, A. and Ulbricht, M. and Prymak, O. and Oehr, C. and Surmenev, R.A.
    Colloids and Surfaces B: Biointerfaces 135 386-393 (2015)
    Thin radio-frequency magnetron sputter deposited nano-hydroxyapatite (HA) films were prepared on the surface of a Fe-tricalcium phosphate (Fe-TCP) bioceramic composite, which was obtained using a conventional powder injection moulding technique. The obtained nano-hydroxyapatite coated Fe-TCP biocomposites (nano-HA-Fe-TCP) were studied with respect to their chemical and phase composition, surface morphology, water contact angle, surface free energy and hysteresis. The deposition process resulted in a homogeneous, single-phase HA coating. The ability of the surface to support adhesion and the proliferation of human mesenchymal stem cells (hMSCs) was studied using biological short-term tests in vitro. The surface of the uncoated Fe-TCP bioceramic composite showed an initial cell attachment after 24 h of seeding, but adhesion, proliferation and growth did not persist during 14 days of culture. However, the HA-Fe-TCP surfaces allowed cell adhesion, and proliferation during 14 days. The deposition of the nano-HA films on the Fe-TCP surface resulted in higher surface energy, improved hydrophilicity and biocompatibility compared with the surface of the uncoated Fe-TCP. Furthermore, it is suggested that an increase in the polar component of the surface energy was responsible for the enhanced cell adhesion and proliferation in the case of the nano-HA-Fe-TCP biocomposites. © 2015 Elsevier B.V.
    view abstractdoi: 10.1016/j.colsurfb.2015.07.057
  • 2015 • 349 Doping Level of Boron-Doped Diamond Electrodes Controls the Grafting Density of Functional Groups for DNA Assays
    Švorc, L. and Jambrec, D. and Vojs, M. and Barwe, S. and Clausmeyer, J. and Michniak, P. and Marton, M. and Schuhmann, W.
    ACS Applied Materials and Interfaces 7 18949-18956 (2015)
    The impact of different doping levels of boron-doped diamond on the surface functionalization was investigated by means of electrochemical reduction of aryldiazonium salts. The grafting efficiency of 4-nitrophenyl groups increased with the boron levels (B/C ratio from 0 to 20 000 ppm). Controlled grafting of nitrophenyldiazonium was used to adjust the amount of immobilized single-stranded DNA strands at the surface and further on the hybridization yield in dependence on the boron doping level. The grafted nitro functions were electrochemically reduced to the amine moieties. Subsequent functionalization with a succinic acid introduced carboxyl groups for subsequent binding of an amino-terminated DNA probe. DNA hybridization significantly depends on the probe density which is in turn dependent on the boron doping level. The proposed approach opens new insights for the design and control of doped diamond surface functionalization for the construction of DNA hybridization assays. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/acsami.5b06394
  • 2015 • 348 Mechanistic study of carvacrol processing and stabilization as glassy solid solution and microcapsule
    Tackenberg, M.W. and Geisthövel, C. and Marmann, A. and Schuchmann, H.P. and Kleinebudde, P. and Thommes, M.
    International Journal of Pharmaceutics 478 530-539 (2015)
    Essential oils and other liquid active pharmaceutical ingredients (APIs) are frequently microencapsulated to improve shelf life, handling, and for tailoring release. A glassy solid solution (GSS), a single-phase system, where the excipient is plasticized by the API, could be an alternative formulation system. Thus this study focuses on the investigation of two formulation strategies using carvacrol as a model compound, namely a microcapsule (MC) and a glassy solid solution (GSS). Applying the solubility parameter approach, polyvinylpyrrolidone (PVP) was chosen as a suitable matrix material for a GSS system, whereas maltodextrin and sucrose served as excipients for a microcapsule (MC) system. Differential scanning calorimetry (DSC) measurements of the excipients' glass transition temperatures and the melting point of carvacrol verified plasticizing properties of carvacrol on PVP. Batch mixing processes, as preliminary experiments for future extrusion processes, were performed to prepare GSSs and MCs with various amounts of carvacrol, followed by crushing and sieving. Maximally 4.5% carvacrol was encapsulated in the carbohydrate material, whereas up to 16.3% were stabilized as GSS, which is an outstanding amount. However, grinding of the samples led to a loss of up to 30% of carvacrol. © 2014 Published by Elsevier B.V.
    view abstractdoi: 10.1016/j.ijpharm.2014.12.012
  • 2015 • 347 Encapsulation of liquids using a counter rotating twin screw extruder
    Tackenberg, M.W. and Krauss, R. and Marmann, A. and Thommes, M. and Schuchmann, H.P. and Kleinebudde, P.
    European Journal of Pharmaceutics and Biopharmaceutics 89 9-17 (2015)
    Until now extrusion is not applied for pharmaceutical encapsulation processes, whereas extrusion is widely used for encapsulation of flavours within food applications. Based on previous mixing studies, a hot melt counter-rotating extrusion process for encapsulation of liquid active pharmaceutical ingredients (APIs) was investigated. The mixing ratio of maltodextrin to sucrose as matrix material was adapted in first extrusion trials. Then the number of die holes was investigated to decrease expansion and agglutination of extrudates to a minimum. At a screw speed of 180 min-1 the product temperature was decreased below 142°C, resulting in extrudates of cylindrical shape with a crystalline content of 9-16%. Volatile orange terpenes and the nonvolatile α-tocopherol were chosen as model APIs. Design of experiments were performed to investigate the influences of barrel temperature, powder feed rate, and API content on the API retentions. A maximum of 9.2% α-tocopherol was encapsulated, while the orange terpene encapsulation rate decreased to 6.0% due to evaporation after leaving the die. During 12 weeks of storage re-crystallization of sucrose occurred; however, the encapsulated orange terpene amount remained unchanged. © 2014 Elsevier B.V. All rights reserved.
    view abstractdoi: 10.1016/j.ejpb.2014.11.017
  • 2015 • 346 Combining X-ray crystallography and molecular modeling toward the optimization of pyrazolo[3,4-d ]pyrimidines as potent c-Src inhibitors active in vivo against neuroblastoma
    Tintori, C. and Fallacara, A.L. and Radi, M. and Zamperini, C. and Dreassi, E. and Crespan, E. and Maga, G. and Schenone, S. and Musumeci, F. and Brullo, C. and Richters, A. and Gasparrini, F. and Angelucci, A. and Festuccia, C. a...
    Journal of Medicinal Chemistry 58 347-361 (2015)
    c-Src is a tyrosine kinase belonging to the Src-family kinases. It is overexpressed and/or hyperactivated in a variety of cancer cells, thus its inhibition has been predicted to have therapeutic effects in solid tumors. Recently, the pyrazolo[3,4-d]pyrimidine 3 was reported as a dual c-Src/Abl inhibitor. Herein we describe a multidisciplinary drug discovery approach for the optimization of the lead 3 against c-Src. Starting from the X-ray crystal structure of c-Src in complex with 3, Monte Carlo free energy perturbation calculations were applied to guide the design of c-Src inhibitors with improved activities. As a result, the introduction of a meta hydroxyl group on the C4 anilino ring was computed to be particularly favorable. The potency of the synthesized inhibitors was increased with respect to the starting lead 3. The best identified compounds were also found active in the inhibition of neuroblastoma cell proliferation. Furthermore, compound 29 also showed in vivo activity in xenograft model using SH-SY5Y cells. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/jm5013159
  • 2015 • 345 Mesoscopic simulation of phospholipid membranes, peptides, and proteins with molecular fragment dynamics
    Truszkowski, A. and Van Den Broek, K. and Kuhn, H. and Zielesny, A. and Epple, M.
    Journal of Chemical Information and Modeling 55 983-997 (2015)
    Molecular fragment dynamics (MFD) is a variant of dissipative particle dynamics (DPD), a coarse-grained mesoscopic simulation technique for isothermal complex fuids and soft matter systems with particles that are chosen to be adequate fluid elements. MFD choses its particles to be small molecules which may be connected by harmonic springs to represent larger molecular entities in order to maintain a comparatively accurate representation of covalent bonding and molecular characteristics. For this study the MFD approach is extended to accomplish long-term simulations (up to the microsecond scale) of large molecular ensembles (representing millions of atoms) containing phospholipid membranes, peptides, and proteins. For peptides and proteins a generally applicable fragmentation scheme is introduced in combination with specific backbone forces that keep native spatial shapes with adequate levels of flexibility or rigidity. The new approach is demonstrated by MFD simulations of the formation and characteristics of phospholipid membranes and vesicles, vesicle-membrane fusion, the backbone force dependency of the overall structural flexibility of dumbbell-shaped Calmodulin, the stability of subunit-aggregation of tetrameric hemoglobin, and the collaborative interaction of Kalata B1 cyclotides with a phospholipid membrane. All findings are in reasonable agreement with experimental as well as alternative simulation results. Thus, the extended MFD approach may become a new tool for biomolecular system studies to allow for comparatively fast simulative investigations in combination with a comparatively high chemical granularity. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/ci5006096
  • 2015 • 344 Holographic microscopy provides new insights into the settlement of zoospores of the green alga Ulva linza on cationic oligopeptide surfaces
    Vater, S.M. and Finlay, J. and Callow, M.E. and Callow, J.A. and Ederth, T. and Liedberg, B. and Grunze, M. and Rosenhahn, A.
    Biofouling 31 229-239 (2015)
    Interaction of zoospores of Ulva linza with cationic, arginine-rich oligopeptide self-assembled monolayers (SAMs) is characterized by rapid settlement. Some spores settle (ie permanently attach) in a ‘normal’ manner involving the secretion of a permanent adhesive, retraction of the flagella and cell wall formation, whilst others undergo ‘pseudosettlement’ whereby motile spores are trapped (attached) on the SAM surface without undergoing the normal metamorphosis into a settled spore. Holographic microscopy was used to record videos of swimming zoospores in the vicinity of surfaces with different cationic oligopeptide concentrations to provide time-resolved insights into processes associated with attachment of spores. The data reveal that spore attachment rate increases with increasing cationic peptide content. Accordingly, the decrease in swimming activity in the volume of seawater above the surface accelerated with increasing surface charge. Three-dimensional trajectories of individual swimming spores showed a ‘hit and stick’ motion pattern, exclusively observed for the arginine-rich peptide SAMs, whereby spores were immediately trapped upon contact with the surface. © 2015 Taylor & Francis.
    view abstractdoi: 10.1080/08927014.2015.1022534
  • 2015 • 343 PeptideShaker enables reanalysis of MS-derived proteomics data sets: To the editor
    Vaudel, M. and Burkhart, J.M. and Zahedi, R.P. and Oveland, E. and Berven, F.S. and Sickmann, A. and Martens, L. and Barsnes, H.
    Nature Biotechnology 33 22-24 (2015)
    doi: 10.1038/nbt.3109
  • 2015 • 342 Non-aqueous semi-solid flow battery based on Na-ion chemistry. P2-type NaxNi0.22Co0.11Mn0.66O2-NaTi2(PO4)3
    Ventosa, E. and Buchholz, D. and Klink, S. and Flox, C. and Chagas, L.G. and Vaalma, C. and Schuhmann, W. and Passerini, S. and Morante, J.R.
    Chemical Communications 51 7298-7301 (2015)
    We report the first proof of concept for a non-aqueous semi-solid flow battery (SSFB) based on Na-ion chemistry using P2-type Na<inf>x</inf>Ni<inf>0.22</inf>Co<inf>0.11</inf>Mn<inf>0.66</inf>O<inf>2</inf> and NaTi<inf>2</inf>(PO<inf>4</inf>)<inf>3</inf> as positive and negative electrodes, respectively. This concept opens the door for developing a new low-cost type of non-aqueous semi-solid flow batteries based on the rich chemistry of Na-ion intercalating compounds. © The Royal Society of Chemistry 2015.
    view abstractdoi: 10.1039/c4cc09597a
  • 2015 • 341 Effect of the addition of low rare earth elements (lanthanum, neodymium, cerium) on the biodegradation and biocompatibility of magnesium
    Willbold, E. and Gu, X. and Albert, D. and Kalla, K. and Bobe, K. and Brauneis, M. and Janning, C. and Nellesen, J. and Czayka, W. and Tillmann, W. and Zheng, Y. and Witte, F.
    Acta Biomaterialia 11 554-562 (2015)
    Rare earth elements are promising alloying element candidates for magnesium alloys used as biodegradable devices in biomedical applications. Rare earth elements have significant effects on the high temperature strength as well as the creep resistance of alloys and they improve magnesium corrosion resistance. We focused on lanthanum, neodymium and cerium to produce magnesium alloys with commonly used rare earth element concentrations. We showed that low concentrations of rare earth elements do not promote bone growth inside a 750 μm broad area around the implant. However, increased bone growth was observed at a greater distance from the degrading alloys. Clinically and histologically, the alloys and their corrosion products caused no systematic or local cytotoxicological effects. Using microtomography and in vitro experiments, we could show that the magnesium-rare earth element alloys showed low corrosion rates, both in in vitro and in vivo. The lanthanum- and cerium-containing alloys degraded at comparable rates, whereas the neodymium-containing alloy showed the lowest corrosion rates. © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
    view abstractdoi: 10.1016/j.actbio.2014.09.041
  • 2015 • 340 Label-free biosensors based on in situ formed and functionalized microwires in microfluidic devices
    Xing, Y. and Wyss, A. and Esser, N. and Dittrich, P.S.
    Analyst 140 7896-7901 (2015)
    Label-free biosensors based on in situ formed and functionalized TTF-Au wires were developed using an integrated microfluidic system. By applying different modification protocols, TTF-Au wires were successfully used for sensitive label-free detection of catecholamines and human IgG by Raman spectroscopy. © 2015 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c5an01240f
  • 2015 • 339 Light Induced H2 Evolution from a Biophotocathode Based on Photosystem 1 - Pt Nanoparticles Complexes Integrated in Solvated Redox Polymers Films
    Zhao, F. and Conzuelo, F. and Hartmann, V. and Li, H. and Nowaczyk, M.M. and Plumeré, N. and Rögner, M. and Schuhmann, W.
    Journal of Physical Chemistry B 119 13726-13731 (2015)
    We report on a biophotocathode based on photosystem 1 (PS1)-Pt nanoparticle complexes integrated in a redox hydrogel for photoelectrocatalytic H2 evolution at low overpotential. A poly(vinyl)imidazole Os(bispyridine)2Cl polymer serves as conducting matrix to shuttle the electrons from the electrode to the PS1-Pt complexes embedded within the hydrogel. Light induced charge separation at the PS1-Pt complexes results in the generation of photocurrents (4.8 ± 0.4 μA cm-2) when the biophotocathodes are exposed to anaerobic buffer solutions. Under these conditions, the protons are the sole possible electron acceptors, suggesting that the photocurrent generation is associated with H2 evolution. Direct evidence for the latter process is provided by monitoring the H2 production with a Pt microelectrode in scanning electrochemical microscopy configuration over the redox hydrogel film containing the PS1-Pt complexes under illumination. © 2015 American Chemical Society.
    view abstractdoi: 10.1021/acs.jpcb.5b03511
  • 2015 • 338 Amyloid β-Protein Assembly: The Effect of Molecular Tweezers CLR01 and CLR03
    Zheng, X. and Liu, D. and Klärner, F.-G. and Schrader, T. and Bitan, G. and Bowers, M.T.
    Journal of Physical Chemistry B 119 4831-4841 (2015)
    The early oligomerization of amyloid β-protein (Aβ) has been shown to be an important event in the pathology of Alzheimer's disease (AD). Designing small molecule inhibitors targeting Aβ oligomerization is one attractive and promising strategy for AD treatment. Here we used ion mobility spectrometry coupled to mass spectrometry (IMS-MS) to study the different effects of the molecular tweezers CLR01 and CLR03 on Aβ self-assembly. CLR01 was found to bind to Aβ directly and disrupt its early oligomerization. Moreover, CLR01 remodeled the early oligomerization of Aβ42 by compacting the structures of dimers and tetramers and as a consequence eliminated higher-order oligomers. Unexpectedly, the negative-control derivative, CLR03, which lacks the hydrophobic arms of the tweezer structure, was found to facilitate early Aβ oligomerization. Our study provides an example of IMS as a powerful tool to study and better understand the interaction between small molecule modulators and Aβ oligomerization, which is not attainable by other methods, and provides important insights into therapeutic development of molecular tweezers for AD treatment. (Graph Presented). © 2015 American Chemical Society.
    view abstractdoi: 10.1021/acs.jpcb.5b00692
  • 2015 • 337 Electrochemical detection of synthetic DNA and native 16S rRNA fragments on a microarray using a biotinylated intercalator as coupling site for an enzyme label
    Zimdars, A. and Gebala, M. and Hartwich, G. and Neugebauer, S. and Schuhmann, W.
    Talanta 143 19-26 (2015)
    Abstract The direct electrochemical detection of synthetic DNA and native 16S rRNA fragments isolated from Escherichia coli is described. Oligonucleotides are detected via selective post-labeling of double stranded DNA and DNA-RNA duplexes with a biotinylated intercalator that enables high-specific binding of a streptavidin/alkaline phosphatase conjugate. The alkaline phosphatase catalyzes formation of p-aminophenol that is subsequently oxidized at the underlying gold electrode and hence enables the detection of complementary hybridization of the DNA capture strands due to the enzymatic signal amplification. The hybridization assay was performed on microarrays consisting of 32 individually addressable gold microelectrodes. Synthetic DNA strands with sequences representing six different pathogens which are important for the diagnosis of urinary tract infections could be detected at concentrations of 60 nM. Native 16S rRNA isolated from the different pathogens could be detected at a concentration of 30 fM. Optimization of the sensing surface is described and influences on the assay performance are discussed. © 2015 Elsevier B.V.
    view abstractdoi: 10.1016/j.talanta.2015.04.041
  • 2015 • 336 Peptide self-assembly triggered by metal ions
    Zou, R. and Wang, Q. and Wu, J. and Wu, J. and Schmuck, C. and Tian, H.
    Chemical Society Reviews 44 5200-5219 (2015)
    Through their unique and specific interactions with various metal ions, naturally occurring proteins control structures and functions of many biological processes and functions in organisms. Inspired by natural metallopeptides, chemists have developed artificial peptides which coordinate with metal ions through their functional groups either for introducing a special reactivity or for constructing nanostructures. However, the design of new coordination peptides requires a deep understanding of the structures, assembly properties, and dynamic behaviours of such peptides. This review briefly discusses strategies of peptide self-assembly induced by metal coordination to different natural and non-natural binding sites in the peptide. The structures and functions of the obtained aggregates are described as well. We also highlight some examples of a metal-induced peptide self-assembly with relevance to biotechnology applications. © The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c5cs00234f
  • 2014 • 335 Comparison of silver nanoparticles stored under air or argon with respect to the induction of intracellular free radicals and toxic effects toward keratinocytes
    Ahlberg, S. and Meinke, M.C. and Werner, L. and Epple, M. and Diendorf, J. and Blume-Peytavi, U. and Lademann, J. and Vogt, A. and Rancan, F.
    European Journal of Pharmaceutics and Biopharmaceutics 88 651-657 (2014)
    Bacterial infections decreased considerably after the discovery of antibiotics. Nevertheless, because of the rising rate of infections caused by antibiotic-resistant bacteria strains, the search for new bactericidal agents has again become a crucial topic in clinical medicine. Silver nanoparticles (AgNP) have a huge potential in dermatology and wound care management because of their ability to release silver ions (Ag+ ions) in a prolonged and sustained way. However, negative effects of silver on the patient's cells should not be underestimated. Furthermore, it has been controversially discussed whether AgNP are responsible for nanoparticle-specific outcomes or not. In this study, we investigated the effects of AgNP on human skin keratinocytes (HaCaT) in order to better understand the mechanisms of cytotoxicity and to improve the use of this highly reactive biocide in wound healing. We found that most of the cells with internalized AgNP displayed the typical morphological signs of apoptosis. The cell viability assay (XTT) showed concentration-dependent toxic effects of the AgNP toward HaCaT cells. The generation of reactive oxygen species (ROS) induced by AgNP was investigated in cell suspensions by means of electron paramagnetic resonance (EPR) spectroscopy. In order to distinguish between the effects of Ag+ ions released during AgNP storage and those of Ag+ ions released after nanoparticle application, we compared AgNP stored under air (O2) with AgNP stored under argon (Ar). Dispersions of AgNP stored under Ar have a low content of Ag+ ions because of the absence of oxygen which is needed for oxidative dissolution. The results show that Ag+ ions released during particle storage are responsible for most of the ROS produced during 1 h incubation with the cells. AgNP (Ar) also induced intracellular ROS but to a much smaller extent compared to AgNP (O2). These findings highlight the complexity of experiments to assess the toxicity of AgNP and suggest the possibility of reducing AgNP toxic effects by storing AgNP formulations and even silver-containing wound dressing under an inert gas atmosphere. © 2014 Elsevier B.V. All rights reserved.
    view abstractdoi: 10.1016/j.ejpb.2014.07.012
  • 2014 • 334 Influence of zwitterionic SAMs on protein adsorption and the attachment of algal cells
    Bauer, S. and Alles, M. and Finlay, J.A. and Callow, J.A. and Callow, M.E. and Rosenhahn, A.
    Journal of Biomaterials Science, Polymer Edition 25 1530-1539 (2014)
    Zwitterionic polymers are non-fouling materials with immense potential for a range of biological applications. Here, we describe the resistance of zwitterionic self-assembled monolayers prepared from different solution ratios of positively and negatively charged thiols towards the adhesion of proteins, zoospores of the green alga Ulva linza, and cells of the unicellular alga Navicula perminuta. While mixed zwitterionic surfaces with a high hydrophilic nature significantly reduced the adhesion strength of the two algae, the positively and negatively charged components were far less effective. © 2014 Taylor and Francis.
    view abstractdoi: 10.1080/09205063.2014.929429
  • 2014 • 333 Is the antioxidative effectiveness of a bilberry extract influenced by encapsulation?
    Baum, M. and Schantz, M. and Leick, S. and Berg, S. and Betz, M. and Frank, K. and Rehage, H. and Schwarz, K. and Kulozik, U. and Schuchmann, H. and Richling, E.
    Journal of the Science of Food and Agriculture 94 2301-2307 (2014)
    BACKGROUND: Bilberries (Vaccinium myrtillus L.) have been suggested to have preventive properties against diseases associated with oxidative stress such as colon cancer or inflammatory bowel diseases. Therefore the gastrointestinal tract is regarded as a potential target for prevention. In this study the antioxidative properties of a commercially available anthocyanin-rich bilberry extract (BE) were investigated in comparison with four different BE-loaded microcapsule systems. As markers to describe the antioxidant status in this cellular system, intracellular reactive oxygen species (ROS) levels, oxidative DNA damage and total glutathione (tGSH) levels were monitored. RESULTS: Incubations with the BE-loaded capsule systems showed an increase in cellular glutathione levels and reduction of ROS levels at high BE concentrations (100-500 μg mL-1) and a positive effect on the formation of DNA strand breaks (5-10 μg mL-1 BE). The biological properties of BE-loaded pectin amide core-shell capsules, whey protein matrix capsules and coated apple pectin matrix capsules were comparable to those of the non-encapsulated BE. CONCLUSION: Overall, the BE and the encapsulated BE types tested have antioxidative activity under the studied assay conditions in terms of the prevention of oxidative DNA damage, the reduction of intracellular ROS and the enhancement of cellular tGSH. © 2014 Society of Chemical Industry.
    view abstractdoi: 10.1002/jsfa.6558
  • 2014 • 332 Effects of silver nitrate and silver nanoparticles on a planktonic community: General trends after short-term exposure
    Boenigk, J. and Beisser, D. and Zimmermann, S. and Bock, C. and Jakobi, J. and Grabner, D. and Großmann, L. and Rahmann, S. and Barcikowski, S. and Sures, B.
    PLoS ONE 9 (2014)
    Among metal pollutants silver ions are one of the most toxic forms, and have thus been assigned to the highest toxicity class. Its toxicity to a wide range of microorganisms combined with its low toxicity to humans lead to the development of a wealth of silver-based products in many bactericidal applications accounting to more than 1000 nano-technology-based consumer products. Accordingly, silver is a widely distributed metal in the environment originating from its different forms of application as metal, salt and nanoparticle. A realistic assessment of silver nanoparticle toxicity in natural waters is, however, problematic and needs to be linked to experimental approaches. Here we apply metatranscriptome sequencing allowing for elucidating reactions of whole communities present in a water sample to stressors. We compared the toxicity of ionic silver and ligand-free silver nanoparticles by short term exposure on a natural community of aquatic microorganisms. We analyzed the effects of the treatments on metabolic pathways and species composition on the eukaryote metatranscriptome level in order to describe immediate molecular responses of organisms using a community approach. We found significant differences between the samples treated with 5 μg/L AgNO 3 compared to the controls, but no significant differences in the samples treated with AgNP compared to the control samples. Statistical analysis yielded 126 genes (KO-IDs) with significant differential expression with a false discovery rate (FDR) < 0.05 between the control (KO) and AgNO3 (NO3) groups. A KEGG pathway enrichment analysis showed significant results with a FDR below 0.05 for pathways related to photosynthesis. Our study therefore supports the view that ionic silver rather than silver nanoparticles are responsible for silver toxicity. Nevertheless, our results highlight the strength of metatranscriptome approaches for assessing metal toxicity on aquatic communities. © 2014 Boenigk et al.
    view abstractdoi: 10.1371/journal.pone.0095340
  • 2014 • 331 Composition-structure-function diagrams of Ti-Ni-Au thin film shape memory alloys
    Buenconsejo, P.J.S. and Ludwig, Al.
    ACS Combinatorial Science 16 678-685 (2014)
    Ti-Ni-Au thin film materials libraries were prepared from multilayer precursors by combinatorial sputtering. The materials libraries were annealed at 500, 600, and 700 °C for 1 h and then characterized by high-throughput methods to investigate the relations between composition, structure and functional properties. The identified relations were visualized in functional phase diagrams. The goal is to identify composition regions that are suitable as high temperature shape memory alloys. Phase transforming compositions were identified by electrical resistance measured during thermal cycles in the range of -20 and 250 °C. Three phase transformation paths were confirmed: (1) B2-R, (2) B2-R-B19', and (3) B2-B19. For the materials library annealed at 500 °C only the B2-R transformation was observed. For the materials libraries annealed at 600 and 700 °C, all transformation paths were observed. High transformation temperatures (Ms ≈100 °C) were only obtained by annealing at 600 or 700 °C, and with compositions of Ti ≈ 50 at. % and Au &gt; 20 at. %. This is the composition range that undergoes B2-B19 transformation. The phase transformation behaviors were explained according to the compositional and annealing temperature dependence of phase/structure formation, as revealed by X-ray diffraction analysis of the materials libraries. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/co5000745
  • 2014 • 330 Photodeposition of copper and chromia on gallium oxide: The role of co-catalysts in photocatalytic water splitting
    Busser, G.W. and Mei, B. and Pougin, A. and Strunk, J. and Gutkowski, R. and Schuhmann, W. and Willinger, M.-G. and Schlögl, R. and Muhler, M.
    ChemSusChem 7 1030-1034 (2014)
    Split second: The photocatalytic activity of gallium oxide (β-Ga 2O3) depends strongly on the co-catalysts CuOx and chromia, which can be efficiently deposited in a stepwise manner by photoreduction of Cu2+ and CrO42-. The water-splitting activity can be tuned by varying the Cu loading in the range 0.025-1.5 wt %, whereas the Cr loading is not affecting the rate as long as small amounts (such as 0.05 wt %) are present. Chromia is identified as highly efficient co-catalyst in the presence of CuOx: it is essential for the oxidation of water. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.201301065
  • 2014 • 329 Analytic bond-order potentials for the bcc refractory metals Nb, Ta, Mo and W
    Čák, M. and Hammerschmidt, T. and Rogal, J. and Vitek, V. and Drautz, R.
    Journal of Physics Condensed Matter 26 (2014)
    Bond-order potentials (BOPs) are based on the tight-binding approximation for determining the energy of a system of interacting atoms. The bond energy and forces are computed analytically within the formalism of the analytic BOPs. Here we present parametrizations of the analytic BOPs for the bcc refractory metals Nb, Ta, Mo and W. The parametrizations are optimized for the equilibrium bcc structure and tested for atomic environments far from equilibrium that had not been included in the fitting procedure. These tests include structural energy differences for competing crystal structures; tetragonal, trigonal, hexagonal and orthorhombic deformation paths; formation energies of point defects as well as phonon dispersion relations. Our tests show good agreement with available experimental and theoretical data. In practice, we obtain the energetic ordering of vacancy, [1 1 1], [1 1 0], and [1 0 0] self-interstitial atom in agreement with density functional theory calculations. © 2014 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0953-8984/26/19/195501
  • 2014 • 328 A switchable peptide sensor for real-time lysosomal tracking
    Chen, L. and Wu, J. C. and Schmuck, C. and Tian, H.
    Chemical Communications 50 6443--6446 (2014)
    A bis-spiropyran functionalized peptide 1, which exhibits good cellpermeability, excellent biocompatibility and low cytotoxicity, has been developed for reversible and real-time lysosomal tracking.
    view abstractdoi: 10.1039/c4cc00670d
  • 2014 • 327 FT-IR and FT-Raman spectra of 5-fluoroorotic acid with solid state simulation by DFT methods
    Cuellar, A. and Alcolea Palafox, M. and Rastogi, V.K. and Kiefer, W. and Schlücker, S. and Rathor, S.K.
    Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy 132 430-445 (2014)
    FT-Raman and FT-IR studies of the biomolecule 5-fluoroorotic acid in the solid state were carried out. The unit cell found in the crystal was simulated as a tetramer form by density functional calculations. They were performed to clarify wavenumber assignments of the experimental observed bands in the spectra. Correlations with the molecule of uracil were made, and specific scale equations were employed to scale the wavenumbers of 5-fluoroorotic acid. Good reproduction of the experimental wavenumbers is obtained and the % error is very small in the majority of the bands. This fact confirms our simplified solid state model. The molecular structure was fully optimized using DFT and MP2 methods. The relative stability of both the syn and anti conformations was investigated, and the anti-form was found to be slightly more stable, by 7.49 kJ/mol at the MP2 level. The structures of all possible tautomeric forms were determined. The keto-form appeared as the most stable one. The NBO atomic charges and several thermodynamic parameters were also calculated. © 2014 Elsevier B.V. All rights reserved.
    view abstractdoi: 10.1016/j.saa.2014.04.107
  • 2014 • 326 Fetuin-A and albumin alter cytotoxic effects of calcium phosphate nanoparticles on human vascular smooth muscle cells
    Dautova, Y. and Kozlova, D. and Skepper, J.N. and Epple, M. and Bootman, M.D. and Proudfoot, D.
    PLoS ONE 9 (2014)
    Calcification is a detrimental process in vascular ageing and in diseases such as atherosclerosis and arthritis. In particular, small calcium phosphate (CaP) crystal deposits are associated with inflammation and atherosclerotic plaque de-stabilisation. We previously reported that CaP particles caused human vascular smooth muscle cell (VSMC) death and that serum reduced the toxic effects of the particles. Here, we found that the serum proteins fetuin-A and albumin (≥1 μM) reduced intracellular Ca2+ elevations and cell death in VSMCs in response to CaP particles. In addition, CaP particles functionalised with fetuin-A, but not albumin, were less toxic than naked CaP particles. Electron microscopic studies revealed that CaP particles were internalised in different ways; via macropinocytosis, membrane invagination or plasma membrane damage, which occurred within 10 minutes of exposure to particles. However, cell death did not occur until approximately 30 minutes, suggesting that plasma membrane repair and survival mechanisms were activated. In the presence of fetuin-A, CaP particle-induced damage was inhibited and CaP/plasma membrane interactions and particle uptake were delayed. Fetuin-A also reduced dissolution of CaP particles under acidic conditions, which may contribute to its cytoprotective effects after CaP particle exposure to VSMCs. These studies are particularly relevant to the calcification observed in blood vessels in patients with kidney disease, where circulating levels of fetuin-A and albumin are low, and in pathological situations where CaP crystal formation outweighs calcification-inhibitory mechanisms. © 2014 Dautova et al.
    view abstractdoi: 10.1371/journal.pone.0097565
  • 2014 • 325 Bloch-wave homogenization on large time scales and dispersive effective wave equations
    Dohnal, T. and Lamacz, A. and Schweizer, B.
    Multiscale Modeling and Simulation 12 488-513 (2014)
    We investigate second order linear wave equations in periodic media, aiming at the derivation of effective equations in Rn, n € {1, 2, 3}. Standard homogenization theory provides, for the limit of a small periodicity length ε &gt; 0, an effective second order wave equation that describes solutions on time intervals [0, T]. In order to approximate solutions on large time intervals [0, Tε-2], one has to use a dispersive, higher order wave equation. In this work, we provide a well-posed, weakly dispersive effective equation and an estimate for errors between the solution of the original heterogeneous problem and the solution of the dispersive wave equation. We use Bloch-wave analysis to identify a family of relevant limit models and introduce an approach to select a well-posed effective model under symmetry assumptions on the periodic structure. The analytical results are confirmed and illustrated by numerical tests. © 2014 Society for Industrial and Applied Mathematics.
    view abstractdoi: 10.1137/130935033
  • 2014 • 324 Structural and functional characterization of enamel pigmentation in shrews
    Dumont, M. and Tütken, T. and Kostka, A. and Duarte, M.J. and Borodin, S.
    Journal of Structural Biology 186 38-48 (2014)
    Pigmented tooth enamel occurs in several vertebrate clades, ranging from mammals to fish. Although an iron compound is associated with this orange to red colored pigmentation, its chemical and structural organization within the enamel is unknown. To determine the nature of the iron compound, we investigated heavily pigmented teeth of the northern short-tailed shrew Blarina brevicauda using combined characterization techniques such as scanning and transmission electron microscopy and synchrotron X-ray diffraction. We found that the pigmentation of the enamel with an iron content of around 8. wt% results from a close to amorphous magnetite phase deposited around the nm-sized enamel crystals. Furthermore, the influence of the pigmentation on the enamel hardness was determined by nanoindentation measurements. Finally, the biomechanical function and biological context are discussed in light of the obtained results. © 2014 Elsevier Inc.
    view abstractdoi: 10.1016/j.jsb.2014.02.006
  • 2014 • 323 Elemental composition of particulate matter and the association with lung function
    Eeftens, M. and Hoek, G. and Gruzieva, O. and Mölter, A. and Agius, R. and Beelen, R. and Brunekreef, B. and Custovic, A. and Cyrys, J. and Fuertes, E. and Heinrich, J. and Hoffmann, B. and De Hoogh, K. and Jedynska, A. and Keuke...
    Epidemiology 25 648-657 (2014)
    BACKGROUND: Negative effects of long-term exposure to particulate matter (PM) on lung function have been shown repeatedly. Spatial differences in the composition and toxicity of PM may explain differences in observed effect sizes between studies. METHODS: We conducted a multicenter study in 5 European birth cohorts - BAMSE (Sweden), GINIplus and LISAplus (Germany), MAAS (United Kingdom), and PIAMA (The Netherlands) - for which lung function measurements were available for study subjects at the age of 6 or 8 years. Individual annual average residential exposure to copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM smaller than 2.5 μm (PM2.5) and smaller than 10 μm (PM10) was estimated using land-use regression models. Associations between air pollution and lung function were analyzed by linear regression within cohorts, adjusting for potential confounders, and then combined by random effects meta-analysis. RESULTS: We observed small reductions in forced expiratory volume in the first second, forced vital capacity, and peak expiratory flow related to exposure to most elemental pollutants, with the most substantial negative associations found for nickel and sulfur. PM10 nickel and PM10 sulfur were associated with decreases in forced expiratory volume in the first second of 1.6% (95% confidence interval = 0.4% to 2.7%) and 2.3% (-0.1% to 4.6%) per increase in exposure of 2 and 200 ng/m, respectively. Associations remained after adjusting for PM mass. However, associations with these elements were not evident in all cohorts, and heterogeneity of associations with exposure to various components was larger than for exposure to PM mass. CONCLUSIONS: Although we detected small adverse effects on lung function associated with annual average levels of some of the evaluated elements (particularly nickel and sulfur), lower lung function was more consistently associated with increased PM mass. Copyright © 2014 by Lippincott Williams & Wilkins.
    view abstractdoi: 10.1097/EDE.0000000000000136
  • 2014 • 322 Ultrastructural organization and micromechanical properties of shark tooth enameloid
    Enax, J. and Janus, A.M. and Raabe, D. and Epple, M. and Fabritius, H.-O.
    Acta Biomaterialia 10 3959-3968 (2014)
    The outer part of shark teeth is formed by the hard and mineral-rich enameloid that has excellent mechanical properties, which makes it a very interesting model system for the development of new bio-inspired dental materials. We characterized the microstructure, chemical composition and resulting local mechanical properties of the enameloid from teeth of Isurus oxyrinchus (shortfin mako shark) by performing an in-depth analysis using various high-resolution analytical techniques, including scanning electron microscopy, qualitative energy-dispersive X-ray spectroscopy and nanoindentation. Shark tooth enameloid reveals an intricate hierarchical arrangement of thin (50-80 nm) and long (>1 μm) crystallites of fluoroapatite with a high degree of structural anisotropy, which leads to exceptional mechanical properties. Both stiffness and hardness are surprisingly homogeneous in the shiny layer as well as in the enameloid: although both tooth phases differ in structure and composition, they show almost no orientation dependence with respect to the loading direction of the enameloid crystallites. The results were used to determine the structural hierarchy of shark teeth, which can be used as a base for establishing design criteria for synthetic bio-inspired and biomimetic dental composites. © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
    view abstractdoi: 10.1016/j.actbio.2014.04.028
  • 2014 • 321 Mixed layers of β-lactoglobulin and SDS at air-water interfaces with tunable intermolecular interactions
    Engelhardt, K. and Weichsel, U. and Kraft, E. and Segets, D. and Peukert, W. and Braunschweig, B.
    Journal of Physical Chemistry B 118 4098-4105 (2014)
    Mixtures of β-lactoglobulin (BLG) and sodium dodecyl sulfate (SDS) were studied at pH 3.8 and 6.7 under equilibrium conditions. At these pH conditions, BLG carries either a positive or a negative net charge, respectively, which enables tunable electrostatic interactions between anionic SDS surfactants and BLG proteins. For pH 3.8, vibrational sum-frequency generation (SFG) and ellipsometry indicate strong BLG-SDS complex formation at air-water interfaces that is caused by attractive electrostatic interactions. The latter complexes are already formed in the bulk solution which was confirmed by a thermodynamic study of BLG-SDS mixtures using isothermal titration calorimetry (ITC). For acidic conditions we determine from our ITC data an exothermal binding enthalpy of -40 kJ mol-1. Increasing SDS/BLG molar ratios above 10 leads to a surface excess of SDS and thus to a charge reversal from a positive net charge with BLG as the dominating surface adsorbed species to a negatively charged layer with SDS as the dominating surface species. The latter is evidenced by a pronounced minimum in SFG intensities that is also accompanied by a phase change of O-H stretching bands due to a reorientation of H2O within the local electric field. This phase change which occurs at SDS/BLG molar ratio between 1 and 10 causes a polarity change in SFG intensities from BLG aromatic C-H stretching vibrations. Conclusions from SFG spectra are corroborated by ellipsometry which shows a dramatic increase in layer thicknesses at molar ratios where a charge reversal occurs. The formation of interfacial multilayers comprising SDS-BLG complexes is, thus, caused by cancellation of electrostatic interactions which leads to agglomeration at the interface. In contrast to pH 3.8, behavior of BLG-SDS mixtures at pH 6.7 is different due to repulsive electrostatic interactions between SDS and BLG which lead to a significantly reduced binding enthalpy of -17 kJ mol-1. Finally, it has to be mentioned that SFG spectra show a coexistence of BLG and SDS molecules at the interface for BLG-SDS molar ratios &gt; 2. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/jp501541q
  • 2014 • 320 A facile method for preparation of tailored scaffolds for DNA-origami
    Erkelenz, M. and Bauer, D.M. and Meyer, R. and Gatsogiannis, C. and Raunser, S. and Saccà, B. and Niemeyer, C.M.
    Small 10 73-77 (2014)
    A convenient PCR cloning strategy allows one to prepare hundreds of picomoles of circular single-stranded DNA molecules, which are suitable as scaffolds for the assembly of DNA origami structures. The method is based on a combination of site-directed mutagenesis and site- and ligation-independent cloning protocols, with simultaneous insertion of a nicking endonuclease restriction site on a double-stranded plasmid of desired length and sequence. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/smll.201300701
  • 2014 • 319 Structural complexity in metal-organic frameworks: Simultaneous modification of open metal sites and hierarchical porosity by systematic doping with defective linkers
    Fang, Z. and Dürholt, J.P. and Kauer, M. and Zhang, W. and Lochenie, C. and Jee, B. and Albada, B. and Metzler-Nolte, N. and Pöppl, A. and Weber, B. and Muhler, M. and Wang, Y. and Schmid, R. and Fischer, R.A.
    Journal of the American Chemical Society 136 9627-9636 (2014)
    A series of defect-engineered metal-organic frameworks (DEMOFs) derived from parent microporous MOFs was obtained by systematic doping with defective linkers during synthesis, leading to the simultaneous and controllable modification of coordinatively unsaturated metal sites (CUS) and introduction of functionalized mesopores. These materials were investigated via temperature-dependent adsorption/desorption of CO monitored by FTIR spectroscopy under ultra-high-vacuum conditions. Accurate structural models for the generated point defects at CUS were deduced by matching experimental data with theoretical simulation. The results reveal multivariate diversity of electronic and steric properties at CUS, demonstrating the MOF defect structure modulation at two length scales in a single step to overcome restricted active site specificity and confined coordination space at CUS. Moreover, the DEMOFs exhibit promising modified physical properties, including band gap, magnetism, and porosity, with hierarchical micro/mesopore structures correlated with the nature and the degree of defective linker incorporation into the framework. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/ja503218j
  • 2014 • 318 Shear-Modulus investigations of monohydroxy alcohols: Evidence for a short-chain-polymer rheological response
    Gainaru, C. and Figuli, R. and Hecksher, T. and Jakobsen, B. and Dyre, J.C. and Wilhelm, M. and Böhmer, R.
    Physical Review Letters 112 (2014)
    Liquids composed of small-molecule monohydroxy alcohols are demonstrated to display rheological behavior typical for oligomeric chains. This observation was made possible by rheological experiments in which more than seven decades in frequency and more than five decades on the mechanical modulus scale are covered. The singly hydrogen-bonded monohydroxy alcohols were chosen because they display significant, but surprisingly poorly understood effects of intermolecular association. Based on the present shear study, one can apply theoretical concepts of polymer science to understand the anomalous physical behavior of a wide range of hydrogen-bonded liquids. © 2014 American Physical Society.
    view abstractdoi: 10.1103/PhysRevLett.112.098301
  • 2014 • 317 Solid state anion-π interactions involving polyhalides
    Giese, M. and Albrecht, M. and Bohnen, C. and Repenko, T. and Valkonen, A. and Rissanen, K.
    Dalton Transactions 43 1873-1880 (2014)
    The stabilization of polyhalides in the solid state with the support of electron-deficient pentafluorophenyl groups is described. Furthermore, a synthetic approach towards the sensitive tetraiodide dianion is described and ESI mass spectrometric evidence for its presence in solution is reported. © The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c3dt52960f
  • 2014 • 316 Support and challenges to the melanosomal casing model based on nanoscale distribution of metals within iris melanosomes detected by X-ray fluorescence analysis
    Gorniak, T. and Haraszti, T. and Suhonen, H. and Yang, Y. and Hedberg-Buenz, A. and Koehn, D. and Heine, R. and Grunze, M. and Rosenhahn, A. and Anderson, M.G.
    Pigment Cell and Melanoma Research 27 831-834 (2014)
    Melanin within melanosomes exists as eumelanin or pheomelanin. Distributions of these melanins have been studied extensively within tissues, but less often within individual melanosomes. Here, we apply X-ray fluorescence analysis with synchrotron radiation to survey the nanoscale distribution of metals within purified melanosomes of mice. The study allows a discovery-based characterization of melanosomal metals, and, because Cu is specifically associated with eumelanin, a hypothesis-based test of the 'casing model' predicting that melanosomes contain a pheomelanin core surrounded by a eumelanin shell. Analysis of Cu, Ca, and Zn shows variable concentrations and distributions, with Ca/Zn highly correlated, and at least three discrete patterns for the distribution of Cu vs. Ca/Zn in different melanosomes - including one with a Cu-rich shell surrounding a Ca/Zn-rich core. Thus, the results support predictions of the casing model, but also suggest that in at least some tissues and genetic contexts, other arrangements of melanin may co-exist. © 2014 John Wiley & Sons A/S.
    view abstractdoi: 10.1111/pcmr.12278
  • 2014 • 315 Hydrogels from phospholipid vesicles
    Gräbner, D. and Hoffmann, H. and Förster, S. and Rosenfeldt, S. and Linders, J. and Mayer, C. and Talmon, Y. and Schmidt, J.
    Advances in Colloid and Interface Science 208 252-263 (2014)
    It is shown that phospholipid dispersions with a few percent of diacylphosphocholine PC in water can be swollen to single-phase lyotropic liquid crystalline Lα-phases by the addition of co-solvents like glycerol, 1,3-butyleneglycol BG or 1,2-propyleneglycol PG. The birefringent Lα-phases contain small unilamellar and multilamellar vesicles if the temperature of the samples is above the Krafft-Temperature Tm of the phospholipid. When such transparent birefringent viscous samples are cooled down below Tm the samples are transformed into birefringent gels. Cryo-TEM and FF-TEM measurements show that the bilayers of the vesicles are transformed from the liquid to the crystalline state during the transformation while the vesicle structure remains. The bilayers of the crystalline vesicles form adhesive contacts in the gel. Pulsed-field gradient NMR measurements show that two different kinds of water or co-solvent can be distinguished in the gels. One type of solvent molecules can diffuse like normal solvent in a continuous bulk phase. A second type of water diffuses much more slowly. This type of solvent is obviously trapped in the vesicles. The permeability of the crystalline vesicles for water and solvent molecules is much lower in the crystalline state than in the fluid state. Maximum swelling of the diacylphosphocholin dispersions occurs when the refractive index of the solvent is matched to the refractive index of the bilayers. The attraction between the bilayers is at a minimum in this state and the liquid crystalline L α-phase's undulation forces between the bilayers push the bilayers apart. On transformation to the gel state the crystalline bilayers assume a high elastic bending rigidity. Undulations of the bilayers are now suppressed, and the bilayers can form adhesive contacts. Oscillating rheological measurements show that the gels with only 1% of phospholipids can have a storage modulus of 1000 Pa. The gels are very brittle. They break when they are deformed by a few percent. © 2014 Elsevier B.V.
    view abstractdoi: 10.1016/j.cis.2014.02.011
  • 2014 • 314 Intermolecular interactions in highly concentrated protein solutions upon compression and the role of the solvent
    Grobelny, S. and Erlkamp, M. and Möller, J. and Tolan, M. and Winter, R.
    Journal of Chemical Physics 141 (2014)
    The influence of high hydrostatic pressure on the structure and protein-protein interaction potential of highly concentrated lysozyme solutions up to about 370 mg ml1was studied and analyzed using small-angle X-ray scattering in combination with a liquid-state theoretical approach. In the concentration region below 200 mg ml1, the interaction parameters of lysozyme solutions are affected by pressure in a nonlinear way, which is probably due to significant changes in the structural properties of bulk water, i.e., due to a solvent-mediated effect. Conversely, for higher concentrated protein solutions, where hydration layers below ∼4 water molecules are reached, the interaction potential turns rather insensitive to compression. The onset of transient (dynamic) clustering is envisaged in this concentration range. Our results also show that pressure suppresses protein nucleation, aggregation and finally crystallization in supersaturated condensed protein solutions. These findings are of importance for controlling and fine-tuning protein crystallization. Moreover, these results are also important for understanding the high stability of highly concentrated protein solutions (as they occur intracellularly) in organisms thriving under hydrostatic pressure conditions such as in the deep sea, where pressures up to the kbar-level are reached. © 2014 AIP Publishing LLC.
    view abstractdoi: 10.1063/1.4895542
  • 2014 • 313 Polyalkylcyanoacrylate nanocapsules: Variation of membrane permeability by chemical cross-linking
    Gross-Heitfeld, C. and Linders, J. and Appel, R. and Selbach, F. and Mayer, C.
    Journal of Physical Chemistry B 118 4932-4939 (2014)
    The permeability of the polymer walls of polyalkylcyanoacrylate nanocapsules varies by different degrees of chemical cross-linking. For this reason, different amounts of bivalent alkylcyanoacrylates are added to the monovalent alkylcyanoacrylate prior to an interfacial polymerization step in order to generate capsules with various cross-linking densities. The obtained nanocapsules are characterized by observing the water molecules via pulsed field-gradient nuclear magnetic resonance using a stimulated echo sequence. The resulting echo decay plots reveal the exchange rate of the water molecules between the free and encapsulated states. The observed dwell times of water molecules in the encapsulated state are characteristic parameters for the permeability of the given capsule membranes. They show a clear dependence on the degree of cross-linking, proving the potential of this approach for a controlled variation of the capsule permeability. Also, the cross-linked nanocapsules exhibit a significantly decreased solubility in tetrahydrofuran which may lead to new applications for polyalkylcyanoacrylate nanocapsules in organic solvents. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/jp5003098
  • 2014 • 312 Biotribology of a vitamin E-stabilized polyethylene for hip arthroplasty - Influence of artificial ageing and third-body particles on wear
    Grupp, T.M. and Holderied, M. and Mulliez, M.A. and Streller, R. and Jäger, M. and Blömer, W. and Utzschneider, S.
    Acta Biomaterialia 10 3068-3078 (2014)
    The objective of our study was to evaluate the influence of prolonged artificial ageing on oxidation resistance and the subsequent wear behaviour of vitamin E-stabilized, in comparison to standard and highly cross-linked remelted polyethylene (XLPE), and the degradation effect of third-body particles on highly cross-linked remelted polyethylene inlays in total hip arthroplasty. Hip wear simulation was performed with three different polyethylene inlay materials (standard: γ-irradiation 30 kGy, N2; highly cross-linked and remelted: γ-irradiation 75 kGy, EO; highly cross-linked and vitamin E (0.1%) blended: electron beam 80 kGy, EO) machined from GUR 1020 in articulation with ceramic and cobalt-chromium heads. All polyethylene inserts beneath the virgin references were subjected to prolonged artificial ageing (70 °C, pure oxygen at 5 bar) with a duration of 2, 4, 5 or 6 weeks. In conclusion, after 2 weeks of artificial ageing, standard polyethylene shows substantially increased wear due to oxidative degradation, whereas highly cross-linked remelted polyethylene has a higher oxidation resistance. However, after enhanced artificial ageing for 5 weeks, remelted XLPE also starts oxidate, in correlation with increased wear. Vitamin E-stabilized polyethylene is effective in preventing oxidation after irradiation cross-linking even under prolonged artificial ageing for up to 6 weeks, resulting in a constant wear behaviour. © 2014 Published by Elsevier Ltd. on behalf of Acta Materialia Inc.
    view abstractdoi: 10.1016/j.actbio.2014.02.052
  • 2014 • 311 Redox hydrogels with adjusted redox potential for improved efficiency in Z-scheme inspired biophotovoltaic cells
    Hartmann, V. and Kothe, T. and Pöller, S. and El-Mohsnawy, E. and Nowaczyk, M.M. and Plumeré, N. and Schuhmann, W. and Rögner, M.
    Physical Chemistry Chemical Physics 16 11936-11941 (2014)
    The improvement of Z-scheme inspired biophotovoltaics is achieved by fine tuning the properties of redox hydrogels applied as immobilization and electron conducting matrices for the photosystem-protein complexes. The formal potentials of the redox hydrogels are adjusted to the respective redox sites in the photosystems for optimized electron transfer without substantial voltage loss. The anode is based on photosystem 2 (PS2) integrated in a phenothiazine modified redox hydrogel with a formal potential of -1 mV vs. SHE, which is 59 mV more positive than the QB acceptor site in PS2. The cathode is based on photosystem 1 (PS1) contacted via an Os-complex based redox hydrogel with a formal potential of 395 mV vs. SHE, i.e. 28 mV more negative than the primary P700 electron acceptor of PS1. The potential difference between the two redox hydrogels is 396 mV. An open circuit voltage (VOC) of 372.5 ± 2.1 mV could be achieved for the biophotovoltaic cell. The maximum power output is 1.91 ± 0.56 μW cm-2 and the conversion efficiency (η) is 4.5 × 10-5, representing a 125-fold improvement in comparison to the previously proposed device exploiting the photosynthetic Z-scheme for electrical energy production. © 2014 the Partner Organisations.
    view abstractdoi: 10.1039/c4cp00380b
  • 2014 • 310 Parameterized electronic description of carbon cohesion in iron grain boundaries
    Hatcher, N. and Madsen, G.K.H. and Drautz, R.
    Journal of Physics Condensed Matter 26 (2014)
    We employ a recently developed iron-carbon orthogonal tight-binding model in calculations of carbon in iron grain boundaries. We use the model to evaluate the properties of carbon near and on the Σ5 (3 1 0)[0 0 1] symmetric tilt grain boundary (GB) in iron, and calculations show that a carbon atom lowers the GB energy by 0.29 eV/atom in accordance with DFT. Carbon segregation to the GB is analyzed, and we find an energy barrier of 0.92 eV for carbon to segregate to the carbon-free interface while segregation to a fully filled interface is disfavored. Local volume (via Voronoi tessellation), magnetic, and electronic effects are correlated with atomic energy changes, and we isolate two different mechanisms governing carbon's behavior in iron: a volumetric strain which increases the energy of carbon in interstitial α iron and a non-strained local bonding which stabilizes carbon at the GB. © 2014 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0953-8984/26/14/145502
  • 2014 • 309 Acidity in DMSO from the embedded cluster integral equation quantum solvation model
    Heil, J. and Tomazic, D. and Egbers, S. and Kast, S.M.
    Journal of Molecular Modeling 20 (2014)
    The embedded cluster reference interaction site model (EC-RISM) is applied to the prediction of acidity constants of organic molecules in dimethyl sulfoxide (DMSO) solution. EC-RISM is based on a self-consistent treatment of the solute's electronic structure and the solvent's structure by coupling quantum-chemical calculations with three-dimensional (3D) RISM integral equation theory. We compare available DMSO force fields with reference calculations obtained using the polarizable continuum model (PCM). The results are evaluated statistically using two different approaches to eliminating the proton contribution: a linear regression model and an analysis of pKa shifts for compound pairs. Suitable levels of theory for the integral equation methodology are benchmarked. The results are further analyzed and illustrated by visualizing solvent site distribution functions and comparing them with an aqueous environment. © Springer-Verlag 2014.
    view abstractdoi: 10.1007/s00894-014-2161-4
  • 2014 • 308 Dose-dependent surface endothelialization and biocompatibility of polyurethane noble metal nanocomposites
    Hess, C. and Schwenke, A. and Wagener, P. and Franzka, S. and Laszlo Sajti, C. and Pflaum, M. and Wiegmann, B. and Haverich, A. and Barcikowski, S.
    Journal of Biomedical Materials Research - Part A 102 1909-1920 (2014)
    Surface pre-endothelialization is a promising approach to improve the hemocompatibility of implants, medical devices, and artificial organs. To promote the adhesive property of thermoplastic polyurethane (TPU) for endothelial cells (ECs), up to 1 wt % of gold (Au) or platinum (Pt) nanoparticles, fabricated by pulsed laser ablation in polymer solution, were embedded into the polymer matrix. The analysis of these nanocomposites showed a homogenous dispersion of the nanoparticles, with average diameters of 7 nm for Au or 9 nm for Pt. A dose-dependent effect was found when ECs were seeded onto nanocomposites comprising different nanoparticle concentrations, resulting in a fivefold improvement of proliferation at 0.1 wt % nanoparticle load. This effect was associated with a nanoparticle concentration-dependent hydrophilicity and negative charge of the nanocomposite. In dynamic flow tests, nanocomposites containing 0.1 wt % Au or Pt nanoparticles allowed for the generation of a confluent and resistant EC layer. Real-time polymerase chain reaction quantification of specific markers for EC activation indicated that ECs cultivated on nanocomposites remain in an inactivated, nonthrombogenic and noninflammatory state; however, maintain the ability to trigger an inflammatory response upon stimulation. These findings were confirmed by a platelet and leukocyte adhesion assay. The results of this study suggest the possible applicability of TPU nanocomposites, containing 0.1 wt % Au or Pt nanoparticles, for the generation of pre-endothelialized surfaces of medical devices. © 2013 Wiley Periodicals, Inc.
    view abstractdoi: 10.1002/jbm.a.34860
  • 2014 • 307 A thermodynamic investigation of the glucose-6-phosphate isomerization
    Hoffmann, P. and Held, C. and Maskow, T. and Sadowski, G.
    Biophysical Chemistry 195 22-31 (2014)
    In this work, ΔRg+ values for the enzymatic G6P isomerization were determined as a function of the G6P equilibrium molality between 25 °C and 37 °C. The reaction mixtures were buffered at pH = 8.5. In contrast to standard literature work, ΔRg+ values were determined from activity-based equilibrium constants instead of molality-based apparent values. This yielded a ΔRg+ value of 2.55 ± 0.05 kJ mol- 1 at 37 °C, independent of the solution pH between 7.5 and 8.5. Furthermore, ΔRh + was measured at pH = 8.5 and 25 °C yielding 12.05 ± 0.2 kJ mol- 1. Accounting for activity coefficients turned out to influence ΔRg+ up to 30% upon increasing the G6P molality. This result was confirmed by predictions using the thermodynamic model ePC-SAFT. Finally, the influence of the buffer and of potassium glutamate as an additive on the reaction equilibrium was measured and predicted with ePC-SAFT in good agreement. © 2014 Elsevier B.V.
    view abstractdoi: 10.1016/j.bpc.2014.08.002
  • 2014 • 306 Tailoring the morphology of mesoporous titania thin films through biotemplating with nanocrystalline cellulose
    Ivanova, A. and Fattakhova-Rohlfing, D. and Kayaalp, B.E. and Rathouský, J. and Bein, T.
    Journal of the American Chemical Society 136 5930-5937 (2014)
    The tunable porosity of titania thin films is a key factor for successful applications in photovoltaics, sensing, and photocatalysis. Here, we report on nanocrystalline cellulose (NCC) as a novel shape-persistent templating agent enabling the straightforward synthesis of mesoporous titania thin films. The obtained structures are highly porous anatase morphologies having well-defined, narrow pore size distributions. By varying the titania-to-template ratio, it is possible to tune the surface area, pore size, pore anisotropy, and dimensions of titania crystallites in the films. Moreover, a post-treatment at high humidity and subsequent slow template removal can be used to achieve pore widening; this treatment is also beneficial for the multilayer deposition of thick films. The resulting homogeneous transparent films can be directly spin- or dip- coated on glass, silicon, and transparent conducting oxide (TCO) substrates. The mesoporous titania films show very high activity in the photocatalytic NO conversion and in the degradation of 4-chlorophenol. Furthermore, the films can be successfully applied as anodes in dye-sensitized solar cells. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/ja411292u
  • 2014 • 305 The development of chiral nematic mesoporous materials
    Kelly, J.A. and Giese, M. and Shopsowitz, K.E. and Hamad, W.Y. and MacLachlan, M.J.
    Accounts of Chemical Research 47 1088-1096 (2014)
    ConspectusCellulose nanocrystals (CNCs) are obtained from the sulfuric acid-catalyzed hydrolysis of bulk cellulose. The nanocrystals have diameters of ∼5-15 nm and lengths of ∼100-300 nm (depending on the cellulose source and hydrolysis conditions). This lightweight material has mostly been investigated to reinforce composites and polymers because it has remarkable strength that rivals carbon nanotubes. But CNCs have an additional, less explored property: they organize into a chiral nematic (historically referred to as cholesteric) liquid crystal in water. When dried into a thin solid film, the CNCs retain the helicoidal chiral nematic order and assemble into a layered structure where the CNCs have aligned orientation within each layer, and their orientation rotates through the stack with a characteristic pitch (repeating distance). The cholesteric ordering can act as a 1-D photonic structure, selectively reflecting circularly polarized light that has a wavelength nearly matching the pitch.During CNC self-assembly, it is possible to add sol-gel precursors, such as Si(OMe)4, that undergo hydrolysis and condensation as the solvent evaporates, leading to a chiral nematic silica/CNC composite material. Calcination of the material in air destroys the cellulose template, leaving a high surface area mesoporous silica film that has pore diameters of ∼3-10 nm. Importantly, the silica is brilliantly iridescent because the pores in its interior replicate the chiral nematic structure. These films may be useful as optical filters, reflectors, and membranes.In this Account, we describe our recent research into mesoporous films with chiral nematic order. Taking advantage of the chiral nematic order and nanoscale of the CNC templates, new functional materials can be prepared. For example, heating the silica/CNC composites under an inert atmosphere followed by removal of the silica leaves highly ordered, mesoporous carbon films that can be used as supercapacitor electrodes. The composition of the mesoporous films can be varied by using assorted organosilica precursors. After removal of the cellulose by acid-catalyzed hydrolysis, highly porous, iridescent organosilica films are obtained. These materials are flexible and offer the ability to tune the chemical and mechanical properties through variation of the organic spacer.Chiral nematic mesoporous silica and organosilica materials, obtainable as centimeter-scale freestanding films, are interesting hosts for nanomaterials. When noble metal nanoparticles are incorporated into the pores, they show strong circular dichroism signals associated with their surface plasmon resonances that arise from dipolar coupling of the particles within the chiral nematic host. Fluorescent conjugated polymers show induced circular dichroism spectra when encapsulated in the chiral nematic host. The porosity, film structure, and optical properties of these materials could enable their use in sensors.We describe the development of chiral nematic mesoporous silica and organosilica, demonstrate different avenues of host-guest chemistry, and identify future directions that exploit the unique combination of properties present in these materials. The examples covered in this Account demonstrate that there is a rich diversity of composite materials accessible using CNC templating. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/ar400243m
  • 2014 • 304 Photoemission electron microscopy and scanning electron microscopy of magnetospirillum magnetotacticum 's magnetosome chains
    Keutner, C. and Von Bohlen, A. and Berges, U. and Espeter, P. and Schneider, C.M. and Westphal, C.
    Analytical Chemistry 86 9590-9594 (2014)
    Magnetotactic bacteria are of great interdisciplinary interest, since a vast field of applications from magnetic recording media to medical nanorobots is conceivable. A key feature for a further understanding is the detailed knowledge about the magnetosome chain within the bacteria. We report on two preparation procedures suitable for UHV experiments in reflective geometry. Further, we present the results of scanning electron microscopy, as well as the first photoemission electron microscopy experiments, both accessing the magnetosomes within intact magnetotactic bacteria and compare these to scanning electron microscopy data from the literature. From the images, we can clearly identify individual magnetosomes within their chains. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/ac502050j
  • 2014 • 303 Temperature-driven adsorption and desorption of proteins at solid-liquid interfaces
    Kiesel, I. and Paulus, M. and Nase, J. and Tiemeyer, S. and Sternemann, C. and Rüster, K. and Wirkert, F.J. and Mende, K. and Büning, T. and Tolan, M.
    Langmuir 30 2077-2083 (2014)
    The heat-induced desorption and adsorption of the proteins lysozyme, ribonuclease A, bovine serum albumin, and fibronectin at protein layers was investigated in two different environments: pure buffer and protein solution. Using two different environments allows us to distinguish between thermodynamic and kinetic mechanisms in the adsorption process. We observed a desorption in buffer and an adsorption in protein solution, depending upon protein properties, such as size, stability, and charge. We conclude that the desorption in buffer is mainly influenced by the mobility of the proteins at the interface, while the adsorption in protein solution is driven by conformational changes and, thereby, a gain in entropy. These results are relevant for controlling biofilm formation at solid-liquid interfaces. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/la404884a
  • 2014 • 302 Preparation and antimalarial activity of a novel class of carbohydrate-derived, fused thiochromans
    Kinfe, H. H. and Moshapo, P. T. and Makolo, F. L. and Gammon, D. W. and Ehlers, M. and Schmuck, C.
    European Journal of Medicinal Chemistry 87 197--202 (2014)
    A novel class of fused thiochroman derivatives has been prepared by an efficient and versatile synthetic procedure involving nucleophilic displacement of the side-chain iodo substituent in 2-deoxy-2-C-iodomethyl glucosides by thiophenolate ions, and subsequent intramolecular C-glycoside formation. A range of aromatic substituents is tolerated, and the subsequent facile selective oxidation of the sulfur to the sulfoxide or sulfone level expands the range and molecular diversity of the series of compounds. A selection of the sulfoxide and sulfone derivatives bearing lipophilic substituents on the aromatic portion were found to have antimalarial activities in the low micromolar range. (C) 2014 Elsevier Masson SAS. All rights reserved.
    view abstractdoi: 10.1016/j.ejmech.2014.09.060
  • 2014 • 301 Vertical distribution of overpotentials and irreversible charge losses in lithium ion battery electrodes
    Klink, S. and Schuhmann, W. and La Mantia, F.
    ChemSusChem 7 2159-2166 (2014)
    Porous lithium ion battery electrodes are characterized using a vertical distribution of cross-currents. In an appropriate simplification, this distribution can be described by a transmission line model (TLM) consisting of infinitely thin electrode layers. To investigate the vertical distribution of currents, overpotentials, and irreversible charge losses in a porous graphite electrode in situ, a multi-layered working electrode (MWE) was developed as the experimental analogue of a TLM. In this MWE, each layer is in ionic contact but electrically insulated from the other layers by a porous separator. It was found that the negative graphite electrodes get lithiated and delithiated stage-by-stage and layer-by-layer. Several mass-transport- as well as non-mass-transport-limited processes could be identified. Local current densities can reach double the average, especially on the outermost layer at the beginning of each intercalation stage. Furthermore, graphite particles close to the counter electrode act as "electrochemical sieve" reducing the impurities present in the electrolyte such as water. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.201400056
  • 2014 • 300 Prophylactic and therapeutic vaccination with a nanoparticle-based peptide vaccine induces efficient protective immunity during acute and chronic retroviral infection
    Knuschke, T. and Bayer, W. and Rotan, O. and Sokolova, V. and Wadwa, M. and Kirschning, C.J. and Hansen, W. and Dittmer, U. and Epple, M. and Buer, J. and Westendorf, A.M.
    Nanomedicine: Nanotechnology, Biology, and Medicine 10 1787-1798 (2014)
    Retroviral infections e.g. HIV still represent a unique burden in the field of vaccine research. A common challenge in vaccine design is to find formulations that create appropriate immune responses to protect against and/or control the given pathogen. Nanoparticles have been considered to be ideal vaccination vehicles that mimic invading pathogens. In this study, we present biodegradable calcium phosphate (CaP) nanoparticles, functionalized with CpG and retroviral T cell epitopes of Friend virus (FV) as excellent vaccine delivery system. CaP nanoparticles strongly increased antigen delivery to antigen-presenting cells to elicit a highly efficient T cell-mediated immune response against retroviral FV infection. Moreover, single-shot immunization of chronically FV-infected mice with functionalized CaP nanoparticles efficiently reactivated effector T cells which led to a significant decrease in viral loads. Thus, our findings clearly indicate that a nanoparticle-based peptide immunization is a promising approach to improve antiretroviral vaccination. From the Clinical Editor: In this study, biodegradable calcium phosphate nanoparticles were used as a vaccine delivery system after functionalization with CpG and Friend virus-derived T-cell epitopes. This vaccination strategy resulted in increased T-cell mediated immune response even in chronically infected mice, providing a promising approach to the development of clinically useful antiretroviral vaccination strategies. © 2014 Elsevier Inc.
    view abstractdoi: 10.1016/j.nano.2014.06.014
  • 2014 • 299 Spheronization process particle kinematics determined by discrete element simulations and particle image velocimentry measurements
    Koester, M. and García, R.E. and Thommes, M.
    International Journal of Pharmaceutics 477 81-87 (2014)
    Spheronization is an important pharmaceutical manufacturing technique to produce spherical agglomerates of 0.5-2 mm diameter. These pellets have a narrow size distribution and a spherical shape. During the spheronization process, the extruded cylindrical strands break in short cylinders and evolve from a cylindrical to a spherical state by deformation and attrition/agglomeration mechanisms. Using the discrete element method, an integrated modeling-experimental framework is presented, that captures the particle motion during the spheronization process. Simulations were directly compared and validated against particle image velocimetry (PIV) experiments with monodisperse spherical and dry γ-Al2O3 particles. Result demonstrate a characteristic torus like flow pattern, with particle velocities about three times slower than the rotation speed of the friction plate. Five characteristic zones controlling the spheronization process are identified: Zone I, where particles undergo shear forces that favors attrition and contributes material to the agglomeration process; Zone II, where the static wall contributes to the mass exchange between particles; Zone III, where gravitational forces combined with particle motion induce particles to collide with the moving plate and re-enter Zone I; Zone IV, where a subpopulation of particles are ejected into the air when in contact with the friction plate structure; and Zone V where the low poloidal velocity favors a stagnant particle population and is entirely controlled by the batch size. These new insights in to the particle motion are leading to deeper process understanding, e.g., the effect of load and rotation speed to the pellet formation kinetics. This could be beneficial for the optimization of a manufacturing process as well as for the development of new formulations. © 2014 Elsevier B.V. All rights reserved.
    view abstractdoi: 10.1016/j.ijpharm.2014.10.007
  • 2014 • 298 Investigations on the activity of poly(2-oxazoline) enzyme conjugates dissolved in organic solvents
    Konieczny, S. and Krumm, C. and Doert, D. and Neufeld, K. and Tiller, J.C.
    Journal of Biotechnology 181 55-63 (2014)
    The use of enzymes in organic solvents offers a great opportunity for the highly selective synthesis of complex organic compounds. In this study we investigate the POXylation of several enzymes with different polyoxazolines ranging from the hydrophilic poly(2-methyl-oxazoline) (PMOx) to the hydrophobic poly(2-heptyl-oxazoline) (PHeptOx). As reported previously on the examples of model enzymes POXylation mediated by pyromellitic acid dianhydride results in highly modified, organosoluble protein conjugates. This procedure is here extended to a larger number of proteins and optimized for the different polyoxazolines. The resulting polymer-enzyme conjugates (PEC) became soluble in different organic solvents ranging from hydrophilic DMF to even toluene. These conjugates were characterized regarding their solubility and especially their activity in organic solvents and in some cases the PECs showed significantly (up to 153,000 fold) higher activities than the respective native enzymes. © 2014 Elsevier B.V.
    view abstractdoi: 10.1016/j.jbiotec.2014.03.035
  • 2014 • 297 Multifunctional, defect-engineered metal-organic frameworks with ruthenium centers: Sorption and catalytic properties
    Kozachuk, O. and Luz, I. and Llabrés I Xamena, F.X. and Noei, H. and Kauer, M. and Albada, H.B. and Bloch, E.D. and Marler, B. and Wang, Y. and Muhler, M. and Fischer, R.A.
    Angewandte Chemie - International Edition 53 7058-7062 (2014)
    A mixed-linker solid-solution approach was employed to modify the metal sites and introduce structural defects into the mixed-valence Ru II/III structural analogue of the well-known MOF family [M 3 II,II(btc)2] (M=Cu, Mo, Cr, Ni, Zn; btc=benzene-1,3,5-tricarboxylate), with partly missing carboxylate ligators at the Ru2 paddle-wheels. Incorporation of pyridine-3,5-dicarboxylate (pydc), which is the same size as btc but carries lower charge, as a second, defective linker has led to the mixed-linker isoreticular derivatives of Ru-MOF, which display characteristics unlike those of the defect-free framework. Along with the creation of additional coordinatively unsaturated sites, the incorporation of pydc induces the partial reduction of ruthenium. Accordingly, the modified Ru sites are responsible for the activity of the "defective" variants in the dissociative chemisorption of CO 2, the enhanced performance in CO sorption, the formation of hydride species, and the catalytic hydrogenation of olefins. The defect engineering in Ru-based metal-organic frameworks (MOFs) at coordinatively unsaturated metal centers (CUS) induces partial reduction of the metal nodes and leads to properties that are absent for the parent MOF, such as dissociative chemisorption of CO2 and enhanced sorption capacity of CO. The modified MOFs offer new perspectives as multifunctional materials whose performance is controlled by design of the defects. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201311128
  • 2014 • 296 Influence of storage condition on properties of MCC II-based pellets with theophylline-monohydrate
    Krueger, C. and Thommes, M. and Kleinebudde, P.
    European Journal of Pharmaceutics and Biopharmaceutics 88 483-491 (2014)
    Microcrystalline cellulose II (MCC II1) is a polymorph of commonly used MCC I; in 2010 it was introduced as new pelletization aid in wet-extrusion/spheronization leading to fast disintegrating pellets. Previous investigations suggested that the storage of the resulting pellets affect the disintegration behavior, the non-hygroscopic substance chloramphenicol that showed no polymorphism or hydrate formation due to relative humidity was used for the investigations. Therefore, theophylline-monohydrate that can dehydrate during storage, but also during manufacturing and drying was used for this study to confirm the results of the previous study and give a more detailed overview of the influence of recrystallization of theophylline monohydrate on disintegration. Storage recommendations should be derived. MCC II-based pellets were prepared of binary mixtures containing 10%, 20% or 50% MCC II as pelletization aid and theophylline-monohydrate as API. These pellets were stored at different relative humidity (0-97%rH; 20 °C); the influence on their disintegration and drug release was investigated. The storage conditions had an impact on pellet disintegration. Low relative humidities (≤40%rH) led to a conversion of the monohydrate to the anhydrous form. Newly grown crystals formed a kind of network around the pellet and inhibited the disintegration. High relative humidity (>80%rh) affected the disintegration caused by changes in the MCC II as already seen in the previous study. Due to the changed disintegration behavior also the drug release and release kinetic changed. Therefore, for theophylline containing pellets a storage humidity of 55%rH to 80%rH (20 °C) is recommended. All in all, these investigations substantiate the knowledge of MCC II-based pellets providing a better basis for adequate storage conditions of MCC II based pellets. © 2014 Elsevier B.V. All rights reserved.
    view abstractdoi: 10.1016/j.ejpb.2014.06.006
  • 2014 • 295 Perfluorodecalin-soluble fluorescent dyes for the monitoring of circulating nanocapsules with intravital fluorescence microscopy
    Laudien, J. and Naglav, D. and Groß-Heitfeld, C. and Ferenz, K.B. and De Groot, H. and Mayer, C. and Schulz, S. and Schnepf, A. and Kirsch, M.
    Journal of Microencapsulation 31 738-745 (2014)
    Perfluorodecalin (PFD) is an established artificial oxygen carrier due to its physical capability to solve the respiratory gases oxygen and carbon dioxide. PFD-filled poly(n-butyl-cyanoacrylate) (PACA) nanocapsules are already discussed as effective artificial oxygen carriers, and their principal suitability for intravenous administration had been shown. To further elucidate their action in vivo, it is imperative to characterise their preclinical safety and particularly their biodistribution. For these purposes, intravital fluorescence microscopy would display an attractive technique in order to monitor the PACA nanocapsules in vivo, but unfortunately, it is impossible to stain the PACA nanocapsules with a fluorescent dye fulfilling special criteria required for in vivo microscopy. In order to develop such a dye, a long-chained fluorinated thiol was used to modify a BODIPY derivative that is a highly fluorescent organic compound belonging to the difluoro-boraindacene family, as well as to functionalise mesoscopic systems, such as CdSe/ZnS-quantum dots and gold nanoparticles. Furthermore, a functionalisation of porphyrin derivatives was investigated by placing divalent ions in the centre of these systems. Due to the high solubility of all synthesised dyes in PFD, it should be possible to stain PFD-filled particles in general. However, only the functionalised BODIPY derivative was suitable for in vivo monitoring of the PFD-filled PACA nanocapsules. © 2014 Informa UK Ltd.
    view abstractdoi: 10.3109/02652048.2014.918668
  • 2014 • 294 Hot-melt extruded drug-loaded rods: Evaluation of the mechanical properties for individual dosing via the Solid Dosage Pen
    Laukamp, E.J. and Thommes, M. and Breitkreutz, J.
    International Journal of Pharmaceutics 475 344-350 (2014)
    Individual dosing of peroral medicines is important for personalised medicine and patient-centred treatment, e.g., of children and the elderly. The Solid Dosage Pen (SDP) offers the opportunity to dose individually by cutting drug-loaded rods into tablet-like slices. The aim of the present study is the systematic evaluation of the mechanical properties of these drug-loaded rods prepared via hot-melt extrusion. The drug-loaded rods contain carbamazepine as a model drug, and polyethylene glycols and poloxamers as excipients. For the evaluation of the mechanical properties of the extrudates, three parameters were considered: tensile strength, E-modulus, and maximum cutting force. To examine the practicability of the device and the formulations for patient-centred treatment, the needed cutting forces were compared to literature data of the manual forces of different age groups. The maximum cutting force and the tensile strength were marginally changed over a storage period of six months (21 ± 0.2 °C, 45% r.H). A tensile strength below 9.1 ± 0.3 MPa and an E-modulus below 135.9 ± 7.2 MPa were found to be valuable thresholds for the applicability by the Solid Dosage Pen. Formulations containing PEG 1500 as additive fulfilled the pharmacopeial requirements containing the content uniformity even for the smallest dose. © 2014 Elsevier B.V. All rights reserved.
    view abstractdoi: 10.1016/j.ijpharm.2014.09.001
  • 2014 • 293 Hidden structural features of multicompartment micelles revealed by cryogenic transmission electron tomography
    Löbling, T.I. and Haataja, J.S. and Synatschke, C.V. and Schacher, F.H. and Müller, M. and Hanisch, A. and Gröschel, A.H. and Müller, A.H.E.
    ACS Nano 8 11330-11340 (2014)
    The demand for ever more complex nanostructures in materials and soft matter nanoscience also requires sophisticated characterization tools for reliable visualization and interpretation of internal morphological features. Here, we address both aspects and present synthetic concepts for the compartmentalization of nanoparticle peripheries as well as their in situ tomographic characterization. We first form negatively charged spherical multicompartment micelles from ampholytic triblock terpolymers in aqueous media, followed by interpolyelectrolyte complex (IPEC) formation of the anionic corona with bis-hydrophilic cationic/neutral diblock copolymers. At a 1:1 stoichiometric ratio of anionic and cationic charges, the so-formed IPECs are charge neutral and thus phase separate from solution (water). The high chain density of the ionic grafts provides steric stabilization through the neutral PEO corona of the grafted diblock copolymer and suppresses collapse of the IPEC; instead, the dense grafting results in defined nanodomains oriented perpendicular to the micellar core. We analyze the 3D arrangements of the complex and purely organic compartments, in situ, by means of cryogenic transmission electron microscopy (cryo-TEM) and tomography (cryo-ET). We study the effect of block lengths of the cationic and nonionic block on IPEC morphology, and while 2D cryo-TEM projections suggest similar morphologies, cryo-ET and computational 3D reconstruction reveal otherwise hidden structural features, e.g., planar IPEC brushes emanating from the micellar core. (Figure Presented). © 2014 American Chemical Society.
    view abstractdoi: 10.1021/nn504197y
  • 2014 • 292 Versatile reactivity of a solvent-coordinated diiron(II) compound: Synthesis and dioxygen reactivity of a mixed-valent FeIIFe III species
    Majumdar, A. and Apfel, U.-P. and Jiang, Y. and Moënne-Loccoz, P. and Lippard, S.J.
    Inorganic Chemistry 53 167-181 (2014)
    A new, DMF-coordinated, preorganized diiron compound [Fe 2(N-Et-HPTB)(DMF)4](BF4)3 (1) was synthesized, avoiding the formation of [Fe(N-Et-HPTB)](BF4) 2 (10) and [Fe2(N-Et-HPTB)(μ-MeCONH)](BF 4)2 (11), where N-Et-HPTB is the anion of N,N,N′,N′-tetrakis[2-(1-ethylbenzimidazolyl)]-2-hydroxy-1, 3-diaminopropane. Compound 1 is a versatile reactant from which nine new compounds have been generated. Transformations include solvent exchange to yield [Fe2(N-Et-HPTB)(MeCN)4](BF4)3 (2), substitution to afford [Fe2(N-Et-HPTB)(μ-RCOO)](BF 4)2 (3, R = Ph; 4, RCOO = 4-methyl-2,6-diphenyl benzoate]), one-electron oxidation by (Cp2Fe)(BF4) to yield a Robin-Day class II mixed-valent diiron(II,III) compound, [Fe 2(N-Et-HPTB)(μ-PhCOO)(DMF)2](BF4) 3 (5), two-electron oxidation with tris(4-bromophenyl)aminium hexachloroantimonate to generate [Fe2(N-Et-HPTB)Cl 3(DMF)](BF4)2 (6), reaction with (2,2,6,6-tetramethylpiperidin-1-yl)oxyl to form [Fe5(N-Et-HPTB) 2(μ-OH)4(μ-O)(DMF)2](BF4) 4 (7), and reaction with dioxygen to yield an unstable peroxo compound that decomposes at room temperature to generate [Fe4(N-Et- HPTB)2(μ-O)3(H2O)2](BF 4)·8DMF (8) and [Fe4(N-Et-HPTB)2(μ-O) 4](BF4)2 (9). Compound 5 loses its bridging benzoate ligand upon further oxidation to form [Fe2(N-Et-HPTB)(OH) 2(DMF)2](BF4)3 (12). Reaction of the diiron(II,III) compound 5 with dioxygen was studied in detail by spectroscopic methods. All compounds (1-12) were characterized by single-crystal X-ray structure determinations. Selected compounds and reaction intermediates were further examined by a combination of elemental analysis, electronic absorption spectroscopy, Mössbauer spectroscopy, EPR spectroscopy, resonance Raman spectroscopy, and cyclic voltammetry. © 2013 American Chemical Society.
    view abstractdoi: 10.1021/ic4019585
  • 2014 • 291 Effects of bleaching agents on surface roughness of filling materials
    Markovic, L. and Jordan, R.A. and Glasser, M.-C. and Arnold, W.H. and Nebel, J. and Tillmann, W. and Ostermann, T. and Zimmer, S.
    Dental Materials Journal 33 59-63 (2014)
    The aim of this study was to use a non-tactile optical measurement system to assess the effects of three bleaching agents' concentrations on the surface roughness of dental restoration materials. Two composites (Grandio, Venus) and one glass ionomer cement (Ketac Fil Plus) were used in this in vitro study. Specimens were treated with three different bleaching agents (16% and 22% carbamide peroxide (Polanight) and 38% hydrogen peroxide (Opalescence Boost)). Surface roughness was measured with an optical profilometer (Infinite Focus G3) before and after the bleaching treatment. Surface roughness increased in all tested specimens after bleaching treatment (p<0.05). Our in vitro study showed that dental bleaching agents influenced the surface roughness of different restoration materials, and the restoration material itself was shown to have an impact on alteration susceptibility. There seemed to be no clinical relevance in case of an optimal finish.
    view abstractdoi: 10.4012/dmj.2012-217
  • 2014 • 290 In situ non-DLVO stabilization of surfactant-free, plasmonic gold nanoparticles: Effect of Hofmeister's anions
    Merk, V. and Rehbock, C. and Becker, F. and Hagemann, U. and Nienhaus, H. and Barcikowski, S.
    Langmuir 30 4213-4222 (2014)
    Specific ion effects ranking in the Hofmeister sequence are ubiquitous in biochemical, industrial, and atmospheric processes. In this experimental study specific ion effects inexplicable by the classical DLVO theory have been investigated at curved water-metal interfaces of gold nanoparticles synthesized by a laser ablation process in liquid in the absence of any organic stabilizers. Notably, ion-specific differences in colloidal stability occurred in the Hückel regime at extraordinarily low salinities below 50 μM, and indications of a direct influence of ion-specific effects on the nanoparticle formation process are found. UV-vis, zeta potential, and XPS measurements help to elucidate coagulation properties, electrokinetic potential, and the oxidation state of pristine gold nanoparticles. The results clearly demonstrate that stabilization of ligand-free gold nanoparticles scales proportionally with polarizability and antiproportionally with hydration of anions located at defined positions in a direct Hofmeister sequence of anions. These specific ion effects might be due to the adsorption of chaotropic anions (Br-, SCN-, or I-) at the gold/water interface, leading to repulsive interactions between the partially oxidized gold particles during the nanoparticle formation process. On the other hand, kosmotropic anions (F - or SO4 2-) seem to destabilize the gold colloid, whereas Cl- and NO3 - give rise to an intermediate stability. Quantification of surface charge density indicated that particle stabilization is dominated by ion adsorption and not by surface oxidation. Fundamental insights into specific ion effects on ligand-free aqueous gold nanoparticles beyond purely electrostatic interactions are of paramount importance in biomedical or catalytic applications, since colloidal stability appears to depend greatly on the type of salt rather than on the amount. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/la404556a
  • 2014 • 289 Oxidation of bioethanol using zeolite-encapsulated gold nanoparticles
    Mielby, J. and Abildstrøm, J.O. and Wang, F. and Kasama, T. and Weidenthaler, C. and Kegnæs, S.
    Angewandte Chemie - International Edition 53 12513-12516 (2014)
    With the ongoing developments in biomass conversion, the oxidation of bioethanol to acetaldehyde may become a favorable and green alternative to the preparation from ethylene. Here, a simple and effective method to encapsulate gold nanoparticles in zeolite silicalite-1 is reported and their high activity and selectivity for the catalytic gas-phase oxidation of ethanol are demonstrated. The zeolites are modified by a recrystallization process, which creates intraparticle voids and mesopores that facilitate the formation of small and disperse nanoparticles upon simple impregnation. The individual zeolite crystals comprise a broad range of mesopores and contain up to several hundred gold nanoparticles with a diameter of 2-3 nm that are distributed inside the zeolites rather than on the outer surface. The encapsulated nanoparticles have good stability and result in 50%conversion of ethanol with 98% selectivity toward acetaldehyde at 200°C, which (under the given reaction conditions) corresponds to 606 mol acetaldehyde/mol Au hour-1. © 2014 Wiley-VCH Verlag GmbH & Co. KGaA Weinheim.
    view abstractdoi: 10.1002/anie.201406354
  • 2014 • 288 Specific anion effects on the pressure dependence of the protein-protein interaction potential
    Möller, J. and Grobelny, S. and Schulze, J. and Steffen, A. and Bieder, S. and Paulus, M. and Tolan, M. and Winter, R.
    Physical Chemistry Chemical Physics 16 7423-7429 (2014)
    We present a study on ion specific effects on the intermolecular interaction potential V(r) of dense protein solutions under high hydrostatic pressure conditions. Small-angle X-ray scattering in combination with a liquid-state theoretical approach was used to determine the effect of structure breaking/making salt anions (Cl-, SO4 2-, PO4 3-) on the intermolecular interaction of lysozyme molecules. It was found that besides the Debye-Hückel charge screening effect, reducing the repulsiveness of the interaction potential V(r) at low salt concentrations, a specific ion effect is observed at high salt concentrations for the multivalent kosmotropic anions, which modulates also the pressure dependence of the protein-protein interaction potential. Whereas sulfate and phosphate strongly influence the pressure dependence of V(r), chloride anions do not. The strong structure-making effect of the multivalent anions, dominating for the triply charged PO4 3-, renders the solution structure less bulk-water-like at high salt concentrations, which leads to an altered behavior of the pressure dependence of V(r). Hence, the particular structural properties of the salt solutions are able to influence the spatial organization and the intermolecular interactions of the proteins, in particular upon compression. These results are of interest for exploring the combined effects of ionic strength, temperature and pressure on the phase behavior of protein solutions, but may also be of relevance for understanding pressure effects on the hydration behavior of biological matter under extreme environmental conditions. This journal is © the Partner Organisations 2014.
    view abstractdoi: 10.1039/c3cp55278k
  • 2014 • 287 Reentrant liquid-liquid phase separation in protein solutions at elevated hydrostatic pressures
    Möller, J. and Grobelny, S. and Schulze, J. and Bieder, S. and Steffen, A. and Erlkamp, M. and Paulus, M. and Tolan, M. and Winter, R.
    Physical Review Letters 112 (2014)
    We present results from small-angle x-ray scattering data on the effect of high pressure on the phase behavior of dense lysozyme solutions in the liquid-liquid phase separation region, and characterize the underlying intermolecular protein-protein interactions as a function of temperature and pressure in this region of phase space. A reentrant liquid-liquid phase separation region has been discovered at elevated pressures, which originates in the pressure dependence of the solvent-mediated protein-protein interactions. © 2014 American Physical Society.
    view abstractdoi: 10.1103/PhysRevLett.112.028101
  • 2014 • 286 Small-scale twin-screw extrusion - evaluation of continuous split feeding
    Muehlenfeld, C. and Thommes, M.
    The Journal of pharmacy and pharmacology 66 1667-1676 (2014)
    OBJECTIVES: The aim of this work was to evaluate a continuous, small-scale extrusion process with a particular focus on powder and liquid-feeding systems, because it is likely that uniformity issues are related to small-scale production. METHODS: The study is divided into three parts. The first part investigates the uniformity and accuracy of the powder and the liquid feeders. In the second part, a solid polymer and low amounts of liquid plasticizer were combined in hot-melt extrusion. The third part deals with wet extrusion-spheronization using water as the granulation liquid. KEY FINDINGS: The powder and the liquid feed rate were identified as crucial parameters in small-scale extrusion. With respect to powder feeding, the cohesiveness of the powder and electrostatic charging are the limitations, while liquid feeding is challenging based on particularly low feed rates. The hot-melt extrusion was performed using a powder feed rate of 2 g/min. When small quantities of plasticizer were applied to the hot melt extrusions (from 2.5% to 15% w/w), homogenous plasticizer distribution was found. In wet extrusion, larger quantities of water were used and the extrudates were investigated with respect to their spheronization behaviour. Spherical pellets were obtained at certain water contents. CONCLUSIONS: These findings demonstrated that the extruder is a useful tool to screen formulations and perform feasibility studies on a small scale in the early stages of product development. © 2014 Royal Pharmaceutical Society.
    view abstractdoi: 10.1111/jphp.12301
  • 2014 • 285 Effects of microtubule mechanics on hydrolysis and catastrophes
    Müller, N. and Kierfeld, J.
    Physical Biology 11 (2014)
    We introduce a model for microtubule (MT) mechanics containing lateral bonds between dimmers in neighboring protofilaments, bending rigidity of dimers, and repulsive interactions between protofilaments modeling steric constraints to investigate the influence of mechanical forces on hydrolysis and catastrophes. We use the allosteric dimer model, where tubulin dimers are characterized by an equilibrium bending angle, which changes from 0°to 22°by hydrolysis of a dimer. This also affects the lateral interaction and bending energies and, thus, the mechanical equilibrium state of the MT. As hydrolysis gives rise to conformational changes in dimers, mechanical forces also influence the hydrolysis rates by mechanical energy changes modulating the hydrolysis rate. The interaction via the MT mechanics then gives rise to correlation effects in the hydrolysis dynamics, which have not been taken into account before. Assuming a dominant influence of mechanical energies on hydrolysis rates, we investigate the most probable hydrolysis pathways both for vectorial and random hydrolysis. Investigating the stability with respect to lateral bond rupture, we identify initiation configurations for catastrophes along the hydrolysis pathways and values for a lateral bond rupture force. If we allow for rupturing of lateral bonds between dimers in neighboring protofilaments above this threshold force, our model exhibits avalanche-like catastrophe events. © 2014 IOP Publishing Ltd Printed in the UK.
    view abstractdoi: 10.1088/1478-3975/11/4/046001
  • 2014 • 284 Interaction of colloidal nanoparticles with their local environment: The (ionic) nanoenvironment around nanoparticles is different from bulk and determines the physico-chemical properties of the nanoparticles
    Pfeiffer, C. and Rehbock, C. and Hühn, D. and Carrillo-Carrion, C. and De Aberasturi, D.J. and Merk, V. and Barcikowski, S. and Parak, W.J.
    Journal of the Royal Society Interface 11 (2014)
    The physico-chemical properties of colloidal nanoparticles (NPs) are influenced by their local environment, as, in turn, the local environment influences the physico-chemical properties of the NPs. In other words, the local environment around NPs has a profound impact on the NPs, and it is different from bulk due to interaction with the NP surface. So far, this important effect has not been addressed in a comprehensive way in the literature. The vicinity of NPs can be sensitively influenced by local ions and ligands, with effects already occurring at extremely low concentrations. NPs in the Hückel regime are more sensitive to fluctuations in the ionic environment, because of a larger Debye length. The local ion concentration hereby affects the colloidal stability of the NPs, as it is different from bulk owing to Debye Hückel screening caused by the charge of the NPs. This can have subtle effects, now caused by the environment to the performance of the NP, such as for example a buffering effect caused by surface reaction on ultrapure ligandfree nanogold, a size quenching effect in the presence of specific ions and a significant impact on fluorophore-labelled NPs acting as ion sensors. Thus, the aim of this review is to clarify and give an unifying view of the complex interplay between the NP's surface with their nanoenvironment. © 2014 The Author(s) Published by the Royal Society. All rights reserved.
    view abstractdoi: 10.1098/rsif.2013.0931
  • 2014 • 283 A redox hydrogel protects hydrogenase from high-potential deactivation and oxygen damage
    Plumeré, N. and Rüdiger, O. and Oughli, A.A. and Williams, R. and Vivekananthan, J. and Pöller, S. and Schuhmann, W. and Lubitz, W.
    Nature Chemistry 6 822-827 (2014)
    Hydrogenases are nature's efficient catalysts for both the generation of energy via oxidation of molecular hydrogen and the production of hydrogen via the reduction of protons. However, their O2 sensitivity and deactivation at high potential limit their applications in practical devices, such as fuel cells. Here, we show that the integration of an O2 -sensitive hydrogenase into a specifically designed viologen-based redox polymer protects the enzyme from O2 damage and high-potential deactivation. Electron transfer between the polymer-bound viologen moieties controls the potential applied to the active site of the hydrogenase and thus insulates the enzyme from excessive oxidative stress. Under catalytic turnover, electrons provided from the hydrogen oxidation reaction induce viologen-catalysed O 2 reduction at the polymer surface, thus providing self-activated protection from O2. The advantages of this tandem protection are demonstrated using a single-compartment biofuel cell based on an O2 -sensitive hydrogenase and H2/O2 mixed feed under anode-limiting conditions.
    view abstractdoi: 10.1038/nchem.2022
  • 2014 • 282 Thermodynamic phase behavior of API/polymer solid dispersions
    Prudic, A. and Ji, Y. and Sadowski, G.
    Molecular Pharmaceutics 11 2294-2304 (2014)
    To improve the bioavailability of poorly soluble active pharmaceutical ingredients (APIs), these materials are often integrated into a polymer matrix that acts as a carrier. The resulting mixture is called a solid dispersion. In this work, the phase behaviors of solid dispersions were investigated as a function of the API as well as of the type and molecular weight of the carrier polymer. Specifically, the solubility of artemisinin and indomethacin was measured in different poly(ethylene glycol)s (PEG 400, PEG 6000, and PEG 35000). The measured solubility data and the solubility of sulfonamides in poly(vinylpyrrolidone) (PVP) K10 and PEG 35000 were modeled using the perturbed-chain statistical associating fluid theory (PC-SAFT). The results show that PC-SAFT predictions are in a good accordance with the experimental data, and PC-SAFT can be used to predict the whole phase diagram of an API/polymer solid dispersion as a function of the kind of API and polymer and of the polymers molecular weight. This remarkably simplifies the screening process for suitable API/polymer combinations. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/mp400729x
  • 2014 • 281 Influence of copolymer composition on the phase behavior of solid dispersions
    Prudic, A. and Kleetz, T. and Korf, M. and Ji, Y. and Sadowski, G.
    Molecular Pharmaceutics 11 4189-4198 (2014)
    The incorporation of poorly soluble active pharmaceutical ingredients (APIs) into excipients (e.g., polymers) to formulate an amorphous solid dispersion is a promising strategy to improve the oral bioavailability of the API. The application of copolymer excipients allows access to combinations of different monomers and thus to the design of excipients to improve solid-dispersion properties. In this work, the thermodynamic phase behavior of solid dispersions was investigated as a function of the API, type of monomer, and copolymer composition. The glass-transition temperatures and API solubilities in the solid dispersions of naproxen and indomethacin in polyvinylpyrrolidone, polyvinyl acetate, and copolymers with different weight fractions of vinylpyrrolidone and vinyl actetate were investigated. It is shown that the thermodynamic phase behavior of API/copolymer solid dispersions is a function of monomer type and copolymer composition. This effect was also predicted by using the perturbed-chain statistical associating fluid theory (PC-SAFT). The glass-transition temperature of the solid dispersions was calculated with the Gordon-Taylor equation. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/mp500412d
  • 2014 • 280 Swimming by reciprocal motion at low Reynolds number
    Qiu, T. and Lee, T.-C. and Mark, A.G. and Morozov, K.I. and Münster, R. and Mierka, O. and Turek, S. and Leshansky, A.M. and Fischer, P.
    Nature Communications 5 (2014)
    Biological microorganisms swim with flagella and cilia that execute nonreciprocal motions for low Reynolds number (Re) propulsion in viscous fluids. This symmetry requirement is a consequence of Purcell' s scallop theorem, which complicates the actuation scheme needed by microswimmers. However, most biomedically important fluids are non-Newtonian where the scallop theorem no longer holds. It should therefore be possible to realize a microswimmer that moves with reciprocal periodic body-shape changes in non-Newtonian fluids. Here we report a symmetric 'micro-scallop', a single-hinge microswimmer that can propel in shear thickening and shear thinning (non-Newtonian) fluids by reciprocal motion at low Re. Excellent agreement between our measurements and both numerical and analytical theoretical predictions indicates that the net propulsion is caused by modulation of the fluid viscosity upon varying the shear rate. This reciprocal swimming mechanism opens new possibilities in designing biomedical microdevices that can propel by a simple actuation scheme in non-Newtonian biological fluids.
    view abstractdoi: 10.1038/ncomms6119
  • 2014 • 279 A special thematic compilation/special issue crossover with biochemistry, journal of medicinal chemistry, and ACS medicinal chemistry letters focused on kinases
    Rauh, D.
    ACS Chemical Biology 9 579-580 (2014)
    doi: 10.1021/cb500150d
  • 2014 • 278 Urease-induced calcification of segmented polymer hydrogels - A step towards artificial biomineralization
    Rauner, N. and Meuris, M. and Dech, S. and Godde, J. and Tiller, J.C.
    Acta Biomaterialia 10 3942-3951 (2014)
    Natural organic/inorganic composites, such as nacre, bones and teeth, are perfectly designed materials with exceptional mechanical properties. Numerous approaches have been taken to synthetically prepare such composites. The presented work describes a new way of mineralizing bulk materials on a large scale following the approach of bioinduced mineralization. To this end, a series of polymer conetworks with entrapped urease were prepared. After polymerization, the entrapped urease shows high enzymatic activity. The bioactive polymer conetworks were then treated with an aqueous mixture of urea and CaCl2. The urease-induced calcification indeed allows formation of carbonate crystals exclusively within the hydrogel even at room temperature. The influence of network composition, degree of cross-linking, immobilized urease concentration and temperature of calcification were investigated. By varying these parameters, spherical, monolithic clusters, as well as bar-like nanocrystals with different aspect ratios in spherical or dendritic arrays, are formed. The grown nanocrystals improve the stiffness of the starting material by up to 700-fold, provided that the microstructure shows a dense construction without pores and strong interaction between crystals and network. The process has the potential to generate a new class of hybrid materials that would be available on the macroscopic scale for use in lightweight design and medicine. © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
    view abstractdoi: 10.1016/j.actbio.2014.05.021
  • 2014 • 277 Nucleic acids nanotechnology
    Saccà, B.
    Methods 67 103-104 (2014)
    doi: 10.1016/j.ymeth.2014.04.018
  • 2014 • 276 Two-color SERS microscopy for protein co-localization in prostate tissue with primary antibody-protein A/G-gold nanocluster conjugates
    Salehi, M. and Schneider, L. and Ströbel, P. and Marx, A. and Packeisen, J. and Schlücker, S.
    Nanoscale 6 2361-2367 (2014)
    SERS microscopy is a novel staining technique in immunohistochemistry, which is based on antibodies labeled with functionalized noble metal colloids called SERS labels or nanotags for optical detection. Conventional covalent bioconjugation of these SERS labels cannot prevent blocking of the antigen recognition sites of the antibody. We present a rational chemical design for SERS label-antibody conjugates which addresses this issue. Highly sensitive, silica-coated gold nanoparticle clusters as SERS labels are non-covalently conjugated to primary antibodies by using the chimeric protein A/G, which selectively recognizes the Fc part of antibodies and therefore prevents blocking of the antigen recognition sites. In proof-of-concept two-color imaging experiments for the co-localization of p63 and PSA on non-neoplastic prostate tissue FFPE specimens, we demonstrate the specificity and signal brightness of these rationally designed primary antibody-protein A/G-gold nanocluster conjugates. © 2014 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c3nr05890e
  • 2014 • 275 3D-electrode architectures for enhanced direct bioelectrocatalysis of pyrroloquinoline quinone-dependent glucose dehydrogenase
    Sarauli, D. and Peters, K. and Xu, C. and Schulz, B. and Fattakhova-Rohlfing, D. and Lisdat, F.
    ACS Applied Materials and Interfaces 6 17887-17893 (2014)
    We report on the fabrication of a complex electrode architecture for efficient direct bioelectrocatalysis. In the developed procedure, the redox enzyme pyrroloquinoline quinone-dependent glucose dehydrogenase entrapped in a sulfonated polyaniline [poly(2-methoxyaniline-5-sulfonic acid)-co-aniline] was immobilized on macroporous indium tin oxide (macroITO) electrodes. The use of the 3D-conducting scaffold with a large surface area in combination with the conductive polymer enables immobilization of large amounts of enzyme and its efficient communication with the electrode, leading to enhanced direct bioelectrocatalysis. In the presence of glucose, the fabricated bioelectrodes show an exceptionally high direct bioelectrocatalytical response without any additional mediator. The catalytic current is increased more than 200-fold compared to planar ITO electrodes. Together with a high long-term stability (the current response is maintained for >90% of the initial value even after 2 weeks of storage), the transparent 3D macroITO structure with a conductive polymer represents a valuable basis for the construction of highly efficient bioelectronic units, which are useful as indicators for processes liberating glucose and allowing optical and electrochemical transduction. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/am5046026
  • 2014 • 274 Immobilization of proteins in their physiological active state at functionalized thiol monolayers on ATR-germanium crystals
    Schartner, J. and Gavriljuk, K. and Nabers, A. and Weide, P. and Muhler, M. and Gerwert, K. and Kötting, C.
    ChemBioChem 15 2529-2534 (2014)
    Protein immobilization on solid surfaces has become a powerful tool for the investigation of protein function. Physiologically relevant molecular reaction mechanisms and interactions of proteins can be revealed with excellent signal-to-noise ratio by vibrational spectroscopy (ATR-FTIR) on germanium crystals. Protein immobilization by thiol chemistry is well-established on gold surfaces, for example, for surface plasmon resonance. Here, we combine features of both approaches: a germanium surface functionalized with different thiols to allow specific immobilization of various histidine-tagged proteins with over 99% specific binding. In addition to FTIR, the surfaces were characterized by XPS and fluorescence microscopy. Secondary-structure analysis and stimulus-induced difference spectroscopy confirmed protein activity at the atomic level, for example, physiological cation channel formation of Channelrhodopsin 2. © 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cbic.201402478
  • 2014 • 273 Targeted manipulation of metal-organic frameworks to direct sorption properties
    Schneemann, A. and Henke, S. and Schwedler, I. and Fischer, R.A.
    ChemPhysChem 15 823-839 (2014)
    Metal-organic frameworks are promising materials for manifold applications. This Minireview highlights approaches for the fine-tuning of specific sorption properties (e.g. capacity, selectivity, and breathing behavior) of this interesting class of materials. Central aspects covered are the control over the crystal morphology, the targeted tuning of sorption properties by judicious choice of metal centers and linkers, and the preparation of host-guest systems. We want to introduce the reader to these topics on the basis of the manipulation of a handful of outstanding prototypical metal-organic frameworks. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cphc.201300976
  • 2014 • 272 Photothermal laser fabrication of micro- and nanostructured chemical templates for directed protein immobilization
    Schröter, A. and Franzka, S. and Hartmann, N.
    Langmuir 30 14841-14848 (2014)
    Photothermal patterning of poly(ethylene glycol) terminated organic monolayers on surface-oxidized silicon substrates is carried out using a microfocused beam of a CW laser operated at a wavelength of 532 nm. Trichlorosilane and trimethoxysilane precursors are used for coating. Monolayers from trimethoxysilane precursors show negligible unspecific protein adsorption in the background, i.e., provide platforms of superior protein repellency. Laser patterning results in decomposition of the monolayers and yields chemical templates for directed immobilization of proteins at predefined positions. Characterization is carried out via complementary analytical methods including fluorescence microscopy, atomic force microscopy, and scanning electron microscopy. Appropriate labeling techniques (fluorescent markers and gold clusters) and substrates (native and thermally oxidized silicon substrates) are chosen in order to facilitate identification of protein adsorption and ensure high sensitivity and selectivity. Variation of the laser parameters at a 1/e2 spot diameter of 2.8 μm allows for fabrication of protein binding domains with diameters on the micrometer and nanometer length scale. Minimum domain sizes are about 300 nm. In addition to unspecific protein adsorption on as-patterned monolayers, biotin-streptavidin coupling chemistry is exploited for specific protein binding. This approach represents a novel facile laser-based means for fabrication of protein micro- and nanopatterns. The routine is readily applicable to femtosecond laser processing of glass substrates for the fabrication of transparent templates. (Graph Presented). © 2014 American Chemical Society.
    view abstractdoi: 10.1021/la503814n
  • 2014 • 271 One-step synthesis of bismuth molybdate catalysts via flame spray pyrolysis for the selective oxidation of propylene to acrolein
    Schuh, K. and Kleist, W. and Høj, M. and Trouillet, V. and Jensen, A.D. and Grunwaldt, J.-D.
    Chemical Communications 50 15404-15406 (2014)
    Flame spray pyrolysis (FSP) of Bi(iii)- and Mo(vi)-2-ethylhexanoate dissolved in xylene resulted in various nanocrystalline bismuth molybdate phases depending on the Bi/Mo ratio. Besides α-Bi2Mo3O12 and γ-Bi2MoO6, FSP gave direct access to the metastable β-Bi2Mo2O9 phase with high surface area (19 m2 g-1). This phase is normally only obtained at high calcination temperatures (&gt;560 °C) resulting in lower surface areas. The β-phase was stable up to 400 °C and showed superior catalytic performance compared to α- and γ-phases in selective oxidation of propylene to acrolein at temperatures relevant for industrial applications (360 °C). This journal is © The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c4cc07527g
  • 2014 • 270 Liquid 1-propanol studied by neutron scattering, near-infrared, and dielectric spectroscopy
    Sillrén, P. and Matic, A. and Karlsson, M. and Koza, M. and MacCarini, M. and Fouquet, P. and Götz, M. and Bauer, T. and Gulich, R. and Lunkenheimer, P. and Loidl, A. and Mattsson, J. and Gainaru, C. and Vynokur, E. and Schildma...
    Journal of Chemical Physics 140 (2014)
    Liquid monohydroxy alcohols exhibit unusual dynamics related to their hydrogen bonding induced structures. The connection between structure and dynamics is studied for liquid 1-propanol using quasi-elastic neutron scattering, combining time-of-flight and neutron spin-echo techniques, with a focus on the dynamics at length scales corresponding to the main peak and the pre-peak of the structure factor. At the main peak, the structural relaxation times are probed. These correspond well to mechanical relaxation times calculated from literature data. At the pre-peak, corresponding to length scales related to H-bonded structures, the relaxation times are almost an order of magnitude longer. According to previous work [C. Gainaru, R. Meier, S. Schildmann, C. Lederle, W. Hiller, E. Rössler, and R. Böhmer, Phys. Rev. Lett. 105, 258303 (2010)] this time scale difference is connected to the average size of H-bonded clusters. The relation between the relaxation times from neutron scattering and those determined from dielectric spectroscopy is discussed on the basis of broad-band permittivity data of 1-propanol. Moreover, in 1-propanol the dielectric relaxation strength as well as the near-infrared absorbance reveal anomalous behavior below ambient temperature. A corresponding feature could not be found in the polyalcohols propylene glycol and glycerol. © 2014 AIP Publishing LLC.
    view abstractdoi: 10.1063/1.4868556
  • 2014 • 269 FLiK: A direct-binding assay for the identification and kinetic characterization of stabilizers of inactive kinase conformations
    Simard, J.R. and Rauh, D.
    Methods in Enzymology 548 147-171 (2014)
    Despite the hundreds of kinase inhibitors currently in discovery and preclinical phases, the number of FDA-approved kinase inhibitors remains very low by comparison, a discrepancy which reflects the challenges which accompanies kinase inhibitor development. Targeting protein kinases with ATP-competitive inhibitors has been the classical approach to inhibit kinase activity, but the highly conserved nature of the ATP-binding site often contributes to the poor inhibitor selectivity. To address this problem, we developed a high-throughput screening technology that can discriminate for inhibitors, which stabilize inactive kinase conformations by binding within allosteric pockets in the kinase domain. Here, we describe how to use the Fluorescence Labels in Kinases approach to measure the Kd of ligands as well as how to kinetically characterize the binding and dissociation of ligands to the kinase. We also describe how this technology can be used to rapidly screen small molecule libraries in high throughput. © 2014 Elsevier Inc. All rights reserved.
    view abstractdoi: 10.1016/B978-0-12-397918-6.00006-9
  • 2014 • 268 D-lactate-selective amperometric biosensor based on the cell debris of the recombinant yeast Hansenula polymorpha
    Smutok, O.V. and Dmytruk, K.V. and Karkovska, M.I. and Schuhmann, W. and Gonchar, M.V. and Sibirny, A.A.
    Talanta 125 227-232 (2014)
    A d-lactate-selective biosensor has been developed using cellsdebris of recombinant thermotolerant methylotrophic yeast Hansenula polymorpha, overproducing d-lactate: cytochrome c-oxidoreductase (EC 1.1.2.4, d-lactate dehydrogenase (cytochrome), DlDH). The H. polymorpha DlDH-producer was constructed in two steps. First, the gene CYB2 was deleted on the background of the C-105 (gcr1 catX) strain of H. polymorpha impaired in glucose repression and devoid of catalase activity to avoid specific l-lactate-cytochrome c oxidoreductase activity. Second, the homologous gene DLD1 coding for DlDH was overexpressed under the control of the strong H. polymorpha alcohol oxidase promoter in the frame of a plasmid for multicopy integration in the Δcyb2 strain. The selected recombinant strain possesses 6-fold increased DlDH activity as compared to the initial strain. The cellsdebris was used as a biorecognition element of a biosensor, since DlDH is strongly bound to mitochondrial membranes. The cellsdebris, prepared by mechanic disintegration of recombinant cells, was immobilized on a graphite working electrode in an electrochemically generated layer using an Os-complex modified cathodic electrodeposition polymer. Cytochrome c was used as additional native electron mediator to improve electron transfer from reduced DlDH to the working electrode. The constructed d-lactate-selective biosensors are characterized by a high sensitivity (46.3-61.6 A M-1 m-2), high selectivity and sufficient storage stability. © 2014 Elsevier B.V.
    view abstractdoi: 10.1016/j.talanta.2014.02.041
  • 2014 • 267 Artificial oxygen carriers based on perfluorodecalin-filled poly(n-butyl-cyanoacrylate) nanocapsules
    Stephan, C. and Schlawne, C. and Grass, S. and Waack, I.N. and Ferenz, K.B. and Bachmann, M. and Barnert, S. and Schubert, R. and Bastmeyer, M. and De Groot, H. and Mayer, C.
    Journal of Microencapsulation 31 284-292 (2014)
    Poly(n-butyl-cyanoacrylate)-nanocapsules filled by perfluorodecalin (PFD) are proposed as potential oxygen carriers for blood substitute. The capsule dispersion is prepared via interfacial polymerisation from a PFD emulsion in water which in turn is generated by spontaneous phase separation. The resulting dispersion is capable of carrying approximately 10% of its own volume of gaseous oxygen, which is approximately half of the capacity of human blood. The volumes of the organic solvents and water are varied within a wide range, connected to a change of the capsule radius between 200 and 400-nm. The principal suitability of the capsule dispersion for intravenous application is proven in first physiological experiments. A total amount of 10-ml/kg body weight has been infused into rats, with the dispersion supernatant and a normal saline solution as controls. After the infusion of nanocapsules, the blood pressure as well as the heart rate remains constant on a normal level. © 2014 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted.
    view abstractdoi: 10.3109/02652048.2013.843600
  • 2014 • 266 Gold nanoparticles interfere with sperm functionality by membrane adsorption without penetration
    Taylor, U. and Barchanski, A. and Petersen, S. and Kues, W.A. and Baulain, U. and Gamrad, L. and Sajti, L. and Barcikowski, S. and Rath, D.
    Nanotoxicology 8 118-127 (2014)
    To examine gold nanoparticle reprotoxicity, bovine spermatozoa were challenged with ligand-free or oligonucleotide-conjugated gold nanoparticles synthesized purely without any surfactants by laser ablation. Sperm motility declined at nanoparticle mass dose of 10 μg/ml (corresponding to ∼14 000 nanoparticles per sperm cell) regardless of surface modification. Sperm morphology and viability remained unimpaired at all concentrations. Transmission electron microscopy showed an modification dependant attachment of nanoparticles to the cell membrane of spermatozoa, but provided no evidence for nanoparticle entrance into sperm cells. A molecular examination revealed a reduction of free thiol residues on the cell membrane after nanoparticle exposure, which could explain the decrease in sperm motility. Sperm fertilising ability decreased after exposure to 10 μg/ml of ligand-free nanoparticles indicating that agglomerated ligand-free nanoparticles interfere with membrane properties necessary for fertilisation. In conclusion, nanoparticles may impair key sperm functions solely by interacting with the sperm surface membrane. © 2014 Informa UK Ltd. All rights reserved.
    view abstractdoi: 10.3109/17435390.2013.859321
  • 2014 • 265 Targeting and activation of antigen-specific B-cells by calcium phosphate nanoparticles loaded with protein antigen
    Temchura, V.V. and Kozlova, D. and Sokolova, V. and Überla, K. and Epple, M.
    Biomaterials 35 6098-6105 (2014)
    Cross-linking of the B-cell receptors of an antigen-specific B-cell is the initial signal for B-cell activation, proliferation, and differentiation into antibody secreting plasma cells. Since multivalent particulate structures are efficient activators of antigen-specific B-cells, we developed biodegradable calcium phosphate nanoparticles displaying protein antigens on their surface and explored the efficacy of the B-cell activation after exposure to these nanoparticles. The calcium phosphate nanoparticles were functionalized with the model antigen Hen Egg Lysozyme (HEL) to take advantage of a HEL-specific B-cell receptor transgenic mouse model. The nanoparticles were characterized by scanning electron microscopy and dynamic light scattering. The functionalized calcium phosphate nanoparticles were preferentially bound and internalized by HEL-specific B-cells. Co-cultivation of HEL-specific B-cells with the functionalized nanoparticles also increased surface expression of B-cell activation markers. Functionalized nanoparticles were able to effectively cross-link B-cell receptors at the surface of antigen-matched B-cells and were 100-fold more efficient in the activation of B-cells than soluble HEL. Thus, calcium phosphate nanoparticles coated with protein antigens are promising vaccine candidates for induction humoral immunity. © 2014 Elsevier Ltd.
    view abstractdoi: 10.1016/j.biomaterials.2014.04.010
  • 2014 • 264 Rapid identification of areas of interest in thin film materials libraries by combining electrical, optical, X-ray diffraction, and mechanical high-throughput measurements: A case study for the system ni-al
    Thienhaus, S. and Naujoks, D. and Pfetzing-Micklich, J. and König, D. and Ludwig, Al.
    ACS Combinatorial Science 16 686-694 (2014)
    The efficient identification of compositional areas of interest in thin film materials systems fabricated by combinatorial deposition methods is essential in combinatorial materials science. We use a combination of compositional screening by EDX together with high-throughput measurements of electrical and optical properties of thin film libraries to determine efficiently the areas of interest in a materials system. Areas of interest are compositions which show distinctive properties. The crystallinity of the thus determined areas is identified by X-ray diffraction. Additionally, by using automated nanoindentation across the materials library, mechanical data of the thin films can be obtained which complements the identification of areas of interest. The feasibility of this approach is demonstrated by using a Ni-Al thin film library as a reference system. The obtained results promise that this approach can be used for the case of ternary and higher order systems. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/co5000757
  • 2014 • 263 Conditioning of self-assembled monolayers at two static immersion test sites along the east coast of Florida and its effect on early fouling development
    Thome, I. and Bauer, S. and Vater, S. and Zargiel, K. and Finlay, J.A. and Arpa-Sancet, M.P. and Alles, M. and Callow, J.A. and Callow, M.E. and Swain, G.W. and Grunze, M. and Rosenhahn, A.
    Biofouling 30 1011-1021 (2014)
    Among the first events after immersion of surfaces in the ocean is surface ‘conditioning’. Here, the accumulation and composition of the conditioning films formed after immersion in the ocean are analyzed. In order to account for different surface chemistries, five self-assembled monolayers that differ in resistance to microfouling and wettability were used. Water samples from two static immersion test sites along the east coast of Florida were collected at two different times of the year and used for experiments. Spectral ellipsometry revealed that conditioning films were formed within the first 24 h and contact angle goniometry showed that these films changed the wettability and rendered hydrophobic surfaces more hydrophilic and vice versa. Infrared reflection adsorption spectroscopy showed that the composition of the conditioning film depended on both the wettability and immersion site. Laboratory and field assays showed that the presence of a conditioning film did not markedly influence settlement of microorganisms. © 2014, © 2014 Taylor & Francis.
    view abstractdoi: 10.1080/08927014.2014.957195
  • 2014 • 262 Catch me if you can: Challenges and applications of cross-linking approaches
    Tinnefeld, V. and Sickmann, A. and Ahrends, R.
    European Journal of Mass Spectrometry 20 99-116 (2014)
    Biomolecular complexes are the groundwork of life and the basis for cell signaling, energy transfer, motion, stability and cellular metabolism. Understanding the underlying complex interactions on the molecular level is an essential step to obtain a comprehensive insight into cellular and systems biology. For the investigation of molecular interactions, various methods, including Förster resonance energy transfer, nuclear magnetic resonance spectroscopy, X-ray crystallography and yeast two-hybrid screening, can be utilized. Nevertheless, the most reliable approach for structural proteomics and the identification of novel protein-binding partners is chemical cross-linking. The rationale is that upon forming a covalent bond between a protein and its interaction partner (protein, lipid, RNA/DNA, carbohydrate) the native complex state is "frozen" and accessible for detailed mass spectrometric analysis. In this review we provide a synopsis on crosslinker design, chemistry, pitfalls, limitations and novel applications in the field, and feature an overview of current software applications. © 2014 IM Publications LLP.
    view abstractdoi: 10.1255/ejms.1259
  • 2014 • 261 Impact of the configuration of a chiral, activating carrier on the enantioselectivity of entrapped lipase from Candida rugosa in cyclohexane
    Tobis, J. and Tiller, J.C.
    Biotechnology Letters 36 1661-1667 (2014)
    Lipase from Candida rugosa was loaded into an amphiphilic polymer co-network (APCN) composed of the chiral poly[(R)-N-(1-hydroxybutan-2-yl) acrylamide] [P-(R)-HBA] and P-(S)-HBA, respectively, linked by poly(dimethylsiloxane). The nanophase-separated amphiphilic morphology affords a 38,000-fold activation of the enzyme in the esterification of 1-phenylethanol with vinyl acetate. Further, the enantioselectivity of the entrapped lipase was influenced by the configuration of the chiral, hydrophilic polymer matrix. While the APCN with the (S)-configuration of the APCN affords 5.4 faster conversion of the (R)-phenylethanol compared to the respective (S)-enantiomer, the (R)-APCN allows an only a 2.8 faster conversion of the (R)-enantiomer of the alcohol. Permeation-experiments reveal that the enantioselectivity of the reaction is at least partially caused by specific interactions between the substrates and the APCN. © 2014 Springer Science+Business Media Dordrecht.
    view abstractdoi: 10.1007/s10529-014-1519-0
  • 2014 • 260 Nanoparticle impacts reveal magnetic field induced agglomeration and reduced dissolution rates
    Tschulik, K. and Compton, R.G.
    Physical Chemistry Chemical Physics 16 13909-13913 (2014)
    Superparamagnetic nanoparticles (NPs) are used in a variety of magnetic field-assisted chemical and medical applications, yet little of their fate during magnetic field interrogation is known. Here, fundamental and new insights in this are gained by cathodic particle coulometry. This methodology is used to study individual Fe3O4 NPs in the presence and absence of a magnetic field. It is first noticed that no major NP agglomeration occurs in the absence of a magnetic field even in a suspension of high ionic strength. In contrast, a significant magnetic field-induced agglomeration of NPs is observed in a magnetic field. A second new finding is that the dissolution of Fe 3O4 NPs is strongly inhibited in a magnetic field. This is explained as a result of the magnetic field gradient force trapping the released Fe2+ ions near the surface of a magnetized Fe 3O4 NP and thus hindering the mass-transport controlled NP dissolution. Consequently, fundamental magnetic field effects are measured and quantified on both the single NP scale and in suspension and two novel effects are discovered. This journal is © the Partner Organisations 2014.
    view abstractdoi: 10.1039/c4cp01618a
  • 2014 • 259 Electrical potential-assisted DNA hybridization. How to mitigate electrostatics for surface DNA hybridization
    Tymoczko, J. and Schuhmann, W. and Gebala, M.
    ACS Applied Materials and Interfaces 6 21851-21858 (2014)
    Surface-confined DNA hybridization reactions are sensitive to the number and identity of DNA capture probes and experimental conditions such as the nature and the ionic strength of the electrolyte solution. When the surface probe density is high or the concentration of bulk ions is much lower than the concentration of ions within the DNA layer, hybridization is significantly slowed down or does not proceed at all. However, high-density DNA monolayers are attractive for designing high-sensitivity DNA sensors. Thus, circumventing sluggish DNA hybridization on such interfaces allows a high surface concentration of target DNA and improved signal/noise ratio. We present potential-assisted hybridization as a strategy in which an external voltage is applied to the ssDNA-modified interface during the hybridization process. Results show that a significant enhancement of hybridization can be achieved using this approach. © 2014 American Chemical Society.
    view abstractdoi: 10.1021/am5027902
  • 2014 • 258 Correlating structure and ligand affinity in drug discovery: A cautionary tale involving second shell residues
    Tziridis, A. and Rauh, D. and Neumann, P. and Kolenko, P. and Menzel, A. and Bräuer, U. and Ursel, C. and Steinmetzer, P. and Stürzebecher, J. and Schweinitz, A. and Steinmetzer, T. and Stubbs, M.T.
    Biological Chemistry 395 891-903 (2014)
    A high-resolution crystallographic structure determination of a protein-ligand complex is generally accepted as the 'gold standard' for structure-based drug design, yet the relationship between structure and affinity is neither obvious nor straightforward. Here we analyze the interactions of a series of serine proteinase inhibitors with trypsin variants onto which the ligand-binding site of factor Xa has been grafted. Despite conservative mutations of only two residues not immediately in contact with ligands (second shell residues), significant differences in the affinity profiles of the variants are observed. Structural analyses demonstrate that these are due to multiple effects, including differences in the structure of the binding site, differences in target flexibility and differences in inhibitor binding modes. The data presented here highlight the myriad competing microscopic processes that contribute to protein-ligand interactions and emphasize the difficulties in predicting affinity from structure.
    view abstractdoi: 10.1515/hsz-2014-0158
  • 2014 • 257 Single core-shell nanoparticle probes for non-invasive magnetic force microscopy
    Uhlig, T. and Wiedwald, U. and Seidenstücker, A. and Ziemann, P. and Eng, L.M.
    Nanotechnology 25 (2014)
    We present an easy, fast and reliable method for the preparation of magnetic force microscopy (MFM) probes based on single Co nanoparticles (NPs). Due to their dipolar character, these magnetic probes open up a new approach for quantitative and non-invasive MFM measurements on the nanometer length scale. To guarantee long-term stability of these tips under ambient conditions, an ultrathin protecting Au shell was grown around the Co NPs through photochemical deposition. Single magnetic particles were firmly attached to standard silicon AFM tips using bifunctional self-assembling molecules. Such probes were tested on longitudinal magnetic recording media and compared to the results as recorded with conventional thin-film MFM tips. Easy data interpretation of the magnetic nanoparticle probes in a point dipole model is shown. Our nanoparticle tips provide excellent endurance for MFM recording, enable non-invasive probing while maintaining a high sensitivity, resolution, and reproducibility. © 2014 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0957-4484/25/25/255501
  • 2014 • 256 Apoptotic, inflammatory, and fibrogenic effects of two different types of multi-walled carbon nanotubes in mouse lung
    Van Berlo, D. and Wilhelmi, V. and Boots, A.W. and Hullmann, M. and Kuhlbusch, T.A.J. and Bast, A. and Schins, R.P.F. and Albrecht, C.
    Archives of Toxicology 88 1725-1737 (2014)
    There is increasing concern about the toxicity of inhaled multi-walled carbon nanotubes (MWCNTs). Pulmonary macrophages represent the primary cell type involved in the clearance of inhaled particulate materials, and induction of apoptosis in these cells has been considered to contribute to the development of lung fibrosis. We have investigated the apoptotic, inflammogenic, and fibrogenic potential of two types of MWCNTs, characterised by a contrasting average tube length and entanglement/agglomeration. Both nanotube types triggered H2O2 formation by RAW 264.7 macrophages, but in vitro toxicity was exclusively seen with the longer MWCNT. Both types of nanotubes caused granuloma in the mouse lungs. However, the long MWCNT induced a more pronounced pro-fibrotic (mRNA expression of matrix metalloproteinase-8 and tissue inhibitor of metalloproteinase-1) and inflammatory (serum level of monocyte chemotactic protein-1) response. Masson trichrome staining also revealed epithelial cell hyperplasia for this type of MWCNT. Enhanced apoptosis was detected by cleaved caspase 3 immunohistochemistry in lungs of mice treated with the long and rigid MWCNT and, to a lesser extent, with the shorter, highly agglomerated MWCNT. However, staining was merely localised to granulomatous foci, and neither of the MWCNTs induced apoptosis in vitro, evaluated by caspase 3/7 activity in RAW 264.7 cells. In addition, our study reveals that the inflammatory and pro-fibrotic effects of MWCNTs in the mouse lung can vary considerably depending on their composition. The in vitro analysis of macrophage apoptosis appears to be a poor predictor of their pulmonary hazard. © 2014 Springer-Verlag.
    view abstractdoi: 10.1007/s00204-014-1220-z
  • 2014 • 255 A fluorescent light-up probe as an inhibitor of intracellular beta-tryptase
    Wang, Q. and Shi, X. Y. and Zhu, X. X. and Ehlers, M. and Wu, J. C. and Schmuck, C.
    Chemical Communications 50 6120--6122 (2014)
    A pyrene-functionalized peptidic inhibitor 1 binds to and inhibits beta-tryptase in a non-competitive and reversible manner even in cells. Upon protein binding a fluorescence increase of the two pyrene fluorophores is observed which allows using 1 as a fluorescent light-up probe for this enzyme.
    view abstractdoi: 10.1039/c4cc02208d
  • 2014 • 254 Platinum-cobalt bimetallic nanoparticles in hollow carbon nanospheres for hydrogenolysis of 5-hydroxymethylfurfural
    Wang, G.-H. and Hilgert, J. and Richter, F.H. and Wang, F. and Bongard, H.-J. and Spliethoff, B. and Weidenthaler, C. and Schüth, F.
    Nature Materials 13 293-300 (2014)
    The synthesis of 2,5-dimethylfuran (DMF) from 5-hydroxymethylfurfural (HMF) is a highly attractive route to a renewable fuel. However, achieving high yields in this reaction is a substantial challenge. Here it is described how PtCo bimetallic nanoparticles with diameters of 3.6 ± 0.7 nm can solve this problem. Over PtCo catalysts the conversion of HMF was 100% within 10 min and the yield to DMF reached 98% after 2 h, which substantially exceeds the best results reported in the literature. Moreover, the synthetic method can be generalized to other bimetallic nanoparticles encapsulated in hollow carbon spheres. © 2014 Macmillan Publishers Limited.
    view abstractdoi: 10.1038/nmat3872
  • 2014 • 253 X-ray reflectivity measurements of liquid/solid interfaces under high hydrostatic pressure conditions
    Wirkert, F.J. and Paulus, M. and Nase, J. and Möller, J. and Kujawski, S. and Sternemann, C. and Tolan, M.
    Journal of Synchrotron Radiation 21 76-81 (2014)
    A high-pressure cell for in situ X-ray reflectivity measurements of liquid/solid interfaces at hydrostatic pressures up to 500 MPa (5 kbar), a pressure regime that is particularly important for the study of protein unfolding, is presented. The original set-up of this hydrostatic high-pressure cell is discussed and its unique properties are demonstrated by the investigation of pressure-induced adsorption of the protein lysozyme onto hydrophobic silicon wafers. The presented results emphasize the enormous potential of X-ray reflectivity studies under high hydrostatic pressure conditions for the in situ investigation of adsorption phenomena in biological systems.© 2014 International Union of Crystallography.
    view abstractdoi: 10.1107/S1600577513021516
  • 2014 • 252 Feedback mechanism for microtubule length regulation by stathmin gradients
    Zeitz, M. and Kierfeld, J.
    Biophysical Journal 107 2860-2871 (2014)
    We formulate and analyze a theoretical model for the regulation of microtubule (MT) polymerization dynamics by the signaling proteins Rac1 and stathmin. In cells, the MT growth rate is inhibited by cytosolic stathmin, which, in turn, is inactivated by Rac1. Growing MTs activate Rac1 at the cell edge, which closes a positive feedback loop. We investigate both tubulin sequestering and catastrophe promotion as mechanisms for MT growth inhibition by stathmin. For a homogeneous stathmin concentration in the absence of Rac1, we find a switchlike regulation of the MT mean length by stathmin. For constitutively active Rac1 at the cell edge, stathmin is deactivated locally, which establishes a spatial gradient of active stathmin. In this gradient, we find a stationary bimodal MT-length distribution for both mechanisms of MT growth inhibition by stathmin. One subpopulation of the bimodal length distribution can be identified with fast-growing and long pioneering MTs in the region near the cell edge, which have been observed experimentally. The feedback loop is closed through Rac1 activation by MTs. For tubulin sequestering by stathmin, this establishes a bistable switch with two stable states: one stable state corresponds to upregulated MT mean length and bimodal MT length distributions, i.e., pioneering MTs; the other stable state corresponds to an interrupted feedback with short MTs. Stochastic effects as well as external perturbations can trigger switching events. For catastrophe-promoting stathmin, we do not find bistability. © 2014 Biophysical Society.
    view abstractdoi: 10.1016/j.bpj.2014.10.056
  • 2014 • 251 Gold and silver nanoparticle monomers are non-SERS-active: A negative experimental study with silica-encapsulated Raman-reporter-coated metal colloids
    Zhang, Y. and Walkenfort, B. and Yoon, J.H. and Schlücker, S. and Xie, W.
    Physical Chemistry Chemical Physics 17 21120-21126 (2014)
    Noble metal nanoparticles (NPs) are the most commonly employed plasmonic substrates in surface-enhanced Raman scattering (SERS) experiments. Computer simulations show that monomers of Ag and Au nanocrystals ("spherical" NPs) do not exhibit a notable plasmonic enhancement, i.e., they are essentially non-SERS-active. However, in experiments, SERS enhanced by spherical NP colloids has been frequently reported. This implies that the monomers do not have strong SERS activity, but detectable enhancement should more or less be there. Because of the gap between theory and practice, it is important to demonstrate experimentally how SERS-active the metal colloid actually is and, in case a SERS signal is observed, where it originates from. In particular the aggregation of the colloid, induced by high centrifugal forces in washing steps or due to a harsh ionic environment of the suspension medium, should be controlled since it is the very high SERS activity of NP clusters which dominates the overall SERS signal of the colloid. We report here the experimental evaluation of the SERS activity of 80 nm Au and Ag NP monomers. Instead of showing fancy nanostructures and super SERS enhancement, we present the method on how to obtain negative experimental data. In this approach, no SERS signal was obtained from the colloid with a Raman reporter on the metal surface when the NPs were encapsulated carefully within a thick silica shell. Without silica encapsulation, if a very low centrifugation speed is used for the washing steps, only a negligible SERS signal can be detected even at very high NP concentrations. In contrast, strong SERS signals can be detected when the NPs are suspended in acidic solutions. These results indicate that Au and Ag NP monomers essentially exhibit no SERS activity of practical relevance. © the Owner Societies 2015.
    view abstractdoi: 10.1039/c4cp05073h
  • 2013 • 250 Detection of nitric oxide and nitroxyl with benzoresorufin-based fluorescent sensors
    Apfel, U.-P. and Buccella, D. and Wilson, J.J. and Lippard, S.J.
    Inorganic Chemistry 52 3285-3294 (2013)
    A new family of benzoresorufin-based copper complexes for fluorescence detection of NO and HNO is reported. The copper complexes, CuBRNO1-3, elicit 1.5-4.8-fold emission enhancement in response to NO and HNO. The three sensors differ in the nature of the metal-binding site. The photophysical properties of these sensors are investigated with assistance from density functional theory calculations. The fluorescence turn-on observed upon reaction with HNO is an unexpected result that is discussed in detail. The utility of the new sensors for detecting HNO and NO in HeLa cells and RAW 264.7 macrophages is demonstrated. © 2013 American Chemical Society.
    view abstractdoi: 10.1021/ic302793w
  • 2013 • 249 Advanced nanoparticle generation and excitation by lasers in liquids
    Barcikowski, S. and Compagnini, G.
    Physical Chemistry Chemical Physics 15 3022-3026 (2013)
    Today, nanoparticles are widely implemented as functional elements onto surfaces, into volumes and as nano-hybrids, resulting for example in bioactive composites and biomolecule conjugates. However, only limited varieties of materials compatible for integration into advanced functional materials are available: nanoparticles synthesized using conventional gas phase processes are often agglomerated into micro powders that are hard to re-disperse into functional matrices. Chemical synthesis methods often lead to impurities of the nanoparticle colloids caused by additives and precursor reaction products. In the last decade, laser ablation and nanoparticle generation in liquids has proven to be a unique and efficient technique to generate, excite, fragment, and conjugate a large variety of nanostructures in a scalable and clean manner. This editorial briefly highlights selected recent advancements and critical aspects in the field of pulsed laser-based nanoparticle generation and manipulation, including exemplary strategies to harvest the unique properties of the laser-generated nanomaterials in the field of biomedicine and catalysis. The presented critical aspects address future assignments such as size control and scale-up. This journal is © 2013 the Owner Societies.
    view abstractdoi: 10.1039/c2cp90132c
  • 2013 • 248 Debye relaxation and 250 K anomaly in glass forming monohydroxy alcohols
    Bauer, S. and Burlafinger, K. and Gainaru, C. and Lunkenheimer, P. and Hiller, W. and Loidl, A. and Böhmer, R.
    Journal of Chemical Physics 138 (2013)
    A previous dielectric, near-infrared (NIR), and nuclear magnetic resonance study on the hydrogen-bonded liquid 2-ethyl-1-hexanol C. Gainaru, Phys. Rev. Lett. 107, 118304 (2011)10.1103/PhysRevLett.107.118304 revealed anomalous behavior in various static quantities near 250 K. To check whether corresponding observations can be made for other monohydroxy alcohols as well, these experimental methods were applied to such substances with 5, 6, 7, 8, and 10 carbon atoms in their molecular backbone. All studied liquids exhibit a change of behavior near 250 K, which is tentatively ascribed to effects of hydrogen bond cooperativity. By analyzing the NIR band intensities, a linear cluster size is derived that agrees with estimates from dielectric spectroscopy. All studied alcohols, except 4-methyl-3-heptanol, display a dominant Debye-like peak. Furthermore, neat 2-ethyl-1-butanol exhibits a well resolved structural relaxation in its dielectric loss spectrum, which so far has only been observed for diluted monohydroxy alcohols. © 2013 American Institute of Physics.
    view abstractdoi: 10.1063/1.4793469
  • 2013 • 247 Adhesion of marine fouling organisms on hydrophilic and amphiphilic polysaccharides
    Bauer, S. and Arpa-Sancet, M.P. and Finlay, J.A. and Callow, M.E. and Callow, J.A. and Rosenhahn, A.
    Langmuir 29 4039-4047 (2013)
    Polysaccharides are a promising material for nonfouling surfaces because their chemical composition makes them highly hydrophilic and able to form water-storing hydrogels. Here we investigated the nonfouling properties of hyaluronic acid (HA) and chondroitin sulfate (CS) against marine fouling organisms. Additionally, the free carboxyl groups of HA and CS were postmodified with the hydrophobic trifluoroethylamine (TFEA) to block free carboxyl groups and render the surfaces amphiphilic. All coatings were tested with respect to their protein resistance and against settlement and adhesion of different marine fouling species. Both the settlement and adhesion strength of a marine bacterium (Cobetia marina), zoospores of the seaweed Ulva linza, and cells of a diatom (Navicula incerta) were reduced compared to glass control surfaces. In most cases, TFEA capping increased or maintained the performance of the HA coatings, whereas for the very well performing CS coatings the antifouling performance was reduced after capping. © 2013 American Chemical Society.
    view abstractdoi: 10.1021/la3038022
  • 2013 • 246 Molecular tweezers modulate 14-3-3 protein-protein interactions
    Bier, D. and Rose, R. and Bravo-Rodriguez, K. and Bartel, M. and Ramirez-Anguita, J.M. and Dutt, S. and Wilch, C. and Klärner, F.-G. and Sanchez-Garcia, E. and Schrader, T. and Ottmann, C.
    Nature Chemistry 5 234-239 (2013)
    Supramolecular chemistry has recently emerged as a promising way to modulate protein functions, but devising molecules that will interact with a protein in the desired manner is difficult as many competing interactions exist in a biological environment (with solvents, salts or different sites for the target biomolecule). We now show that lysine-specific molecular tweezers bind to a 14-3-3 adapter protein and modulate its interaction with partner proteins. The tweezers inhibit binding between the 14-3-3 protein and two partner proteins-a phosphorylated (C-Raf) protein and an unphosphorylated one (ExoS)-in a concentration-dependent manner. Protein crystallography shows that this effect arises from the binding of the tweezers to a single surface-exposed lysine (Lys214) of the 14-3-3 protein in the proximity of its central channel, which normally binds the partner proteins. A combination of structural analysis and computer simulations provides rules for the tweezers' binding preferences, thus allowing us to predict their influence on this type of protein-protein interactions. © 2013 Macmillan Publishers Limited. All rights reserved.
    view abstractdoi: 10.1038/nchem.1570
  • 2013 • 245 Towards a spectroscopic and theoretical identification of the isolated building blocks of the benzene-acetylene cocrystal
    Böning, M. and Stuhlmann, B. and Engler, G. and Busker, M. and Häber, T. and Tekin, A. and Jansen, G. and Kleinermanns, K.
    ChemPhysChem 14 837-846 (2013)
    Isomer- and mass-selective UV and IR-UV double resonance spectra of the BA3, B2A, and B2A2 clusters of benzene (B) and acetylene (A) are presented. Cluster structures are assigned by comparison with the UV and IR spectra of benzene, the benzene dimer, as well as the BA, BA2, and B2A clusters. The intermolecular vibrations of BA are identified by dispersed fluorescence spectroscopy. Assignment of the cluster structures is supported by quantum chemical calculations of IR spectra with spin-component scaled second-order Møller-Plesset (SCS-MP2) theory. Initial propositions for various structures of the BA3 and B2A2 aggregates are generated with model potentials based on density functional theory combined with the symmetry-adapted perturbation theory (DFT-SAPT) approach. Shape and relative cluster stabilities are then confirmed with SCS-MP2. T-shaped geometries are the dominant structural motifs. Higher-energy isomers are also observed. The detected cluster structures are correlated with possible cluster formation pathways and their role as crystallization seeds is discussed. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cphc.201200701
  • 2013 • 244 High-throughput compositional and structural evaluation of a Li a(NixMnyCoz)Or thin film battery materials library
    Borhani-Haghighi, S. and Kieschnick, M. and Motemani, Y. and Savan, A. and Rogalla, D. and Becker, H.-W. and Meijer, J. and Ludwig, Al.
    ACS Combinatorial Science 15 401-409 (2013)
    A Lia(NixMnyCoz)Or cathode materials library was fabricated by combinatorial magnetron sputtering. The compositional analysis of the library was performed by a new high-throughput approach for Li-content measurement in thin films, which combines automated energy-dispersive X-ray spectroscopy, Deuteron-induced gamma emission, and Rutherford backscattering measurements. Furthermore, combining this approach with thickness measurements allows the mapping of density values of samples from the materials library. By correlating the obtained compositional data with structural data from high-throughput X-ray diffraction measurements, those compositions which show a layered (R3Ì...m) structure and are therefore most interesting for Li-battery applications (for cathode (positive) electrodes) can be rapidly identified. This structure was identified as being most pronounced in the compositions Li0.6(Ni0.16Mn 0.35Co0.48)O2, Li0.7(Ni 0.10Mn0.37Co0.51)O2, Li 0.6(Ni0.23Mn0.33Co0.43)O 2, Li0.3(Ni0.65Mn0.08Co 0.26)O2, Li0.3(Ni0.63Mn 0.08Co0.29)O2, Li0.4(Ni 0.56Mn0.09Co0.34)O2, Li 0.5(Ni0.45Mn0.13Co0.42)O 2, and Li0.6(Ni0.34Mn0.14Co 0.52)O2. © 2013 American Chemical Society.
    view abstractdoi: 10.1021/co4000166
  • 2013 • 243 Comparison of analytic and numerical bond-order potentials for W and Mo
    Čák, M. and Hammerschmidt, T. and Drautz, R.
    Journal of Physics Condensed Matter 25 (2013)
    Bond-order potentials (BOPs) are derived from the tight-binding approximation and provide a linearly-scaling computation of the energy and forces for a system of interacting atoms. While the numerical BOPs involve the numerical integration of the response (Green's) function, the expressions for the energy and interatomic forces are analytical within the formalism of the analytic BOPs. In this paper we present a detailed comparison of numerical and analytic BOPs. We use established parametrizations for the bcc refractory metals W and Mo and test structural energy differences; tetragonal, trigonal, hexagonal and orthorhombic deformation paths; formation energies of point defects as well as phonon dispersion relations. We find that the numerical and analytic BOPs generally are in very good agreement for the calculation of energies. Different from the numerical BOPs, the forces in the analytic BOPs correspond exactly to the negative gradients of the energy. This makes it possible to use the analytic BOPs in dynamical simulations and leads to improved predictions of defect energies and phonons as compared to the numerical BOPs. © 2013 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0953-8984/25/26/265002
  • 2013 • 242 A robust nickel catalyst for cyanomethylation of aldehydes: Activation of acetonitrile under base-free conditions
    Chakraborty, S. and Patel, Y.J. and Krause, J.A. and Guan, H.
    Angewandte Chemie - International Edition 52 7523-7526 (2013)
    Nick of time: The nickel cyanomethyl complex 1 catalyzes the room temperature coupling of aldehydes with acetonitrile under base-free conditions. The catalytic system is long-lived and remarkably efficient with high turnover numbers (TONs) and turnover frequencies (TOFs) achieved. The mild reaction conditions allow a wide variety of aldehydes, including base-sensitive ones, to catalytically react with acetonitrile. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201302613
  • 2013 • 241 Pincer-ligated nickel hydridoborate complexes: The dormant species in catalytic reduction of carbon dioxide with boranes
    Chakraborty, S. and Zhang, J. and Patel, Y.J. and Krause, J.A. and Guan, H.
    Inorganic Chemistry 52 37-47 (2013)
    Nickel pincer complexes of the type [2,6-(R2PO) 2C6H3]NiH (R = tBu, 1a; R = iPr, 1b; R = cPe, 1c) react with BH3·THF to produce borohydride complexes [2,6-(R2PO)2C 6H3]Ni(η2-BH4) (2a-c), as confirmed by NMR and IR spectroscopy, X-ray crystallography, and elemental analysis. The reactions are irreversible at room temperature but reversible at 60 C. Compound 1a exchanges its hydrogen on the nickel with the borane hydrogen of 9-BBN or HBcat, but does not form any observable adduct. The less bulky hydride complexes 1b and 1c, however, yield nickel dihydridoborate complexes reversibly at room temperature when mixed with 9-BBN and HBcat. The dihydridoborate ligand in these complexes adopts an η2- coordination mode, as suggested by IR spectroscopy and X-ray crystallography. Under the catalytic influence of 1a-c, reduction of CO2 leads to the methoxide level when 9-BBN or HBcat is employed as the reducing agent. The best catalyst, 1a, involves bulky substituents on the phosphorus donor atoms. Catalytic reactions involving 1b and 1c are less efficient because of the formation of dihydridoborate complexes as the dormant species as well as partial decomposition of the catalysts by the boranes. © 2012 American Chemical Society.
    view abstractdoi: 10.1021/ic300587b
  • 2013 • 240 Silver as antibacterial agent: Ion, nanoparticle, and metal
    Chernousova, S. and Epple, M.
    Angewandte Chemie - International Edition 52 1636-1653 (2013)
    The antibacterial action of silver is utilized in numerous consumer products and medical devices. Metallic silver, silver salts, and also silver nanoparticles are used for this purpose. The state of research on the effect of silver on bacteria, cells, and higher organisms is summarized. It can be concluded that the therapeutic window for silver is narrower than often assumed. However, the risks for humans and the environment are probably limited. Silver shield: Silver is used in different forms as an antibacterial agent. Earlier, sparingly soluble silver salts were predominantly used, but today, silver nanoparticles (see picture for an SEM image of cubic silver nanoparticles) are gaining increasing importance. As silver is also toxic towards mammalian cells, there is the question of the therapeutic window in the cases of consumer products and medical devices. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201205923
  • 2013 • 239 Atom Probe Tomography Studies on the Cu(In,Ga)Se-2 Grain Boundaries
    Cojocaru-Miredin, O. and Schwarz, T. and Choi, P. P. and Herbig, M. and Wuerz, R. and Raabe, D.
    Jove-journal of Visualized Experiments UNSP e50376 (2013)
    Compared with the existent techniques, atom probe tomography is a unique technique able to chemically characterize the internal interfaces at the nanoscale and in three dimensions. Indeed, APT possesses high sensitivity (in the order of ppm) and high spatial resolution (sub nm). Considerable efforts were done here to prepare an APT tip which contains the desired grain boundary with a known structure. Indeed, sitespecific sample preparation using combined focused-ion-beam, electron backscatter diffraction, and transmission electron microscopy is presented in this work. This method allows selected grain boundaries with a known structure and location in Cu(In, Ga)Se-2 thin-films to be studied by atom probe tomography. Finally, we discuss the advantages and drawbacks of using the atom probe tomography technique to study the grain boundaries in Cu(In,Ga)Se-2 thin-film solar cells.
    view abstractdoi: 10.3791/50376
  • 2013 • 238 Molecular tweezers with varying anions: A comparative study
    Dutt, S. and Wilch, C. and Gersthagen, T. and Talbiersky, P. and Bravo-Rodriguez, K. and Hanni, M. and Sánchez-García, E. and Ochsenfeld, C. and Klärner, F.-G. and Schrader, T.
    Journal of Organic Chemistry 78 6721-6734 (2013)
    Selective binding of the phosphate-substituted molecular tweezer 1a to protein lysine residues was suggested to explain the inhibition of certain enzymes and the aberrant aggregation of amyloid petide Aβ42 or α-synuclein, which are assumed to be responsible for Alzheimer's and Parkinson's disease, respectively. In this work we systematically investigated the binding of four water-soluble tweezers 1a-d (substituted by phosphate, methanephosphonate, sulfate, or O-methylenecarboxylate groups) to amino acids and peptides containing lysine or arginine residues by using fluorescence spectroscopy, NMR spectroscopy, and isothermal titration calorimetry (ITC). The comparison of the experimental results with theoretical data obtained by a combination of QM/MM and ab initio1H NMR shift calculations provides clear evidence that the tweezers 1a-c bind the amino acid or peptide guest molecules by threading the lysine or arginine side chain through the tweezers' cavity, whereas in the case of 1d the guest molecule is preferentially positioned outside the tweezer's cavity. Attractive ionic, CH-π, and hydrophobic interactions are here the major binding forces. The combination of experiment and theory provides deep insight into the host-guest binding modes, a prerequisite to understanding the exciting influence of these tweezers on the aggregation of proteins and the activity of enzymes. © 2013 American Chemical Society.
    view abstractdoi: 10.1021/jo4009673
  • 2013 • 237 Response: platelet transcriptome and proteome--relation rather than correlation.
    Geiger, J. and Burkhart, J.M. and Gambaryan, S. and Walter, U. and Sickmann, A. and Zahedi, R.P.
    Blood 121 5257-5258 (2013)
    doi: 10.1182/blood-2013-04-493403
  • 2013 • 236 At-line measurement of lactose in dairy-processing plants
    Glithero, N. and Clark, C. and Gorton, L. and Schuhmann, W. and Pasco, N.
    Analytical and Bioanalytical Chemistry 405 3791-3799 (2013)
    Environmental and process control applications have needs for sensors that operate continuously or repeatedly, making them applicable to batch measurement and flowing product stream measurement. Additionally, for lactose monitoring in dairy-processing plants, the sensors must have sufficient flexibility to handle a wide range of substrate concentration and be resilient to withstand wide pH excursions brought about by frequent exposure to clean-in-place chemicals that happen without any warning. This paper describes the development and trialling of an at-line lactose biosensor that meets the needs of the dairy industry for loss monitoring of lactose in dairy-processing plants by the combination of a third-generation enzyme biosensor with a sequential injection analyser. Results, both from grab sample analysis and an at-line factory prototype, are shown from their operation when installed at a Fonterra dairy factory (New Zealand) during the 2011-2012 season. Previous sensor fabrication methods were converted to a single-step process, and the flow-through cell was adapted to bubble-free operation. The lactose concentration in wastewater-processing streams was successfully monitored by taking and analysing samples every 2-3 min, semi-continuously, for 3 months by an unskilled operator. The Fonterra site flushes approximately 100-300,000 L of wastewater per hour from its lactose plant. In the 2011-2012 season, the daily mean lactose content of this wastewater varied significantly, from 0.0 to 8.0 % w/v (0-233,712 μM) and equated to substantial total losses of lactose over a 6-month period. These lactose losses represent lost saleable or useable product. © 2012 Springer-Verlag Berlin Heidelberg.
    view abstractdoi: 10.1007/s00216-012-6598-y
  • 2013 • 235 Interfacial roughening in nonideal fluids: Dynamic scaling in the weak- and strong-damping regime
    Gross, M. and Varnik, F.
    Physical Review E - Statistical, Nonlinear, and Soft Matter Physics 87 (2013)
    Interfacial roughening denotes the nonequilibrium process by which an initially flat interface reaches its equilibrium state, characterized by the presence of thermally excited capillary waves. Roughening of fluid interfaces has been first analyzed by Flekkoy and Rothman, where the dynamic scaling exponents in the weakly damped case in two dimensions were found to agree with the Kardar-Parisi-Zhang universality class. We extend this work by taking into account also the strong-damping regime and perform extensive fluctuating hydrodynamics simulations in two dimensions using the Lattice Boltzmann method. We show that the dynamic scaling behavior is different in the weakly and strongly damped case. © 2013 American Physical Society.
    view abstractdoi: 10.1103/PhysRevE.87.022407
  • 2013 • 234 The biocompatibility of dense and porous Nickel-Titanium produced by selective laser melting
    Habijan, T. and Haberland, C. and Meier, H. and Frenzel, J. and Wittsiepe, J. and Wuwer, C. and Greulich, C. and Schildhauer, T.A. and Köller, M.
    Materials Science and Engineering C 33 419-426 (2013)
    Nickel-Titanium shape memory alloys (NiTi-SMA) are of biomedical interest due to their unusual range of pure elastic deformability and their elastic modulus, which is closer to that of bone than any other metallic or ceramic material. Newly developed porous NiTi, produced by Selective Laser Melting (SLM), is currently under investigation as a potential carrier material for human mesenchymal stem cells (hMSC). SLM enables the production of highly complex and tailor-made implants for patients on the basis of CT data. Such implants could be used for the reconstruction of the skull, face, or pelvis. hMSC are a promising cell type for regenerative medicine and tissue engineering due to their ability to support the regeneration of critical size bone defects. Loading porous SLM-NiTi implants with autologous hMSC may enhance bone growth and healing for critical bone defects. The purpose of this study was to assess whether porous SLM-NiTi is a suitable carrier for hMSC. Specimens of varying porosity and surface structure were fabricated via SLM. hMSC were cultured for 8 days on NiTi specimens, and cell viability was analyzed using two-color fluorescence staining. Viable cells were detected on all specimens after 8 days of cell culture. Cell morphology and surface topography were analyzed by scanning electron microscopy (SEM). Cell morphology and surface topology were dependent on the orientation of the specimens during SLM production. The Nickel ion release can be reduced significantly by aligned laser processing conditions. The presented results clearly attest that both dense SLM-NiTi and porous SLM-NiTi are suitable carriers for hMSC. Nevertheless, before carrying out in vivo studies, some work on optimization of the manufacturing process and post-processing is required. © 2012 Elsevier B.V.
    view abstractdoi: 10.1016/j.msec.2012.09.008
  • 2013 • 233 Counterion-mediated hierarchical self-assembly of an ABC miktoarm star terpolymer
    Hanisch, A. and Gröschel, A.H. and Förtsch, M. and Drechsler, M. and Jinnai, H. and Ruhland, T.M. and Schacher, F.H. and Müller, A.H.E.
    ACS Nano 7 4030-4041 (2013)
    Directed self-assembly processes of polymeric systems represent a powerful approach for the generation of structural hierarchy in analogy to biological systems. Herein, we utilize triiodide as a strongly polarizable counterion to induce hierarchical self-assembly of an ABC miktoarm star terpolymer comprising a polybutadiene (PB), a poly(tert-butyl methacrylate) (PtBMA), and a poly(N-methyl-2-vinylpyridinium) (P2VPq) segment. Hereby, the miktoarm architecture in conjunction with an increasing ratio of triiodide versus iodide counterions allows for a stepwise assembly of spherical micelles as initial building blocks into cylindrical structures and superstructures thereof. Finally, micrometer-sized multicompartment particles with a periodic lamellar fine structure are observed, for which we introduce the term "woodlouse". The counterion-mediated decrease in hydrophilicity of the corona-forming P2VPq block is the underlying trigger to induce this hierarchical structure formation. All individual steps and the corresponding intermediates toward these well-defined superstructures were intensively studied by scattering and electron microscopic techniques, including transmission electron microtomography. © 2013 American Chemical Society.
    view abstractdoi: 10.1021/nn400031u
  • 2013 • 232 Lipid-based intravesical drug delivery systems with controlled release of trospium chloride for the urinary bladder
    Haupt, M. and Thommes, M. and Heidenreich, A. and Breitkreutz, J.
    Journal of Controlled Release 170 161-166 (2013)
    The overactive bladder (OAB) is a common disease with an overactivity of the detrusor muscle in the bladder wall. Besides peroral administration of anticholinergic drugs and bladder irrigations, there is a need for a sustained release formulation in the urinary bladder. In order to realise a local long-term treatment of the overactive urinary bladder, lipidic drug delivery systems were prepared. Requirements for an intravesical application are a long-term controlled release of trospium chloride, a high drug loading and small sized drug carriers to permit an insertion through the urethra into the urinary bladder. The drug delivery systems were manufactured by using compression (mini-tablets), solid lipid extrusion (extrudates) and a melting and casting technique (mini-moulds) with different amounts of trospium chloride and glyceryl tristearate as matrix former. Drug release depended on the drug loading and the preparation method. Mini-tablets and lipidic extrudates showed a drug release over five days, whereas that from mini-moulds was negligibly small. The appearance of polymorphic transformations during processing and storage was investigated by using differential scanning calorimetry and X-ray diffraction. In contrast to mini-tablets and mini-moulds, lipidic extrudates showed no polymorphic transformations. In summary, lipids are suitable matrix formers for a highly water-soluble drug, like trospium chloride. Despite a drug loading of up to 30%, it was feasible to achieve a drug release ranging from several days up to weeks. In addition, small dosage forms with a size of only a few millimetres were realised. Therefore, an insertion and excretion through the urethra is possible and the requirements for an intravesical application are fulfilled. © 2013 Elsevier B.V. All rights reserved.
    view abstractdoi: 10.1016/j.jconrel.2013.05.018
  • 2013 • 231 Stress-induced stabilization of crystals in shape memory natural rubber
    Heuwers, B. and Quitmann, D. and Hoeher, R. and Reinders, F.M. and Tiemeyer, S. and Sternemann, C. and Tolan, M. and Katzenberg, F. and Tiller, J.C.
    Macromolecular Rapid Communications 34 180-184 (2013)
    In contrast to all known shape memory polymers, the melting temperature of crystals in shape memory natural rubber (SMNR) can be greatly manipulated by the application of external mechanical stress. As shown previously, stress perpendicular to the prior programming direction decreases the melting temperature by up to 40 K. In this study, we investigated the influence of mechanical stress parallel to prior stretching direction during programming on the stability of the elongation-stabilizing crystals. It was found that parallel stress stabilizes the crystals, which is indicated by linear increase of the trigger temperature by up to 17 K. The crystal melting temperature can be increased up to 126.5 °C under constrained conditions as shown by X-ray diffraction measurements. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/marc.201200594
  • 2013 • 230 Nanoscale thermomechanics of wear-resilient polymeric bilayer systems
    Kaule, T. and Zhang, Y. and Emmerling, S. and Pihan, S. and Foerch, R. and Gutmann, J. and Butt, H.-J. and Berger, R. and Duerig, U. and Knoll, A.W.
    ACS Nano 7 748-759 (2013)
    We explore the effect of an ultrathin elastic coating to optimize the mechanical stability of an underlying polymer film for nanoscale applications. The coating consists of a several nanometer thin plasma-polymerized norbornene layer. Scanning probes are used to characterize the system in terms of shear-force-induced wear and thermally assisted indentation. The layer transforms a weakly performing polystyrene film into a highly wear-resistive system, ideal for high-density and low-power data storage applications. The result can be understood from the indentation characteristics with a hot and sharp indenter tip. The latter gives rise to a deformation mode in the fully plastic regime, enabling a simple interpretation of the results. The softening transition and the yield stress of the system on a microsecond time scale and a nanometer size scale were obtained. We show that the plastic deformation is governed by yielding in the polystyrene sublayer, which renders the overall system soft for plastic deformation. The ultrathin protection layer contributes as an elastic skin, which shields part of the temperature and pressure and enables the high wear resistance against lateral forces. Moreover, the method of probing polymers at microsecond and nanometer size scales opens up new opportunities for studying polymer physics in a largely unexplored regime. Thus, we find softening temperatures of more than 100 °C above the polystyrene glass transition, which implies that for the short interaction time scales the glassy state of the polymer is preserved up to this temperature. © 2012 American Chemical Society.
    view abstractdoi: 10.1021/nn305047m
  • 2013 • 229 Aromatic interactions by molecular tweezers and clips in chemical and biological systems
    Klärner, F.-G. and Schrader, T.
    Accounts of Chemical Research 46 967-978 (2013)
    Noncovalent interactions involving aromatic rings, such as π-stacking and CH-π, occur throughout a range of fundamental processes including self-assembly and (bio)catalysis. Molecular clips and tweezers possess a central parallel or torus-shaped cavity with a surrounding belt of convergent aromatic rings; hence these structures exploit multiple aromatic interactions in a positively cooperative manner. Both clips and tweezers demonstrate selective binding of cationic or neutral guests that bear acceptor groups. The electrostatic surface potentials (ESP) explain this unexpected behavior: calculated ESPs were highly negative inside the tweezer or clip cavity, providing complementary profiles to the positive ESP plots of their preferred guest molecules. This Account presents more complex systems that use aromatic clips and tweezers to alter the reactivities of included guest species, to distinguish between guest enantiomers, and to interfere with biological processes such as enzymatic activity and protein aggregation.Napthalene tweezers show potential applications in organocatalysis. When pyridinium moieties are bound within the spacious cavity of naphthyl-spaced tweezers, the resulting complex significantly influences the first step of single-electron reductions of (bi)pyridinium salts. In addition, the environment within the tweezer cavity strongly accelerates the Menshutkin reaction (the alkylation of pyridine derivatives).Introduction of phosphonate, phosphate, or sulfate anions into the central aromatic bridge renders clips and tweezers water-soluble. Larger systems form extremely tight intertwined dimers that rely on the nonclassical hydrophobic effect for their stability. Smaller clips and tweezers with a simple benzene bridge remain monomeric in buffered aqueous solution and display a complementary binding profile. While the clips with parallel sidewalls prefer flat aromatic cations such as pyridinium salts, the torus-shaped tweezers bind to basic amino acids lysine and arginine via a threading process. These mutually exclusive binding modes make water-soluble clips and tweezers valuable tools for probing critical biological interactions with positively charged amino acid side chains and cofactors.Molecular clips and tweezers can be employed for the complete inhibition of dehydrogenases. The clip extracts NAD+ from its Rossman fold, while the tweezer complexes access strategic lysine residues around the active site. Our new enzyme inhibitors recognize the protein surface and thus offer additional targets for medicinal chemistry. Finally, the ability of molecular tweezers to cap critical lysine residues can be used to interfere with the pathology of protein misfolding diseases such as Alzheimer's disease, because many of them involve noncovalent interactions with these critical residues during their early stages. When the key protein produces a β-sheet-rich nucleus, this structure undergoes spontaneous polymerization into highly toxic oligomers, ultimately leading to mature fibrils. The benzene-spaced phosphate tweezer forms a specific complex with lysine residues 16 and 28 in Aβ42 and thus prevents the formation of misfolded oligomers rich in β-sheets. This entirely new process-specific mechanism that prevents pathologic protein aggregation also operates in many other related amyloidogenic proteins. © 2012 American Chemical Society.
    view abstractdoi: 10.1021/ar300061c
  • 2013 • 228 Elastometry of deflated capsules: Elastic moduli from shape and wrinkle analysis
    Knoche, S. and Vella, D. and Aumaitre, E. and Degen, P. and Rehage, H. and Cicuta, P. and Kierfeld, J.
    Langmuir 29 12463-12471 (2013)
    Elastic capsules, prepared from droplets or bubbles attached to a capillary (as in a pendant drop tensiometer), can be deflated by suction through the capillary. We study this deflation and show that a combined analysis of the shape and wrinkling characteristics enables us to determine the elastic properties in situ. Shape contours are analyzed and fitted using shape equations derived from nonlinear membrane-shell theory to give the elastic modulus, Poisson ratio and stress distribution of the membrane. We include wrinkles, which generically form upon deflation, within the shape analysis. Measuring the wavelength of wrinkles and using the calculated stress distribution gives the bending stiffness of the membrane. We compare this method with previous approaches using the Laplace-Young equation and illustrate the method on two very different capsule materials: polymerized octadecyltrichlorosilane (OTS) capsules and hydrophobin (HFBII) coated bubbles. Our results are in agreement with the available rheological data. For hydrophobin coated bubbles, the method reveals an interesting nonlinear behavior consistent with the hydrophobin molecules having a rigid core surrounded by a softer shell. © 2013 American Chemical Society.
    view abstractdoi: 10.1021/la402322g
  • 2013 • 227 Analysis of particle kinematics in spheronization via particle image velocimetry
    Koester, M. and Thommes, M.
    European Journal of Pharmaceutics and Biopharmaceutics 83 307-314 (2013)
    Spheronization is a wide spread technique in pellet production for many pharmaceutical applications. Pellets produced by spheronization are characterized by a particularly spherical shape and narrow size distribution. The particle kinematic during spheronization is currently not well-understood. Therefore, particle image velocimetry (PIV) was implemented in the spheronization process to visualize the particle movement and to identify flow patterns, in order to explain the influence of various process parameters. The spheronization process of a common formulation was recorded with a high-speed camera, and the images were processed using particle image velocimetry software. A crosscorrelation approach was chosen to determine the particle velocity at the surface of the pellet bulk. Formulation and process parameters were varied systematically, and their influence on the particle velocity was investigated. The particle stream shows a torus-like shape with a twisted rope-like motion. It is remarkable that the overall particle velocity is approximately 10-fold lower than the tip speed of the friction plate. The velocity of the particle stream can be correlated to the water content of the pellets and the load of the spheronizer, while the rotation speed was not relevant. In conclusion, PIV was successfully applied to the spheronization process, and new insights into the particle velocity were obtained. © 2012 Elsevier B.V. All rights reserved.
    view abstractdoi: 10.1016/j.ejpb.2012.08.013
  • 2013 • 226 Combination of a photosystem 1-based photocathode and a photosystem 2-based photoanode to a z-scheme mimic for biophotovoltaic applications
    Kothe, T. and Plumeré, N. and Badura, A. and Nowaczyk, M.M. and Guschin, D.A. and Rögner, M. and Schuhmann, W.
    Angewandte Chemie - International Edition 52 14233-14236 (2013)
    Z-Scheme on wires: The two photosystems of the natural photosynthetic Z-scheme have been connected by immobilizing them within redox hydrogels on individual electrodes. Upon irradiation, this biophotovoltaic device produced photocurrents as a closed and autonomous system. The open-circuit voltage of the cell corresponds to the potential difference between the two redox hydrogels and indicates the coupling of the two charge separation steps. © 2013 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
    view abstractdoi: 10.1002/anie.201303671
  • 2013 • 225 Effect of microformulation on the bioactivity of an anthocyanin-rich bilberry pomace extract (Vaccinium myrtillus L.) in vitro
    Kropat, C. and Betz, M. and Kulozik, U. and Leick, S. and Rehage, H. and Boettler, U. and Teller, N. and Marko, D.
    Journal of Agricultural and Food Chemistry 61 4873-4881 (2013)
    In cell culture were compared the different release rates of anthocyanins from a bilberry pomace extract encapsulated either in food grade whey protein-based matrix capsules (WPC) or in pectin amid-based hollow spherical capsules (PHS). The impact of the formulations on typical anthocyanin-associated biological end points such as inhibition of the epidermal growth factor receptor (EGFR) and suppression of cell growth in HT29 colon carcinoma cells was assessed. The purpose was to find whether the release rates are sufficient to maintain biological activity and whether encapsulation affected EGFR inhibitory and growth suppressive properties of the extract. Even though anthocyanin release from extract-loaded capsules was proven under cell culture conditions, the inhibitory potential toward the EGFR was diminished. However, nonencapsulated extract as well as both extract-loaded encapsulation systems diminished the growth of HT29 cells to a comparable extent. The loss of EGFR inhibitory properties by encapsulation despite anthocyanin release indicates substantial contribution of other further constituents not monitored so far. Taken together, both applied encapsulation strategies allowed anthocyanin release and maintained biological activity with respect to growth inhibitory properties. However, the loss of EGFR inhibitory effects emphasizes the need for biological profiling to estimate process-induced changes of plant constituent's beneficial potencies. © 2013 American Chemical Society.
    view abstractdoi: 10.1021/jf305180j
  • 2013 • 224 Bifurcation of velocity distributions in cooperative transport of filaments by fast and slow motors
    Li, X. and Lipowsky, R. and Kierfeld, J.
    Biophysical Journal 104 666-676 (2013)
    Several intracellular processes are governed by two different species of molecular motors, fast and slow ones, that both move in the same direction along the filaments but with different velocities. The transport of filaments arising from the cooperative action of these motors has been recently studied by three in vitro experiments, in which the filament velocity was measured for varying fraction of the fast motors adsorbed onto substrate surfaces in a gliding assay. As the fast motor fraction was increased, two experiments found a smooth change whereas the third one observed an abrupt increase of the filament velocity. Here, we show that all of these experimental results reflect the competition between fast and slow motors and can be understood in terms of an underlying saddle-node bifurcation. The comparison between theory and experiment leads to predictions for the detachment forces of the two motor species. Our theoretical study shows the existence of three different motility regimes: 1), fast transport with a single velocity; 2), slow transport with a single velocity; and 3), bistable transport, where the filament velocity stochastically switches between fast and slow transport. We determine the parameter regions for these regimes in terms of motility diagrams as a function of the surface fraction of fast motors and microscopic single-motor parameters. An abrupt increase of the filament velocity for an increasing fraction of fast motors is associated with the occurrence of bistable transport. © 2013 Biophysical Society.
    view abstractdoi: 10.1016/j.bpj.2012.11.3834
  • 2013 • 223 CoCrMo metal-on-metal hip replacements
    Liao, Y. and Hoffman, E. and Wimmer, M. and Fischer, A. and Jacobs, J. and Marks, L.
    Physical Chemistry Chemical Physics 15 746-756 (2013)
    After the rapid growth in the use of CoCrMo metal-on-metal hip replacements since the second generation was introduced circa 1990, metal-on-metal hip replacements have experienced a sharp decline in the last two years due to biocompatibility issues related to wear and corrosion products. Despite some excellent clinical results, the release of wear and corrosion debris and the adverse response of local tissues have been of great concern. There are many unknowns regarding how CoCrMo metal bearings interact with the human body. This perspective article is intended to outline some recent progresses in understanding wear and corrosion of metal-on-metal hip replacement both in vivo and in vitro. The materials, mechanical deformation, corrosion, wear-assisted corrosion, and wear products will be discussed. Possible adverse health effects caused by wear products will be briefly addressed, as well as some of the many open questions such as the detailed chemistry of corrosion, tribochemical reactions and the formation of graphitic layers. Nowadays we design almost routinely for high performance materials and lubricants for automobiles; humans are at least as important. It is worth remembering that a hip implant is often the difference between walking and leading a relatively normal life, and a wheelchair. © 2013 the Owner Societies.
    view abstractdoi: 10.1039/c2cp42968c
  • 2013 • 222 Iron metal-organic frameworks MIL-88B and NH2-MIL-88B for the loading and delivery of the gasotransmitter carbon monoxide
    Ma, M. and Noei, H. and Mienert, B. and Niesel, J. and Bill, E. and Muhler, M. and Fischer, R.A. and Wang, Y. and Schatzschneider, U. and Metzler-Nolte, N.
    Chemistry - A European Journal 19 6785-6790 (2013)
    Crystals of MIL-88B-Fe and NH2-MIL-88B-Fe were prepared by a new rapid microwave-assisted solvothermal method. High-purity, spindle-shaped crystals of MIL-88B-Fe with a length of about 2 μm and a diameter of 1 μm and needle-shaped crystals of NH2-MIL-88B-Fe with a length of about 1.5 μm and a diameter of 300 nm were produced with uniform size and excellent crystallinity. The possibility to reduce the as-prepared frameworks and the chemical capture of carbon monoxide in these materials was studied by in situ ultrahigh vacuum Fourier-transform infrared (UHV-FTIR) spectroscopy and Mössbauer spectroscopy. CO binding occurs to unsaturated coordination sites (CUS). The release of CO from the as-prepared materials was studied by a myoglobin assay in physiological buffer. The release of CO from crystals of MIL-88B-Fe with t1/2=38 min and from crystals of NH 2-MIL-88B-Fe with t1/2=76 min were found to be controlled by the degradation of the MIL materials under physiological conditions. These MIL-88B-Fe and NH2-MIL-88B-Fe materials show good biocompatibility and have the potential to be used in pharmacological and therapeutic applications as carriers and delivery vehicles for the gasotransmitter carbon monoxide. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/chem.201201743
  • 2013 • 221 Highly soluble energy relay dyes for dye-sensitized solar cells
    Margulis, G.Y. and Lim, B. and Hardin, B.E. and Unger, E.L. and Yum, J.-H. and Feckl, J.M. and Fattakhova-Rohlfing, D. and Bein, T. and Grätzel, M. and Sellinger, A. and McGehee, M.D.
    Physical Chemistry Chemical Physics 15 11306-11312 (2013)
    High solubility is a requirement for energy relay dyes (ERDs) to absorb a large portion of incident light and significantly improve the efficiency of dye-sensitized solar cells (DSSCs). Two benzonitrile-soluble ERDs, BL302 and BL315, were synthesized, characterized, and resulted in a 65% increase in the efficiency of TT1-sensitized DSSCs. The high solubility (180 mM) of these ERDs allows for absorption of over 95% of incident light at their peak wavelength. The overall power conversion efficiency of DSSCs with BL302 and BL315 was found to be limited by their energy transfer efficiency of approximately 70%. Losses due to large pore size, dynamic collisional quenching of the ERD, energy transfer to desorbed sensitizing dyes and static quenching by complex formation were investigated and it was found that a majority of the losses are caused by the formation of statically quenched ERDs in solution. © 2013 the Owner Societies.
    view abstractdoi: 10.1039/c3cp51018b
  • 2013 • 220 Solid dispersions prepared by continuous cogrinding in an air jet mill
    Muehlenfeld, C. and Kann, B. and Windbergs, M. and Thommes, M.
    Journal of Pharmaceutical Sciences 102 4132-4139 (2013)
    Embedding a poorly water-soluble drug as a solid dispersion in a hydrophilic carrier by cogrinding is a possible strategy for enhancing the drug dissolution rate. Although general interest in continuous processes for manufacturing drug formulations has increased, many publications still focus on batch processes. The jet mill used in this study is a promising tool for continuous cogrinding. Investigation of different drug-to-carrier ratios (griseofulvin/mannitol) demonstrated that a drug load of 10% is best suited to investigate the enhanced dissolution behavior. To gain deeper insight into the underlying mechanisms, the coground dispersion is compared with different physical mixtures in terms of physicochemical properties and dissolution behavior. Differential scanning calorimetry and X-ray powder diffraction were used to verify the crystalline structure of the coground formulation. On the basis of the Hixson-Crowell model, particle size reduction was ruled out as the main reason for dissolution enhancement. An increase of surface free energies because of grinding is shown with contact angle measurements. Confocal Raman microscopy investigations revealed the drug's bulk dispersity in the coground formulation as an additional factor for the increased dissolution rate. In conclusion, the continuous cogrinding approach is a promising technique to prepare the drug in a rapidly dissolving, yet crystalline, form. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.
    view abstractdoi: 10.1002/jps.23731
  • 2013 • 219 Hofmeister effect of sodium halides on the switching energetics of thermoresponsive polymer brushes
    Naini, C.A. and Thomas, M. and Franzka, S. and Frost, S. and Ulbricht, M. and Hartmann, N.
    Macromolecular Rapid Communications 34 417-422 (2013)
    A laser temperature-jump technique is used to probe the impact of sodium halides on the temperature-dependent switching kinetics and thermodynamics of poly(N-isopropylacrylamide) brushes. An analysis on the basis of a two-state model reveals van't Hoff enthalpy and entropy changes. Sodium halides increase the endothermicity and the entropic gain of the switching process below and above Tc following the Hofmeister series: NaCl &gt; NaBr &gt; NaI. In contrast, enthalpic and entropic changes at Tc remain virtually unaffected. This provides an unprecedented insight into the underlying switching energetics of this classic stimuli-responsive polymer. Because of its model character, these results represent an essential reference on the way to unpuzzle the molecular driving forces of the Hofmeister effect. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/marc.201200681
  • 2013 • 218 Design and fabrication of a bending rotation fatigue test rig for in situ electrochemical analysis during fatigue testing of NiTi shape memory alloy wires
    Neelakantan, L. and Zglinski, J.K. and Frotscher, M. and Eggeler, G.
    Review of Scientific Instruments 84 (2013)
    The current investigation proposes a novel method for simultaneous assessment of the electrochemical and structural fatigue properties of nickel-titanium shape memory alloy (NiTi SMA) wires. The design and layout of an in situ electrochemical cell in a custom-made bending rotation fatigue (BRF) test rig is presented. This newly designed test rig allows performing a wide spectrum of experiments for studying the influence of fatigue on corrosion and vice versa. This can be achieved by performing ex situ andor in situ measurements. The versatility of the combined electrochemicalmechanical test rig is demonstrated by studying the electrochemical behavior of NiTi SMA wires in 0.9 NaCl electrolyte under load. The ex situ measurements allow addressing various issues, for example, the influence of pre-fatigue on the localized corrosion resistance, or the influence of hydrogen on fatigue life. Ex situ experiments showed that a pre-fatigued wire is more susceptible to localized corrosion. The synergetic effect can be concluded from the polarization studies and specifically from an in situ study of the open circuit potential (OCP) transients, which sensitively react to the elementary repassivation events related to the local failure of the oxide layer. It can also be used as an indicator for identifying the onset of the fatigue failure. © 2013 American Institute of Physics.
    view abstractdoi: 10.1063/1.4793488
  • 2013 • 217 Small-angle water reorientations in KOH doped hexagonal ice and clathrate hydrates
    Nelson, H. and Schildmann, S. and Nowaczyk, A. and Gainaru, C. and Geil, B. and Böhmer, R.
    Physical Chemistry Chemical Physics 15 6355-6367 (2013)
    Using deuteron nuclear magnetic resonance and dielectric spectroscopy KOH doped tetrahydrofuran clathrate hydrates and KOH doped hexagonal ice are studied at temperatures above 60 and 72 K, respectively. Below these temperatures proton order is established on the lattice formed by the water molecules. In the clathrate hydrate a new type of small-angle motion is discovered using deuteron spin-spin relaxation, line-shape analysis, and stimulated-echo experiments. Based on the latter results a model is developed for the local proton motion that could successfully be tested using random-walk simulations. It is argued that the newly identified small-angle motion, obviously absent in undoped samples, is an important feature of the mechanism which accompanies the establishment of proton order not only in doped clathrate hydrates but also in doped hexagonal ice. Specific motions of OH- defects are demonstrated to explain the experimentally observed behavior. The relative importance of localized versus delocalized OH- defect motions is discussed. © 2013 the Owner Societies.
    view abstractdoi: 10.1039/c3cp00139c
  • 2013 • 216 Natural-product-derived fragments for fragment-based ligand discovery
    Over, B. and Wetzel, S. and Grütter, C. and Nakai, Y. and Renner, S. and Rauh, D. and Waldmann, H.
    Nature Chemistry 5 21-28 (2013)
    Fragment-based ligand and drug discovery predominantly employs sp 2 -rich compounds covering well-explored regions of chemical space. Despite the ease with which such fragments can be coupled, this focus on flat compounds is widely cited as contributing to the attrition rate of the drug discovery process. In contrast, biologically validated natural products are rich in stereogenic centres and populate areas of chemical space not occupied by average synthetic molecules. Here, we have analysed more than 180,000 natural product structures to arrive at 2,000 clusters of natural-product-derived fragments with high structural diversity, which resemble natural scaffolds and are rich in sp 3 -configured centres. The structures of the cluster centres differ from previously explored fragment libraries, but for nearly half of the clusters representative members are commercially available. We validate their usefulness for the discovery of novel ligand and inhibitor types by means of protein X-ray crystallography and the identification of novel stabilizers of inactive conformations of p38α MAP kinase and of inhibitors of several phosphatases. © 2013 Macmillan Publishers Limited. All rights reserved.
    view abstractdoi: 10.1038/nchem.1506
  • 2013 • 215 Ab Initio Based conformational study of the crystalline α-chitin
    Petrov, M. and Lymperakis, L. and Friák, M. and Neugebauer, J.
    Biopolymers 99 22-34 (2013)
    The equilibrium structure including the network of hydrogen bonds of an α-chitin crystal is determined combining density-functional theory (DFT), self-consistent DFT-based tight-binding (SCC-DFTB), and empirical forcefield molecular dynamics (MD) simulations. Based on the equilibrium geometry several possible crystal conformations (local energy minima) have been identified and related to hydrogen bond patterns. Our results provide new insight and allow to resolve the contradicting α-chitin structural models proposed by various experiments. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.
    view abstractdoi: 10.1002/bip.22131
  • 2013 • 214 Why silver deposition is so fast: Solving the enigma of metal deposition
    Pinto, L.M.C. and Spohr, E. and Quaino, P. and Santos, E. and Schmickler, W.
    Angewandte Chemie - International Edition 52 7883-7885 (2013)
    A perfect match: Silver deposition is one of the fastest electrochemical reactions, even though the Ag+ ion loses more than 5 eV solvation energy in the process. This phenomenon, an example of the enigma of metal deposition, was investigated by a combination of MD simulations, DFT, and specially developed theory. At the surface, the Ag+ ion experiences a strong interaction with the sp band of silver, which catalyzes the reaction. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201301998
  • 2013 • 213 Solvent-sensitive reversible stress-response of shape memory natural rubber
    Quitmann, D. and Gushterov, N. and Sadowski, G. and Katzenberg, F. and Tiller, J.C.
    ACS Applied Materials and Interfaces 5 3504-3507 (2013)
    We found that constrained shape memory natural rubber (SMNR) generates mechanical stress when exposed to solvent vapor. When the solvent vapor is removed, the material reprograms itself. This process is reversible and the stress answer is proportional to the solvent vapor concentration. Further, the stress answer is specific to the solvent. © 2013 American Chemical Society.
    view abstractdoi: 10.1021/am400660f
  • 2013 • 212 Size control of laser-fabricated surfactant-free gold nanoparticles with highly diluted electrolytes and their subsequent bioconjugation
    Rehbock, C. and Merk, V. and Gamrad, L. and Streubel, R. and Barcikowski, S.
    Physical Chemistry Chemical Physics 15 3057-3067 (2013)
    Size control of laser-fabricated surfactant-free gold nanoparticles is a challenging endeavor. In this work, we show that size control can be achieved by adding ions with low salinity during synthesis. In addition, this approach offers the opportunity to fundamentally study ion interactions with bare nanoparticle surfaces and can help to elucidate the nanoparticle formation mechanism. The studies were carried out in a flow-through reactor and in the presence of NaCl, NaBr and sodium phosphate buffer at minimal ionic strengths. A significant size quenching effect at ionic strengths from 1-50 μM was found, which allowed surfactant-free nanoparticle size control with average diameters of 6-30 nm. This effect went along with low polydispersity and minimal aggregation tendencies and was confirmed by UV-vis spectroscopy, TEM, SEM and analytical disk centrifugation. Our findings indicate that size quenching originates from an anionic electrostatic stabilization depending on the nanoparticle surface area, which may be caused by specific ion adsorption. By subsequent delayed bioconjugation in liquid-flow using bovine serum albumin as a stabilizing agent, nano-bioconjugates with good stability in cell culture media were obtained, which are applicable in toxicology and cell biology. This journal is © 2013 the Owner Societies.
    view abstractdoi: 10.1039/c2cp42641b
  • 2013 • 211 Solid crystal suspensions containing griseofulvin-Preparation and bioavailability testing
    Reitz, E. and Vervaet, C. and Neubert, R.H.H. and Thommes, M.
    European Journal of Pharmaceutics and Biopharmaceutics 83 193-202 (2013)
    The improvement of the bioavailability of poorly soluble drugs has been an important issue in pharmaceutical research for many years. Despite the suggestion of several other technologies in the past, drug particle size reduction is still an appropriate strategy to guarantee high bioavailability of various drugs. A few years ago, the Solid Crystal Suspension (SCS) technology was suggested, in which crystalline drug particles are ground and dispersed in a highly soluble crystalline carrier by a hot melt extrusion process. The current study demonstrates the scale-up of the SCS technology to standard, lab-scale extrusion equipment - a change from previous investigations, which used small batch sizes. A twin-screw extruder was modified to account for the rapid crystallization of the carrier. The screw speed and the barrel temperature were identified as critical process parameters and were varied systematically in several experimental designs. Finally, parameters were identified that produced extrudates with rapid dissolution rates. After extrusion, the extrudates were milled to granules and then tableted. These tablets were investigated with respect to their bioavailability in beagle dogs. It was found that drug particle size reduction in the hot melt extrusion led to 3.5-fold higher bioavailability in these dogs than occurred with the physical mixture of the used substances. The solid crystal suspension formulation had a slightly higher bioavailability than the marked product. In conclusion, the SCS technology was successfully scaled up to lab-scale equipment, and the concept was confirmed by a bioavailability study. © 2012 Elsevier B.V. All rights reserved.
    view abstractdoi: 10.1016/j.ejpb.2012.09.012
  • 2013 • 210 Surface grafting of Corchorus olitorius fibre: A green approach for the development of activated bioadsorbent
    Roy, A. and Chakraborty, S. and Kundu, S.P. and Majumder, S.B. and Adhikari, B.
    Carbohydrate Polymers 92 2118-2127 (2013)
    The present work is an endeavor to prepare lignocellulosic biomass based adsorbent, suitable for removal of organic and inorganic pollutants from industrial effluents. Lignocellulosic Corchorus olitorius fibre (jute fibre) surface was grafted with naturally available polyphenol, tannin, preceded by the epoxy-activation of fibre surface with epichlorohydrin under mild condition in an aqueous suspension. The reaction parameters for the modification, viz., concentration of epichlorohydrin and tannin, time, and temperature were optimized. The successful occurrence of surface modification of jute fibre (JF) was characterized and estimated from weight gain percent, elemental analysis, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, scanning electron and atomic force microscopy, and thermogravimetric analysis. An extensive analysis of deconvoluted FTIR spectra using the Voigt model was utilized to ensure the surface grafting. The microbiological susceptibility study revealed high persistency of JF towards biodegradation after efficient grafting with tannin. © 2012 Elsevier Ltd.
    view abstractdoi: 10.1016/j.carbpol.2012.11.039
  • 2013 • 209 Influence of janus particle shape on their interfacial behavior at liquid-liquid interfaces
    Ruhland, T.M. and Gröschel, A.H. and Ballard, N. and Skelhon, T.S. and Walther, A. and Müller, A.H.E. and Bon, S.A.F.
    Langmuir 29 1388-1394 (2013)
    We investigate the self-Assembly behavior of Janus particles with different geometries at a liquid-liquid interface. The Janus particles we focus on are characterized by a phase separation along their major axis into two hemicylinders of different wettability. We present a combination of experimental and simulation data together with detailed studies elucidating the mechanisms governing the adsorption process of Janus spheres, Janus cylinders, and Janus discs. Using the pendant drop technique, we monitor the assembly kinetics following changes in the interfacial tension of nanoparticle adsorption. According to the evolution of the interfacial tension and simulation data, we will specify the characteristics of early to late stages of the Janus particle adsorption and discuss the effect of Janus particle shape and geometry. The adsorption is characterized by three adsorption stages which are based on the different assembly kinetics and different adsorption mechanisms depending on the particle shape. © 2013 American Chemical Society.
    view abstractdoi: 10.1021/la3048642
  • 2013 • 208 Rapid immuno-SERS microscopy for tissue imaging with single-nanoparticle sensitivity
    Salehi, M. and Steinigeweg, D. and Ströbel, P. and Marx, A. and Packeisen, J. and Schlücker, S.
    Journal of Biophotonics 6 785-792 (2013)
    Immuno-SERS microscopy is a novel imaging technique in nano-biophotonics, which employs antibodies labeled with SERS-active nanoparticles in conjunction with Raman microscopy. Rapid data acquisition is of central importance for screening large areas of tissue specimens. Here, we first discuss the role of SERS labels with single-particle sensitivity in immuno-SERS microscopy, in particular with respect to false-negative results. In combined single-particle experiments (SERS microscopy/dark-field microscopy/HR-SEM), we then demonstrate that small glass-coated clusters (dimers and trimers) of gold nanospheres exhibit the desired single-particle SERS sensitivity, even at acquisition times as short as 30 msec per pixel, while monomers do not. The proof-of-concept for rapid immuno-SERS microscopy with 30 msec acquisition time per pixel for selective imaging of the p53 family member p63 in prostate tissue sections is demonstrated. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/jbio.201200148
  • 2013 • 207 Ab initio prediction of the critical thickness of a precipitate
    Sampath, S. and Janisch, R.
    Journal of Physics Condensed Matter 25 (2013)
    Segregation and precipitation of second phases in metals and metallic alloys is an important phenomenon that has a strong influence on the mechanical properties of the material. Models exist that describe the growth of coherent, semi-coherent and incoherent precipitates. One important parameter of these models is the energy of the interface between matrix and precipitate. In this work we apply ab initio density functional theory calculations to obtain this parameter and to understand how it depends on chemical composition and mechanical strain at the interface. Our example is a metastable Mo-C phase, the body-centred tetragonal structure, which exists as a semi-coherent precipitate in body-centred cubic molybdenum. The interface of this precipitate is supposed to change from coherent to semi-coherent during the growth of the precipitate. We predict the critical thickness of the precipitate by calculating the different contributions to a semi-coherent interface energy by means of ab initio density functional theory calculations. The parameters in our model include the elastic strain energy stored in the precipitate, as well as a misfit dislocation energy that depends on the dislocation core width and the dislocation spacing. Our predicted critical thickness agrees well with experimental observations. © 2013 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0953-8984/25/35/355005
  • 2013 • 206 Surface anchored metal-organic frameworks as stimulus responsive antifouling coatings
    Sancet, M.P.A. and Hanke, M. and Wang, Z. and Bauer, S. and Azucena, C. and Arslan, H.K. and Heinle, M. and Gliemann, H. and Wöll, C. and Rosenhahn, A.
    Biointerphases 8 (2013)
    Surface-anchored, crystalline and oriented metal organic frameworks (SURMOFs) have huge potential for biological applications due to their well-defined and highly-porous structure. In this work we describe a MOF-based, fully autonomous system, which combines sensing, a specific response, and the release of an antimicrobial agent. The Cu-containing SURMOF, Cu-SURMOF 2, is stable in artificial seawater and shows stimulus-responsive anti-fouling properties against marine bacteria. When Cobetia marina adheres on the SURMOF, the framework's response is lethal to the adhering microorganism. A thorough analysis reveals that this response is induced by agents secreted from the microbes after adhesion to the substrate, and includes a release of Cu ions resulting from a degradation of the SURMOF. The stimulus-responsive antifouling effect of Cu-SURMOF 2 demonstrates the first application of Cu-SURMOF 2 as autonomous system with great potential for further microbiological and cell culture applications. © 2013 Arpa Sancet et al.
    view abstractdoi: 10.1186/1559-4106-8-29
  • 2013 • 205 Picosecond opto-acoustic interferometry and polarimetry in high-index GaAs
    Scherbakov, A.V. and Bombeck, M. and Jäger, J.V. and Salasyuk, A.S. and Linnik, T.L. and Gusev, V.E. and Yakovlev, D.R. and Akimov, A.V. and Bayer, M.
    Optics Express 21 16473-16485 (2013)
    By means of a metal opto-acoustic transducer we generate quasilongitudinal and quasi-transverse picosecond strain pulses in a (311)-GaAs substrate and monitor their propagation by picosecond acoustic interferometry. By probing at the sample side opposite to the transducer the signals related to the compressive and shear strain pulses can be separated in time. In addition to conventional monitoring of the reflected probe light intensity we monitor also the polarization rotation of the optical probe beam. This polarimetric technique results in improved sensitivity of detection and provides comprehensive information about the elasto-optical anisotropy. The experimental observations are in a good agreement with a theoretical analysis. © 2013 Optical Society of America.
    view abstractdoi: 10.1364/OE.21.016473
  • 2013 • 204 Single gold trimers and 3D superstructures exhibit a polarization- independent SERS response
    Steinigeweg, D. and Schütz, M. and Schlücker, S.
    Nanoscale 5 110-113 (2013)
    Dimers of metal nanospheres are well-known for their characteristic anisotropic optical response. Here, we demonstrate in single-particle SERS experiments that individual gold trimers and 3D superstructures exhibit a polarization-independent SERS response. This optical behavior of single particle clusters provides constant SERS signals, independent of the mutual orientation of the incident laser polarization and the plasmonic nanostructure, which is desired or even required in many SERS applications. © 2013 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c2nr31982a
  • 2013 • 203 Fabrication of Borassus fruit lignocellulose fiber/PP composites and comparison with jute, sisal and coir fibers
    Sudhakara, P. and Jagadeesh, D. and Wang, Y. and Venkata Prasad, C. and Devi, A.P.K. and Balakrishnan, G. and Kim, B.S. and Song, J.I.
    Carbohydrate Polymers 98 1002-1010 (2013)
    Novel composites based on borassus fruit fine fiber (BFF) and polypropylene (PP) were fabricated with variable fiber composition (5, 10, 15 and 20 wt%) by injection molding. Maleated PP (MAPP) was also used as compatibilizer at 5 wt% for effective fiber-matrix adhesion. FTIR analysis confirms the evidence of a chemical bonding between the fiber and polymeric matrix through esterification in presence of MAPP. The tensile and flexural properties were found to increase with 15 and 10 wt% fiber loadings respectively, and decreased thereafter. Coir, jute and sisal fiber composites were also fabricated with 15 wt% fiber loading under the same conditions as used for BFF/PP composites. It was found that the mechanical properties of BFF (15 wt%)/PP composites were equivalent to jute/PP, sisal/PP and superior to coir/PP composites. Jute/PP and sisal/PP composites showed higher water absorption than BFF/PP and coir/PP composites. These results have demonstrated that the BFF/PP composites can also be an alternative material for composites applications. © 2013 Elsevier Ltd. All rights reserved.
    view abstractdoi: 10.1016/j.carbpol.2013.06.080
  • 2013 • 202 Electrochemical detection of chloride levels in sweat using silver nanoparticles: A basis for the preliminary screening for cystic fibrosis
    Toh, H.S. and Batchelor-Mcauley, C. and Tschulik, K. and Compton, R.G.
    Analyst 138 4292-4297 (2013)
    Cystic fibrosis is a common disease which has an associated characteristic symptom of high sweat chloride content. Thus, chloride ion quantification in sweat is important towards the screening of cystic fibrosis. Electrochemical methods, being cost effective and convenient, can be exploited for this. The electrochemical oxidation of silver nanoparticles in the absence of chloride ions gives one voltammetric signal related to the oxidation of silver to silver ions. The presence of chloride ions in the solution causes the appearance of an additional signal at a lower potential which is related to the oxidation of silver to silver chloride. This signal has a peak height which correlates linearly with the concentration of chloride ions from 2 mM to 40 mM when the electrochemical experiments are performed on silver nanoparticle modified screen printed electrodes. Thus, reliable quantification was found to be achievable. Furthermore, chloride ion levels of diluted synthetic sweat samples are measured accurately with the modified electrodes. Thus, the detection of the chloride ion concentration with a silver nanoparticle modified electrode provides a proof-of-concept for a point-of-care system for preliminary screening of cystic fibrosis. © 2013 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c3an00843f
  • 2013 • 201 The anodic stripping voltammetry of nanoparticles: Electrochemical evidence for the surface agglomeration of silver nanoparticles
    Toh, H.S. and Batchelor-McAuley, C. and Tschulik, K. and Uhlemann, M. and Crossley, A. and Compton, R.G.
    Nanoscale 5 4884-4893 (2013)
    Analytical expressions for the anodic stripping voltammetry of metallic nanoparticles from an electrode are provided. First, for reversible electron transfer, two limits are studied: that of diffusionally independent nanoparticles and the regime where the diffusion layers originating from each particle overlap strongly. Second, an analytical expression for the voltammetric response under conditions of irreversible electron transfer kinetics is also derived. These equations demonstrate how the peak potential for the stripping process is expected to occur at values negative of the formal potential for the redox process in which the surface immobilised nanoparticles are oxidised to the corresponding metal cation in the solution phase. This work is further developed by considering the surface energies of the nanoparticles and its effect on the formal potential for the oxidation. The change in the formal potential is modelled in accordance with the equations provided by Plieth [J. Phys. Chem., 1982, 86, 3166-3170]. The new analytical expressions are used to investigate the stripping of silver nanoparticles from a glassy carbon electrode. The relative invariance of the stripping peak potential at low surface coverages of silver is shown to be directly related to the surface agglomeration of the nanoparticles. © 2013 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c3nr00898c
  • 2013 • 200 'Sticky electrodes' for the detection of silver nanoparticles
    Tschulik, K. and Palgrave, R.G. and Batchelor-Mcauley, C. and Compton, R.G.
    Nanotechnology 24 (2013)
    Detection and quantification of nanoparticles in environmental systems is a task that requires reliable and affordable analytical methods. Here an approach using a cysteine-modified 'sticky' glassy carbon electrode is presented. The electrode is immersed in a silver nanoparticle containing electrolyte and left in this suspension without an applied potential, i.e. under open circuit condition, for a variable amount of time. The amount of silver nanoparticles immobilized on the electrode within this sticking time is then determined by oxidative stripping, yielding the anodic charge and thus the amount of Ag nanoparticles sticking to the electrode surface. When using a cysteine-modified glassy carbon electrode, significant and reproducible amounts of silver nanoparticles stick to the surface, which is not the case for unmodified glassy carbon surfaces. Additionally, proof-of-concept experiments are performed on real seawater samples. These demonstrate that also under simulated environmental conditions an increased immobilization and hence improved detection of silver nanoparticles on cysteine-modified glassy carbon electrodes is achieved, while no inhibitive interference with this complex matrix is observed. © 2013 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0957-4484/24/29/295502
  • 2013 • 199 De Novo design of protein kinase inhibitors by in silico identification of hinge region-binding fragments
    Urich, R. and Wishart, G. and Kiczun, M. and Richters, A. and Tidten-Luksch, N. and Rauh, D. and Sherborne, B. and Wyatt, P.G. and Brenk, R.
    ACS Chemical Biology 8 1044-1052 (2013)
    Protein kinases constitute an attractive family of enzyme targets with high relevance to cell and disease biology. Small molecule inhibitors are powerful tools to dissect and elucidate the function of kinases in chemical biology research and to serve as potential starting points for drug discovery. However, the discovery and development of novel inhibitors remains challenging. Here, we describe a structure-based de novo design approach that generates novel, hinge-binding fragments that are synthetically feasible and can be elaborated to small molecule libraries. Starting from commercially available compounds, core fragments were extracted, filtered for pharmacophoric properties compatible with hinge-region binding, and docked into a panel of protein kinases. Fragments with a high consensus score were subsequently short-listed for synthesis. Application of this strategy led to a number of core fragments with no previously reported activity against kinases. Small libraries around the core fragments were synthesized, and representative compounds were tested against a large panel of protein kinases and subjected to co-crystallization experiments. Each of the tested compounds was active against at least one kinase, but not all kinases in the panel were inhibited. A number of compounds showed high ligand efficiencies for therapeutically relevant kinases; among them were MAPKAP-K3, SRPK1, SGK1, TAK1, and GCK for which only few inhibitors are reported in the literature. © 2013 American Chemical Society.
    view abstractdoi: 10.1021/cb300729y
  • 2013 • 198 Communication: Substrate induced dehydrogenation: Transformation of octa-ethyl-porphyrin into tetra-benzo-porphyrin
    Van Vörden, D. and Lange, M. and Schmuck, M. and Schaffert, J. and Cottin, M.C. and Bobisch, C.A. and Möller, R.
    Journal of Chemical Physics 138 (2013)
    Individual molecules of octa-ethyl-porhphyrin-iron(III)-chloride adsorbed on a Cu(111) surface are studied by scanning tunneling microscopy. Upon moderate heating the molecules are found to transform into Fe-tetra-benzo-porphyrin at a surprisingly low temperature of 380 K. If the annealing is interrupted, the different steps of the transformation can be imaged. By evaluating the ratio of transformed molecules as function of annealing temperature, an approximate activation energy of 1.2 eV ± 0.1 eV could be determined. © 2013 AIP Publishing LLC.
    view abstractdoi: 10.1063/1.4810879
  • 2013 • 197 TiO2(B)/anatase composites synthesized by spray drying as high performance negative electrode material in Li-ion batteries
    Ventosa, E. and Mei, B. and Xia, W. and Muhler, M. and Schuhmann, W.
    ChemSusChem 6 1312-1315 (2013)
    The power of spray-dried TiO2 in LIBs: TiO2(B)/ anatase is synthesized by spray drying and investigated as negative electrode material in Li-ion batteries. It exhibits excellent Li-ion storage performances, especially at high charge/discharge rates. The presence of the β phase of TiO2 improves Li-ion diffusivity. Additionally, the scalable synthesis method also allows for Nb-doping, which assists in the maintenance of the electronic conductivity as the thickness of film increases. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.201300439
  • 2013 • 196 Conformational disorder in alkylsiloxane monolayers at elevated temperatures
    Weber, J. and Balgar, T. and Hasselbrink, E.
    Journal of Chemical Physics 139 (2013)
    Vibrational sum frequency generation spectroscopy is used to characterize octadecylsiloxane monolayers on glass substrates at ambient conditions with a focus on thermally induced conformational disorder. Different modes of the C-H stretching vibrations of the terminal methyl groups and the methylene groups are therefore monitored in the frequency range of 2850-3000 cm-1. We observe a progressive increase of conformational disorder of the alkyl chains due to gauche defects over the temperature range from 300 to 510 K. The conformational disorder is reversible over a temperature range from 300 to about 410 K. But after heating to temperatures above 410 K, order is not reestablished on the time scale of the experiment. These results suggest that the assumption of an all-trans configuration of the alkyl chains is an over-simplification which increasingly misrepresents the situation for elevated temperatures which are still well below the one at which decomposition starts. © 2013 AIP Publishing LLC.
    view abstractdoi: 10.1063/1.4846298
  • 2013 • 195 Slippery liquid-infused porous surfaces showing marine antibiofouling properties
    Xiao, L. and Li, J. and Mieszkin, S. and Di Fino, A. and Clare, A.S. and Callow, M.E. and Callow, J.A. and Grunze, M. and Rosenhahn, A. and Levkin, P.A.
    ACS Applied Materials and Interfaces 5 10074-10080 (2013)
    Marine biofouling is a longstanding problem because of the constant challenges placed by various fouling species and increasingly restricted environmental regulations for antifouling coatings. Novel nonbiocidal strategies to control biofouling will necessitate a multifunctional approach to coating design. Here we show that slippery liquid-infused porous surfaces (SLIPSs) provide another possible strategy to obtaining promising antifouling coatings. Microporous butyl methacrylate-ethylene dimethacrylate (BMA-EDMA) surfaces are prepared via UV-initiated free-radical polymerization. Subsequent infusion of fluorocarbon lubricants (Krytox103, Krytox100, and Fluorinert FC-70) into the porous microtexture results in liquid-repellent slippery surfaces. To study the interaction with marine fouling organisms, settlement of zoospores of the alga Ulva linza and cypris larvae of the barnacle Balanus amphitrite is tested in laboratory assays. BMA-EDMA surfaces infused with Krytox103 and Krytox100 exhibit remarkable inhibition of settlement (attachment) of both spores and cyprids to a level comparable to that of a poly(ethylene glycol) (PEG)-terminated self-assembled monolayer. In addition, the adhesion strength of sporelings (young plants) of U. linza is reduced for BMA-EDMA surfaces infused with Krytox103 and Krytox100 compared to pristine (noninfused) BMA-EDMA and BMA-EDMA infused with Fluorinert FC-70. Immersion tests suggest a correlation between the stability of slippery coatings in artificial seawater and fouling resistance efficacy. The results indicate great potential for the application of this concept in fouling-resistant marine coatings. © 2013 American Chemical Society.
    view abstractdoi: 10.1021/am402635p
  • 2013 • 194 Hot embossed microtopographic gradients reveal morphological cues that guide the settlement of zoospores
    Xiao, L. and Thompson, S.E.M. and Röhrig, M. and Callow, M.E. and Callow, J.A. and Grunze, M. and Rosenhahn, A.
    Langmuir 29 1093-1099 (2013)
    Among different surface cues, the settlement of cells and larvae of marine macrofouling organisms has been found to be strongly influenced by surface microtopographies. In this article, the settlement of zoospores of the green alga Ulva linza on a surface topographic gradient has been investigated. "Honeycomb" gradient structures with feature sizes ranging from 1 to 10 μm were prepared by hot embossing, and the effect on the density of spores that attached in settlement assays was quantified. The highest density of spores was found when the size of the microstructures was similar to or larger than the size of the spores. With decreasing size of the structures, spore settlement density decreased. Interestingly, spore settlement density correlated with the Wenzel roughness of the surfaces. "Kink sites" on the surface played an important role and resembled preferred attachment positions. Furthermore, the gradients allowed the minimum pit size that the spores were able to squeeze into to be determined. © 2012 American Chemical Society.
    view abstractdoi: 10.1021/la303832u
  • 2013 • 193 Medical applications of surface-enhanced Raman scattering
    Xie, W. and Schlücker, S.
    Physical Chemistry Chemical Physics 15 5329-5344 (2013)
    This perspective article provides an overview of selected medical applications of surface-enhanced Raman scattering (SERS), highlighting recent developments and trends. The use of SERS for detection, analysis and imaging has attracted great interest in the past decade owing to its high sensitivity and molecular fingerprint specificity. SERS can deliver chemical and structural information from analytes rapidly and nondestructively in a label-free manner. Alternatively, SERS labels or nanotags, when conjugated to target-specific ligands, can be employed for the selective detection and localization of the corresponding target molecule. Biomedical applications based on both approaches are highlighted. © 2013 the Owner Societies.
    view abstractdoi: 10.1039/c3cp43858a
  • 2013 • 192 Cooperative dynamics of microtubule ensembles: Polymerization forces and rescue-induced oscillations
    Zelinski, B. and Kierfeld, J.
    Physical Review E - Statistical, Nonlinear, and Soft Matter Physics 87 (2013)
    We investigate the cooperative dynamics of an ensemble of N microtubules growing against an elastic barrier. Microtubules undergo so-called catastrophes, which are abrupt stochastic transitions from a growing to a shrinking state, and rescues, which are transitions back to the growing state. Microtubules can exert pushing or polymerization forces on an obstacle, such as an elastic barrier, if the growing end is in contact with the obstacle. We use dynamical mean-field theory and stochastic simulations to analyze a model where each microtubule undergoes catastrophes and rescues and where microtubules interact by force sharing. For zero rescue rate, cooperative growth terminates in a collective catastrophe. The maximal polymerization force before catastrophes grows linearly with N for small N or a stiff elastic barrier, in agreement with available experimental results, whereas it crosses over to a logarithmic dependence for larger N or a soft elastic barrier. For a nonzero rescue rate and a soft elastic barrier, the dynamics becomes oscillatory with both collective catastrophe and rescue events, which are part of a robust limit cycle. Both the average and maximal polymerization forces then grow linearly with N, and we investigate their dependence on tubulin on-rates and rescue rates, which can be involved in cellular regulation mechanisms. We further investigate the robustness of the collective catastrophe and rescue oscillations with respect to different catastrophe models. © 2013 American Physical Society.
    view abstractdoi: 10.1103/PhysRevE.87.012703
  • 2012 • 191 Self-cleaning functional molecular materials
    Avinash, M.B. and Verheggen, E. and Schmuck, C. and Govindaraju, T.
    Angewandte Chemie - International Edition 51 10324-10328 (2012)
    Clean and polish: The spontaneous hierarchical molecular assembly of a naphthalenediimide derivative is used to form microarrays by a simple solution-processing technique. This method is further employed to fabricate a self-cleaning surface with very low slide angle (3°) and contact angle hysteresis (1°). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201204608
  • 2012 • 190 Intestinal aspartate proteases TiCatD and TiCatD2 of the haematophagous bug Triatoma infestans (Reduviidae): Sequence characterisation, expression pattern and characterisation of proteolytic activity
    Balczun, C. and Siemanowski, J. and Pausch, J.K. and Helling, S. and Marcus, K. and Stephan, C. and Meyer, H.E. and Schneider, T. and Cizmowski, C. and Oldenburg, M. and Höhn, S. and Meiser, C.K. and Schuhmann, W. and Schaub, G.A.
    Insect Biochemistry and Molecular Biology 42 240-250 (2012)
    Two aspartate protease encoding complementary deoxyribonucleic acids (cDNA) were characterised from the small intestine (posterior midgut) of Triatoma infestans and the corresponding genes were named TiCatD and TiCatD2. The deduced 390 and 393 amino acid sequences of both enzymes contain two regions characteristic for cathepsin D proteases and the conserved catalytic aspartate residues forming the catalytic dyad, but only TiCatD2 possesses an entire C-terminal proline loop. The amino acid sequences of TiCatD and TiCatD2 show 51-58% similarity to other insect cathepsin D-like proteases and, respectively, 88 and 58% similarity to the aspartate protease ASP25 from T. infestans available in the GenBank database. In phylogenetic analysis, TiCatD and ASP25 clearly separate from cathepsin D-like sequences of other insects, TiCatD2 groups with cathepsin D-like proteases with proline loop. The activity of purified TiCatD and TiCatD2 was highest between pH 2 and 4, respectively, and hence, deviate from the pH values of the lumen of the small intestine, which varied in correlation with the time after feeding between pH 5.2 and 6.7 as determined by means of micro pH electrodes. Both cathepsins, TiCatD and TiCatD2, were purified from the lumen of the small intestine using pepstatin affinity chromatography and identified by nanoLC-ESI-MS/MS analysis as those encoded by the cDNAs. The proteolytic activity of the purified enzymes is highest at pH 3 and the respective genes are expressed in the both regions of the midgut, stomach (anterior midgut) and small intestine, not in the rectum, salivary glands, Malpighian tubules or haemocytes. The temporal expression pattern of both genes in the small intestine after feeding revealed a feeding dependent regulation for TiCatD but not for TiCatD2. © 2011 Elsevier Ltd.
    view abstractdoi: 10.1016/j.ibmb.2011.12.006
  • 2012 • 189 Robust workflow for iTRAQ-based peptide and protein quantification
    Beck, F. and Burkhart, J.M. and Geiger, J. and Zahedi, R.P. and Sickmann, A.
    Methods in Molecular Biology 893 101-113 (2012)
    Quantitative proteomics has become a routinely used technique to globally compare protein content and expression profiles of biological samples, for instance after differential stimulation. In this context, chemical stable isotope-based labeling techniques, such as ICAT and iTRAQ, have been successfully applied in a large variety of studies. Since iTRAQ labels are isobaric, quantitation is conducted on the MS/MS level. Consequently, up to eight samples can be multiplexed and quantified in a single experiment without increasing sample complexity. Here, we present a robust workflow to conduct iTRAQ quantification of biological samples such as human platelets, which comprises (a) an adequate sample preparation procedure, (b) an optimized tryptic digestion protocol, (c) SPE desalting and subsequent peptide labeling using a 4-plex iTRAQ labeling kit, and (d) fractionation of the obtained peptide mixture by strong cation exchange chromatography. © 2012 Springer Science+Business Media, LLC.
    view abstractdoi: 10.1007/978-1-61779-885-6_8
  • 2012 • 188 Artificial signal transduction with primary and secondary messengers
    Bernitzki, K. and Maue, M. and Schrader, T.
    Chemistry - A European Journal 18 13412-13417 (2012)
    The complete, entirely artificial, signal-transduction process was realized with a pair of tailored transmembrane units that were equipped with receptor- and reactive sites at both amphiphilic ends. Thus, docking of the primary messenger, transmission of the signal, and release of the secondary messenger could all be imitated in a single experimental setup. The system imitates the signaling principle of receptor tyrosine kinases and employs bisphosphonate head-groups for oligoamine-recognition and a pair of thiol nucleophiles and pyridine disulfide tail-groups for intravesicle SN2 displacement. This system operates in a unidirectional fashion, does not suffer from intervesicle competition, and is highly sensitive towards the lipid composition of the membrane and the nature of the primary messenger. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/chem.201200623
  • 2012 • 187 UV-photo graft functionalization of polyethersulfone membrane with strong polyelectrolyte hydrogel and its application for nanofiltration
    Bernstein, R. and Antón, E. and Ulbricht, M.
    ACS Applied Materials and Interfaces 4 3438-3446 (2012)
    A strong polyelectrolyte hydrogel was graft copolymerized on a polyethersulfone (PES) ultrafiltration (UF) membrane using vinyl sulfonic acid (VSA) as the functional monomer, and N,N′-methylenbisacrylamide (MBAA) as the cross-linker monomer. This was carried out in one simple step using the UV photoirradiation method. The effect of the polymerization conditions on the degree of grafting (DG) was investigated using the gravimetric method which measures the total hydrogel grafted on the membrane, and with ATR-FTIR spectroscopy which indicates the functional monomer fraction in the hydrogel layer. The VSA could not graft polymerize without the cross-linker as comonomer. An increase in the cross-linker fraction from 0.25 to 2.5 mol % (relative to the functional monomer VSA) resulted in a higher DG. Although the surface morphology changed upon modification, the resulting surface roughness as measured by AFM was very low. From the monitoring of DG with UV time (4.5-30 min) at constant conditions, it was deduced that during the early stages of the polymerization mainly the cross-linker was grafted, thus inducing the graft copolymerization of the functional monomer. Polymerization using a higher monomer concentration (12.5-40% VSA) at constant monomer/cross-linker ratio resulted in a higher VSA fraction in the grafted hydrogel, although the gravimetric DG was similar. Ion exchange capacity and X-ray photoelectron spectroscopy measured after modification under the different conditions supported these findings. The new membranes were tested under nanofiltration (NF) conditions. A NF membrane could be obtained when the MBAA fraction was above 0.25%. The Na 2SO 4 rejection was 90-99% and the permeability 10-1 L m -2 h -1 bar -1 when the MBAA fraction increased from 0.75 to 2.5%. The order of rejection of single salts solution was Na 2SO 4 &gt; MgSO 4 ≈ NaCl &gt; CaCl 2, as expected on the basis of Donnan exclusion for negatively charged NF membranes. An increase in the salts rejection with increasing degree of cross-linking and VSA fraction was attributed to an increase in the membrane charge density and to steric exclusion that also resulted in an increase of rejection for uncharged solutes such as sucrose or glucose. The new membrane presented a high, essentially unchanged Na 2SO 4 rejection (&gt;97%) in the range of salt concentrations up to 4 g/L, and only slightly reduced rejection (&gt;92%) at a concentration of 8 g/L; this can be related to its high barrier layer charge density measured by ion exchange capacity. In addition, because poly(vinyl sulfonic acid) (PVSA) is a strong polyelectrolyte the membrane separation performance was stable in the range of pH 1.5 to pH 10. © 2012 American Chemical Society.
    view abstractdoi: 10.1021/am300426c
  • 2012 • 186 Electron transport at surfaces and interfaces
    Bobisch, C.A. and Möller, R.
    Chimia 66 23-30 (2012)
    Here we present two techniques which give insight on transport phenomena with atomic resolution. Ballistic electron emission microscopy is used to study the ballistic transport through layered heterogeneous systems. The measured ballistic fraction of the tunneling current provides information about lossless transport channels through metallic layers and organic adsorbates. The transport characteristics of Bi(111)/Si Schottky devices and the influence of the organic adsorbates perylene tetracaboxylic dianhydride acid and C 60 on the ballistic current are discussed. Scanning tunneling potentiometry gives access to the lateral transport along a surface, thus scattering processes within two-dimensional electron systems for the Bi(111) surface and the Si(111)(√3×√3)-Ag surface could be visualized. © Schweizerische Chemische Gesellschaft.
    view abstractdoi: 10.2533/chimia.2012.23
  • 2012 • 185 Preparation of 24 ternary thin film materials libraries on a single substrate in one experiment for irreversible high-throughput studies
    Buenconsejo, P.J.S. and Siegel, A. and Savan, A. and Thienhaus, S. and Ludwig, Al.
    ACS Combinatorial Science 14 25-30 (2012)
    For different areas of combinatorial materials science, it is desirable to have multiple materials libraries: especially for irreversible high-throughput studies, like, for example, corrosion resistance testing in different media or annealing of complete materials libraries at different temperatures. Therefore a new combinatorial sputter-deposition process was developed which yields 24 materials libraries in one experiment on a single substrate. It is discussed with the example of 24 Ti-Ni-Ag materials libraries. They are divided based on the composition coverage and orientation of composition gradient into two sets of 12 nearly identical materials libraries. Each materials library covers at least 30-40% of the complete ternary composition range. An acid etch test in buffered-HF solution was performed, illustrating the feasibility of our approach for destructive materials characterization. The results revealed that within the composition range of Ni < 30 at.%, the films were severely etched. The composition range which shows reversible martensitic transformations was confirmed to be outside this region. The high output of the present method makes it attractive for combinatorial studies requiring multiple materials libraries. © 2011 American Chemical Society.
    view abstractdoi: 10.1021/co2001263
  • 2012 • 184 Optimizing the deposition of hydrogen evolution sites on suspended semiconductor particles using on-line photocatalytic reforming of aqueous methanol solutions
    Busser, G.W. and Mei, B. and Muhler, M.
    ChemSusChem 5 2200-2206 (2012)
    The deposition of hydrogen evolution sites on photocatalysts is a crucial step in the multistep process of synthesizing a catalyst that is active for overall photocatalytic water splitting. An alternative approach to conventional photodeposition was developed, applying the photocatalytic reforming of aqueous methanol solutions to deposit metal particles on semiconductor materials such as Ga2O3 and (Ga0.6Zn0.4)(N 0.6O0.4). The method allows optimizing the loading of the co-catalysts based on the stepwise addition of their precursors and the continuous online monitoring of the evolved hydrogen. Moreover, a synergetic effect between different co-catalysts can be directly established. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.201200374
  • 2012 • 183 The energy barrier in singlet fission can be overcome through coherent coupling and entropic gain
    Chan, W.-L. and Ligges, M. and Zhu, X.-Y.
    Nature Chemistry 4 840-845 (2012)
    One strategy to improve solar-cell efficiency is to generate two excited electrons from just one photon through singlet fission, which is the conversion of a singlet (S 1) into two triplet (T 1) excitons. For efficient singlet fission it is believed that the cumulative energy of the triplet states should be no more than that of S 1. However, molecular analogues that satisfy this energetic requirement do not show appreciable singlet fission, whereas crystalline tetracene displays endothermic singlet fission with near-unity quantum yield. Here we probe singlet fission in tetracene by directly following the intermediate multiexciton (ME) state. The ME state is isoenergetic with 2×T 1, but fission is not activated thermally. Rather, an S 1 ⇔ ME superposition formed through a quantum-coherent process allows access to the higher-energy ME. We attribute entropic gain in crystalline tetracene as the driving force for the subsequent decay of S 1 ⇔ ME into 2×T 1, which leads to a high singlet-fission yield. © 2012 Macmillan Publishers Limited. All rights reserved.
    view abstractdoi: 10.1038/nchem.1436
  • 2012 • 182 Microstructural impact of anodic coatings on the electrochemical chlorine evolution reaction
    Chen, R. and Trieu, V. and Zeradjanin, A.R. and Natter, H. and Teschner, D. and Kintrup, J. and Bulan, A. and Schuhmann, W. and Hempelmann, R.
    Physical Chemistry Chemical Physics 14 7392-7399 (2012)
    Sol-gel Ru 0.3Sn 0.7O 2 electrode coatings with crack-free and mud-crack surface morphology deposited onto a Ti-substrate are prepared for a comparative investigation of the microstructural effect on the electrochemical activity for Cl 2 production and the Cl 2 bubble evolution behaviour. For comparison, a state-of-the-art mud-crack commercial Ru 0.3Ti 0.7O 2 coating is used. The compact coating is potentially durable over a long term compared to the mud-crack coating due to the reduced penetration of the electrolyte. Ti L-edge X-ray absorption spectroscopy confirms that a TiO x interlayer is formed between the mud-crack Ru 0.3Sn 0.7O 2 coating and the underlying Ti-substrate due to the attack of the electrolyte. Meanwhile, the compact coating shows enhanced activity in comparison to the commercial coating, benefiting from the nanoparticle-nanoporosity architecture. The dependence of the overall electrode polarization behaviour on the local activity and the bubble evolution behaviour for the Ru 0.3Sn 0.7O 2 coatings with different surface microstructure are evaluated by means of scanning electrochemical microscopy and microscopic bubble imaging. © 2012 the Owner Societies.
    view abstractdoi: 10.1039/c2cp41163f
  • 2012 • 181 A facile route to reassemble titania nanoparticles into ordered chain-like networks on substrate
    Cheng, Y.-J. and Wolkenhauer, M. and Bumbu, G.-G. and Gutmann, J.S.
    Macromolecular Rapid Communications 33 218-224 (2012)
    A facile route to reassemble titania nanoparticles within the titania-block copolymer composite films has been developed. The titania nanoparticles templated by the amphiphilic block copolymer of poly(styrene)-block-poly (ethylene oxide) (PS-b-PEO) were frozen in the continuous PS matrix. Upon UV exposure, the PS matrix was partially degraded, allowing the titania nanoparticles to rearrange into chain-like networks exhibiting a closer packing. The local structures of the Titania chain-like networks were investigated by both AFM and SEM; the lateral structures and vertical structures of the films were studied by GISAXS and X-ray reflectivity respectively. Both the image analysis and X-ray scattering characterization prove the reassembly of the titania nanoparticles after UV exposure. The mechanism of the nanoparticle assembly is discussed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/marc.201100638
  • 2012 • 180 Microwave-hydrothermal synthesis and characterization of nanostructured copper substituted ZnM2O4 (M = Al, Ga) spinels as precursors for thermally stable Cu catalysts
    Conrad, F. and Massue, C. and Kühl, S. and Kunkes, E. and Girgsdies, F. and Kasatkin, I. and Zhang, B. and Friedrich, M. and Luo, Y. and Armbrüster, M. and Patzke, G.R. and Behrens, M.
    Nanoscale 4 2018-2028 (2012)
    Nanostructured Cu<inf>x</inf>Zn<inf>1-x</inf>Al<inf>2</inf>O<inf>4</inf> with a Cu:Zn ratio of: has been prepared by a microwave-assisted hydrothermal synthesis at 150°C and used as a precursor for Cu/ZnO/Al<inf>2</inf>O <inf>3</inf>-based catalysts. The spinel nanoparticles exhibit an average size of approximately 5 nm and a high specific surface area (above 250 m2 g-1). Cu nanoparticles of an average size of 3.3 nm can be formed by reduction of the spinel precursor in hydrogen and the accessible metallic Cu(0) surface area of the reduced catalyst was 8 m2 g-1. The catalytic performance of the material in CO<inf>2</inf> hydrogenation and methanol steam reforming was compared with conventionally prepared Cu/ZnO/Al<inf>2</inf>O<inf>3</inf> reference catalysts. The observed lower performance of the spinel-based samples is attributed to a lack of synergetic interaction of the Cu nanoparticles with ZnO due to the incorporation of Zn 2+ in the stable spinel lattice. Despite its lower performance, however, the nanostructured nature of the spinel catalyst was stable after thermal treatment up to 500°C in contrast to other Cu-based catalysts. Furthermore, a large fraction of the re-oxidized copper migrates back into the spinel upon calcination of the reduced catalyst, thereby enabling a regeneration of sintered catalysts after prolonged usage at high temperatures. Similarly prepared samples with Ga instead of Al exhibit a more crystalline catalyst with a spinel particle size around 20 nm. The slightly decreased Cu(0) surface area of 3.2 m2 g-1 due to less copper incorporation is not a significant drawback for the methanol steam reforming. © The Royal Society of Chemistry 2012.
    view abstractdoi: 10.1039/c2nr11804a
  • 2012 • 179 Understanding properties of electrified interfaces as a prerequisite for label-free DNA hybridization detection
    Gebala, M. and Schuhmann, W.
    Physical Chemistry Chemical Physics 14 14933-14942 (2012)
    Label-free electrochemical detection of DNA hybridization with high selectivity and sensitivity is only achievable if the properties of DNA at an electrified interface are understood in depth. After a short summary of concepts of electrochemical DNA detection as well as initial attempts towards label-free DNA assays the review discusses the physico-chemical properties and differences between single-stranded and double-stranded DNA immobilized at electrode surfaces in the light of their persistence lengths, structural conformation, impact of the charge screening by ion condensation and the electric field generated upon polarization of the electrode. Electrochemical impedance spectroscopy as a tool for label-free elucidation of DNA hybridization is reviewed and the necessity for an in-depth understanding of the interfacial properties is highlighted. Our major aim is to demonstrate the advantageous application of specifically designed intercalating compounds for the design of label-free detection of DNA hybridization. This journal is © 2012 the Owner Societies.
    view abstractdoi: 10.1039/c2cp42382k
  • 2012 • 178 Impact of the nanoparticle-protein corona on colloidal stability and protein structure
    Gebauer, J.S. and Malissek, M. and Simon, S. and Knauer, S.K. and Maskos, M. and Stauber, R.H. and Peukert, W. and Treuel, L.
    Langmuir 28 9673-9679 (2012)
    In biological fluids, proteins may associate with nanoparticles (NPs), leading to the formation of a so-called "protein corona" largely defining the biological identity of the particle. Here, we present a novel approach to assess apparent binding affinities for the adsorption/desorption of proteins to silver NPs based on the impact of the corona formation on the agglomeration kinetics of the colloid. Affinities derived from circular dichroism measurements complement these results, simultaneously elucidating structural changes in the adsorbed protein. Employing human serum albumin as a model, apparent affinities in the nanomolar regime resulted from both approaches. Collectively, our findings now allow discrimination between the formation of protein mono- and multilayers on NP surfaces. © 2012 American Chemical Society.
    view abstractdoi: 10.1021/la301104a
  • 2012 • 177 Fluorophore labeled kinase detects ligands that bind within the MAPK insert of p38α kinase
    Getlik, M. and Simard, J.R. and Termathe, M. and Grütter, C. and Rabiller, M. and van Otterlo, W.A.L. and Rauh, D.
    PLoS ONE 7 (2012)
    The vast majority of small molecules known to modulate kinase activity, target the highly conserved ATP-pocket. Consequently, such ligands are often less specific and in case of inhibitors, this leads to the inhibition of multiple kinases. Thus, selective modulation of kinase function remains a major hurdle. One of the next great challenges in kinase research is the identification of ligands which bind to less conserved sites and target the non-catalytic functions of protein kinases. However, approaches that allow for the unambiguous identification of molecules that bind to these less conserved sites are few in number. We have previously reported the use of fluorescent labels in kinases (FLiK) to develop direct kinase binding assays that exclusively detect ligands which stabilize inactive (DFG-out) kinase conformations. Here, we present the successful application of the FLiK approach to develop a high-throughput binding assay capable of directly monitoring ligand binding to a remote site within the MAPK insert of p38α mitogen-activated protein kinase (MAPK). Guided by the crystal structure of an initially identified hit molecule in complex with p38α, we developed a tight binding ligand which may serve as an ideal starting point for further investigations of the biological function of the MAPK insert in regulating the p38α signaling pathway. © 2012 Getlik et al.
    view abstractdoi: 10.1371/journal.pone.0039713
  • 2012 • 176 Precise hierarchical self-assembly of multicompartment micelles
    Gröschel, A.H. and Schacher, F.H. and Schmalz, H. and Borisov, O.V. and Zhulina, E.B. and Walther, A. and Müller, A.H.E.
    Nature Communications 3 (2012)
    Hierarchical self-assembly offers elegant and energy-efficient bottom-up strategies for the structuring of complex materials. For block copolymers, the last decade witnessed great progress in diversifying the structural complexity of solution-based assemblies into multicompartment micelles. However, a general understanding of what governs multicompartment micelle morphologies and polydispersity, and how to manipulate their hierarchical superstructures using straightforward concepts and readily accessible polymers remains unreached. Here we demonstrate how to create homogeneous multicompartment micelles with unprecedented structural control via the intermediate pre-assembly of subunits. This directed self-assembly leads to a step-wise reduction of the degree of conformational freedom and dynamics and avoids undesirable kinetic obstacles during the structure build-up. It yields a general concept for homogeneous populations of well-defined multicompartment micelles with precisely tunable patchiness, while using simple linear ABC triblock terpolymers. We further demonstrate control over the hierarchical step-growth polymerization of multicompartment micelles into micron-scale segmented supracolloidal polymers as an example of programmable mesoscale colloidal hierarchies via well-defined patchy nanoobjects. © 2012 Macmillan Publishers Limited. All rights reserved.
    view abstractdoi: 10.1038/ncomms1707
  • 2012 • 175 Decay kinetics of cluster-beam-deposited metal particles
    Grönhagen, N. and Järvi, T.T. and Miroslawski, N. and Hövel, H. and Moseler, M.
    Journal of Physical Chemistry C 116 19327-19334 (2012)
    High-precision experiments and atomistic simulations are used to determine the flattening kinetics of mass-selected 55-147 atom Ag clusters deposited on Au(111). The clusters are shown to align epitaxially and decay through an exchange pathway with a range of rate-limiting barriers, from ca. 0.25 to 0.4 eV, depending on the shape of the particle. It is also shown that nonlocal effects at the Au-Ag interface lead to a dramatic reduction in the barrier of the dominant transition pathway, requiring ab initio methods for correct modeling. As a result, quantitative correspondence between experimental and simulated island heights is obtained. © 2012 American Chemical Society.
    view abstractdoi: 10.1021/jp305089d
  • 2012 • 174 Direct determination of minority carrier diffusion lengths at axial GaAs nanowire p-n junctions
    Gutsche, C. and Niepelt, R. and Gnauck, M. and Lysov, A. and Prost, W. and Ronning, C. and Tegude, F.-J.
    Nano Letters 12 1453-1458 (2012)
    Axial GaAs nanowire p-n diodes, possibly one of the core elements of future nanowire solar cells and light emitters, were grown via the Au-assisted vapor-liquid-solid mode, contacted by electron beam lithography, and investigated using electron beam induced current measurements. The minority carrier diffusion lengths and dynamics of both, electrons and holes, were determined directly at the vicinity of the p-n junction. The generated photocurrent shows an exponential decay on both sides of the junction and the extracted diffusion lengths are about 1 order of magnitude lower compared to bulk material due to surface recombination. Moreover, the observed strong diameter-dependence is well in line with the surface-to-volume ratio of semiconductor nanowires. Estimating the surface recombination velocities clearly indicates a nonabrupt p-n junction, which is in essential agreement with the model of delayed dopant incorporation in the Au-assisted vapor-liquid-solid mechanism. Surface passivation using ammonium sulfide effectively reduces the surface recombination and thus leads to higher minority carrier diffusion lengths. © 2012 American Chemical Society.
    view abstractdoi: 10.1021/nl204126n
  • 2012 • 173 Subsurface influence on the structure of protein adsorbates as revealed by in situ X-ray reflectivity
    Hähl, H. and Evers, F. and Grandthyll, S. and Paulus, M. and Sternemann, C. and Loskill, P. and Lessel, M. and Hüsecken, A.K. and Brenner, T. and Tolan, M. and Jacobs, K.
    Langmuir 28 7747-7756 (2012)
    The adsorption process of proteins to surfaces is governed by the mutual interactions among proteins, the solution, and the substrate. Interactions arising from the substrate are usually attributed to the uppermost atomic layer. This actual surface defines the surface chemistry and hence steric and electrostatic interactions. For a comprehensive understanding, however, the interactions arising from the bulk material also have to be considered. Our protein adsorption experiments with globular proteins (α-amylase, bovine serum albumin, and lysozyme) clearly reveal the influence of the subsurface material via van der Waals forces. Here, a set of functionalized silicon wafers enables a distinction between the effects of surface chemistry and the subsurface composition of the substrate. Whereas the surface chemistry controls whether the individual proteins are denatured, the strength of the van der Waals forces affects the final layer density and hence the adsorbed amount of proteins. The results imply that van der Waals forces mainly influence surface processes, which govern the structure formation of the protein adsorbates, such as surface diffusion and spreading. © 2012 American Chemical Society.
    view abstractdoi: 10.1021/la300850g
  • 2012 • 172 The biocompatibility of metal-organic framework coatings: An investigation on the stability of SURMOFs with regard to water and selected cell culture media
    Hanke, M. and Arslan, H.K. and Bauer, S. and Zybaylo, O. and Christophis, C. and Gliemann, H. and Rosenhahn, A. and Wöll, C.
    Langmuir 28 6877-6884 (2012)
    Highly porous thin films based on a [Cu(bdc) 2] n (bdc = benzene-1,4-dicarboxylic acid) metal-organic framework, MOF, grown using liquid-phase epitaxy (LPE) show remarkable stability in pure water as well as in artificial seawater. This opens the possibility to use these highly porous coatings for environmental and life science applications. Here we characterize in detail the stability of these SURMOF 2 thin films under aqueous and cell culture conditions. We find that the material degrades only very slowly in water and artificial seawater (ASW) whereas in typical cell culture media (PBS and DMEM) a rapid dissolution is observed. The release of Cu 2+ ions resulting from the dissolution of the SURMOF 2 in the liquids exhibits no adverse effect on the adhesion of fibroblasts, prototype eukaryotic cells, to the substrate and their subsequent proliferation, thus demonstrating the biocompatibility of SURMOF 2 surface coatings. Thus, the results are an important step toward application of these porous materials as a slow release matrix, for example, for pharmaceuticals and growth factors. © 2012 American Chemical Society.
    view abstractdoi: 10.1021/la300457z
  • 2012 • 171 Interplay of wrinkles, strain, and lattice parameter in graphene on iridium
    Hattab, H. and N'Diaye, A.T. and Wall, D. and Klein, C. and Jnawali, G. and Coraux, J. and Busse, C. and Van Gastel, R. and Poelsema, B. and Michely, T. and Meyer zu Heringdorf, F.-J. and Horn-Von Hoegen, M.
    Nano Letters 12 678-682 (2012)
    Following graphene growth by thermal decomposition of ethylene on Ir(111) at high temperatures we analyzed the strain state and the wrinkle formation kinetics as function of temperature. Using the moiré spot separation in a low energy electron diffraction pattern as a magnifying mechanism for the difference in the lattice parameters between Ir and graphene, we achieved an unrivaled relative precision of ±0.1 pm for the graphene lattice parameter. Our data reveals a characteristic hysteresis of the graphene lattice parameter that is explained by the interplay of reversible wrinkle formation and film strain. We show that graphene on Ir(111) always exhibits residual compressive strain at room temperature. Our results provide important guidelines for strategies to avoid wrinkling. © 2011 American Chemical Society.
    view abstractdoi: 10.1021/nl203530t
  • 2012 • 170 Characterizing permeability and stability of microcapsules for controlled drug delivery by dynamic NMR microscopy
    Henning, S. and Edelhoff, D. and Ernst, B. and Leick, S. and Rehage, H. and Suter, D.
    Journal of Magnetic Resonance 221 11-18 (2012)
    Microscopic capsules made from polysaccharides are used as carriers for drugs and food additives. Here, we use NMR microscopy to assess the permeability of capsule membranes and their stability under different environmental conditions. The results allow us to determine the suitability of different capsules for controlled drug delivery. As a measure of the membrane permeability, we monitor the diffusion of paramagnetic molecules into the microcapsules by dynamic NMR microimaging. We obtained the diffusion coefficients of the probe molecules in the membranes and in the capsule core by comparing the measured time dependent concentration maps with numerical solutions of the diffusion equation. The results reveal that external coatings strongly decrease the permeability of the capsules. In addition, we also visualized that the capsules are stable under gastric conditions but dissolve under simulated colonic conditions, as required for targeted drug delivery. Depending on the capsule, the timescales for these processes range from 1 to 28 h. © 2012 Elsevier Inc. All rights reserved.
    view abstractdoi: 10.1016/j.jmr.2012.05.009
  • 2012 • 169 Stress-induced melting of crystals in natural rubber: A new way to tailor the transition temperature of shape memory polymers
    Heuwers, B. and Quitmann, D. and Katzenberg, F. and Tiller, J.C.
    Macromolecular Rapid Communications 33 1517-1522 (2012)
    Lightly cross-linked natural rubber (NR, cis-1,4-polyisoprene) was found to be an exceptional cold programmable shape memory polymer (SMP) with strain storage of up to 1000%. These networks are stabilized by strain-induced crystals. Here, we explore the influence of mechanical stress applied perpendicular to the elongation direction of the network on the stability of these crystals. We found that the material recovers its original shape at a critical transverse stress. It could be shown that this is due to a disruption of the strain-stabilizing crystals, which represents a completely new trigger for SMPs. The variation of transverse stress allows tuning of the trigger temperature Ttrig(σ) in a range of 45 to 0 °C, which is the first example of manipulating the transition of a crystal-stabilized SMP after programming. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/marc.201200313
  • 2012 • 168 Impact of single basepair mismatches on electron-transfer processes at Fc-PNA·DNA modified gold surfaces
    Hüsken, N. and Gȩbala, M. and Battistel, A. and La Mantia, F. and Schuhmann, W. and Metzler-Nolte, N.
    ChemPhysChem 13 131-139 (2012)
    Gold-surface grafted peptide nucleic acid (PNA) strands, which carry a redox-active ferrocene tag, present unique tools to electrochemically investigate their mechanical bending elasticity based on the kinetics of electron-transfer (ET) processes. A comparative study of the mechanical bending properties and the thermodynamic stability of a series of 12-mer Fc-PNA·DNA duplexes was carried out. A single basepair mismatch was integrated at all possible strand positions to provide nanoscopic insights into the physicochemical changes provoked by the presence of a single basepair mismatch with regard to its position within the strand. The ET processes at single mismatch Fc-PNA·DNA modified surfaces were found to proceed with increasing diffusion limitation and decreasing standard ET rate constants k 0 when the single basepair mismatch was dislocated along the strand towards its free-dangling Fc-modified end. The observed ET characteristics are considered to be due to a punctual increase in the strand elasticity at the mismatch position. The kinetic mismatch discrimination with respect to the fully-complementary duplex presents a basis for an electrochemical DNA sensing strategy based on the Fc-PNA·DNA bending dynamics for loosely packed monolayers. In a general sense, the strand elasticity presents a further physicochemical property which is affected by a single basepair mismatch which may possibly be used as a basis for future DNA sensing concepts for the specific detection of single basepair mismatches. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cphc.201100578
  • 2012 • 167 Bioconjugated silicon quantum dots from one-step green synthesis
    Intartaglia, R. and Barchanski, A. and Bagga, K. and Genovese, A. and Das, G. and Wagener, P. and Di Fabrizio, E. and Diaspro, A. and Brandi, F. and Barcikowski, S.
    Nanoscale 4 1271-1274 (2012)
    Biofunctionalized silicon quantum dots were prepared through a one step strategy avoiding the use of chemical precursors. UV-Vis spectroscopy, Raman spectroscopy and HAADF-STEM prove oligonucleotide conjugation to the surface of silicon nanoparticle with an average size of 4 nm. The nanoparticle size results from the size-quenching effect during in situ conjugation. Photoemissive properties, conjugation efficiency and stability of these pure colloids were studied and demonstrate the bio-application potential, e.g. for nucleic acid vector delivery with semiconducting, biocompatible nanoparticles. © 2012 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c2nr11763k
  • 2012 • 166 Glucose oxidase/horseradish peroxidase Co-immobilized at a CNT-modified graphite electrode: Towards potentially implantable biocathodes
    Jia, W. and Jin, C. and Xia, W. and Muhler, M. and Schuhmann, W. and Stoica, L.
    Chemistry - A European Journal 18 2783-2786 (2012)
    Concerted efforts: A high-potential biocathode based on co-immobilization of glucose oxidase (GOx) and horseradish peroxidase (HRP) onto a carbon nanotube/carbon microfiber modified graphite rod electrode (CNT/CMF/GR) is described (see figure). The GOx/HRP biocathode shows a remarkable biocatalytic activity in the presence of glucose and oxygen. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/chem.201102921
  • 2012 • 165 Current induced surface diffusion on a single-crystalline silver nanowire
    Kaspers, M.R. and Bernhart, A.M. and Bobisch, C.A. and Möller, R.
    Nanotechnology 23 (2012)
    Scanning tunnelling microscopy was used to study the morphological changes of the surface of a single-crystalline silver nanowire caused by a lateral electron current. At current densities of about 1.5×10 7 A cm -2, surface atoms are extracted from step edges, resulting in the motion of surface steps, islands and holes with a thickness or depth of one monolayer. Upon current reversal the direction of the material transport can be altered. The findings are interpreted in terms of the wind force. © 2012 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0957-4484/23/20/205706
  • 2012 • 164 Sensitivity of the mott-schottky analysis in organic solar cells
    Kirchartz, T. and Gong, W. and Hawks, S.A. and Agostinelli, T. and MacKenzie, R.C.I. and Yang, Y. and Nelson, J.
    Journal of Physical Chemistry C 116 7672-7680 (2012)
    The application of Mott-Schottky analysis to capacitance-voltage measurements of polymer:fullerene solar cells is a frequently used method to determine doping densities and built-in voltages, which have important implications for understanding the device physics of these cells. Here we compare drift-diffusion simulations with experiments to explore the influence and the detection limit of doping in situations where device thickness and doping density are too low for the depletion approximation to be valid. The results of our simulations suggest that the typically measured values on the order of 5 × 10 16 cm -3 for doping density in thin films of 100 nm or lower may not be reliably determined from capacitance measurements and could originate from a completely intrinsic active layer. In addition, we explain how the violation of the depletion approximation leads to a strong underestimation of the actual built-in voltage by the built-in voltage V MS determined by Mott-Schottky analysis. © 2012 American Chemical Society.
    view abstractdoi: 10.1021/jp300397f
  • 2012 • 163 Interactions of multicationic bis(guanidiniocarbonylpyrrole) receptors with double-stranded nucleic acids: Syntheses, binding studies, and atomic force microscopy imaging
    Klemm, K. and Stojković, M.R. and Horvat, G. and Tomišić, V. and Piantanida, I. and Schmuck, C.
    Chemistry - A European Journal 18 1352-1363 (2012)
    Compounds 1-3, composed of two guanidiniocarbonylpyrrole moieties linked by oligoamide bridges and differing in number and type of basic groups, were prepared. The sites and degree of protonation of 1-3 depend strongly on the pH value. The interactions of these compounds with several double-stranded (ds) DNA and dsRNA were investigated by means of UV/Vis and CD spectroscopy as well as isothermal titration microcalorimetry (ITC). These studies revealed that the binding of 1-3 to the polynucleotides is driven by three factors, the presence of aliphatic amino groups, the protonation state of the compounds, and the steric properties of the polynucleotide binding site, that is, the shape and structure of their grooves. The results obtained by all applied methods consistently indicated that receptors 1-3 bind to the minor groove of DNA, but, by contrast, to the major groove of RNA. Additionally, it was shown by atomic force microscopy (AFM) imaging that upon interaction of compound 2 with calf thymus (ct) DNA induced aggregation of the DNA occurs, leading to pronounced changes in its secondary structure. © 2012 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/chem.201101544
  • 2012 • 162 Dynamic spin polarization by orientation-dependent separation in a ferromagnet-semiconductor hybrid
    Korenev, V.L. and Akimov, I.A. and Zaitsev, S.V. and Sapega, V.F. and Langer, L. and Yakovlev, D.R. and Danilov, Y.A. and Bayer, M.
    Nature Communications 3 (2012)
    Integration of magnetism into semiconductor electronics would facilitate an all-in-one-chip computer. Ferromagnet/bulk semiconductor hybrids have been, so far, mainly considered as key devices to read out the ferromagnetism by means of spin injection. Here we demonstrate that a Mn-based ferromagnetic layer acts as an orientation-dependent separator for carrier spins confined in a semiconductor quantum well that is set apart from the ferromagnet by a barrier only a few nanometers thick. By this spin-separation effect, a non-equilibrium electron-spin polarization is accumulated in the quantum well due to spin-dependent electron transfer to the ferromagnet. The significant advance of this hybrid design is that the excellent optical properties of the quantum well are maintained. This opens up the possibility of optical readout of the ferromagnet's magnetization and control of the non-equilibrium spin polarization in non-magnetic quantum wells. © 2012 Macmillan Publishers Limited. All rights reserved.
    view abstractdoi: 10.1038/ncomms1957
  • 2012 • 161 Catalytic role of gold nanoparticle in GaAs nanowire growth: A density functional theory study
    Kratzer, P. and Sakong, S. and Pankoke, V.
    Nano Letters 12 943-948 (2012)
    The energetics of Ga, As, and GaAs species on the Au(111) surface (employed as a model for Au nanoparticles) is investigated by means of density functional calculations. Apart from formation of the compound Au 7Ga 2, Ga is found to form a surface alloy with gold with comparable ΔH ∼ -0.5 eV for both processes. Dissociative adsorption of As 2 is found to be exothermic by more than 2 eV on both clean Au(111) and AuGa surface alloys. The As-Ga species formed by reaction of As with the surface alloy is sufficiently stable to cover the surface of an Au particle in vacuo in contact with a GaAs substrate. The results of the calculations are interpreted in the context of Au-catalyzed growth of GaAs nanowires. We argue that arsenic is supplied to the growth zone of the nanowire mainly by impingement of molecules on the gold particle and identify a regime of temperatures and As 2 partial pressures suitable for Au-catalyzed nanowire growth in molecular beam epitaxy. © 2012 American Chemical Society.
    view abstractdoi: 10.1021/nl204004p
  • 2012 • 160 Well-defined amphiphilic poly(2-oxazoline) ABA-triblock copolymers and their aggregation behavior in aqueous solution
    Krumm, C. and Fik, C.P. and Meuris, M. and Dropalla, G.J. and Geltenpoth, H. and Sickmann, A. and Tiller, J.C.
    Macromolecular Rapid Communications 33 1677-1682 (2012)
    Self-organization of block copolymers in solution is a way to obtain advanced functional superstructures. The synthesis of well-defined polymethyloxazoline-block-polyphenyloxazoline-block-polymethyloxazoline triblock copolymers is described and proven by 1H NMR spectroscopy, SEC, and ESI-MS. The surprisingly water- soluble block copolymers do self-organize in aqueous solutions uniquely forming three coexisting well-defined structures: unimolecular micelles, micellar aggregates, and very form-stable polymersomes. This is the first example of a polymersome forming ABA-triblock copolymer with a glassy middle block. The spherical vesicles are analysed by scanning electron microscopy and transmission electron microscopy. It could be shown that these vesicles are indeed hollow spheres. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/marc.201200192
  • 2012 • 159 Synthesis and mechanical properties of organic-inorganic hybrid materials from lignin and polysiloxanes
    Lippach, A.K.W. and Krämer, R. and Hansen, M.R. and Roos, S. and Stöwe, K. and Stommel, M. and Wenz, G. and Maier, W.F.
    ChemSusChem 5 1778-1786 (2012)
    The preparation of silica-containing organic-inorganic hybrid materials composed of kraft lignin, alkoxysilanes, and organic linkers was investigated. 3-Glycidyloxypropyltrimethoxysilane, 3-(triethoxysilyl)propylisocyanate (IPTES), and bis(trimethoxysilyl)hexane were selected as the most promising linkers. The best materials obtained showed improved mechanical and thermal properties compared with lignin itself. The reaction of the hydroxyl groups with IPTES and the sol-gel reaction between the organic linker molecules were studied by attenuated total reflectance FTIR and solid-state 29Si magic-angle spinning NMR spectroscopy. The homogeneous composition was demonstrated by electron microscopy and energy-dispersive X-ray spectroscopy mapping. The mechanical properties were investigated by microindentation and dynamic mechanical thermal analysis. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.201200095
  • 2012 • 158 E. coli LoiP (YggG), a metalloprotease hydrolyzing Phe-Phe bonds
    Lütticke, C. and Hauske, P. and Lewandrowski, U. and Sickmann, A. and Kaiser, M. and Ehrmann, M.
    Molecular BioSystems 8 1775-1782 (2012)
    YggG is a conserved lipoprotein localized to the outer membrane of Gram negative bacteria. Even though the expressed open reading frame has been identified previously, the Escherichia coli protein remained uncharacterized. We report that YggG of E. coli is a metalloprotease that cleaves its targets preferentially between Phe-Phe residues. Since the yggG promoter is upregulated when bacteria are subjected to media of low osmolarity, YggG was named LoiP (low osmolarity induced protease). LoiP has an intramolecular disulfide (S-S) bond that is formed even in the absence of the periplasmic oxido-reductase DsbA and proper membrane localization of LoiP can depend on another putative metalloprotease, YfgC. © 2012 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c2mb05506f
  • 2012 • 157 Do cement nanotubes exist?
    Manzano, H. and Enyashin, A.N. and Dolado, J.S. and Ayuela, A. and Frenzel, J. and Seifert, G.
    Advanced Materials 24 3239-3245 (2012)
    Using atomistic simulations, this work indicates that cement nanotubes can exist. The chemically compatible nanotubes are constructed from the two main minerals in ordinary Portland cement pastes, namely calcium hydroxide and a calcium silicate hydrate called tobermorite. These results show that such nanotubes are stable and have outstanding mechanical properties, unique characteristics that make them ideally suitable for nanoscale reinforcements of cements. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/adma.201103704
  • 2012 • 156 Enhanced electrocatalytic stability of platinum nanoparticles supported on a nitrogen-doped composite of carbon nanotubes and mesoporous titania under oxygen reduction conditions
    Masa, J. and Bordoloi, A. and Muhler, M. and Schuhmann, W. and Xia, W.
    ChemSusChem 5 523-525 (2012)
    Cheers for titania: An N-doped composite of carbon nanotubes (CNTs) and mesoporous TiO 2 is used as support for Pt nanoparticles applied in the oxygen reduction reaction. The composite Pt/N-TiO 2-CNT shows a higher stability than Pt particles on carbon black or N-doped CNTs, as indicated by accelerated stress tests of up to 2000 cycles. The enhanced stability is attributed to strong interactions between TiO 2 and Pt and a higher corrosion resistance of TiO 2 as well as CNTs. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.201100643
  • 2012 • 155 Coulomb attraction during the carpet growth mode of NaCl
    Matthaei, F. and Heidorn, S. and Boom, K. and Bertram, C. and Safiei, A. and Henzl, J. and Morgenstern, K.
    Journal of Physics Condensed Matter 24 (2012)
    The submonolayer growth of NaCl bilayer high-rectangular shaped islands on Ag(111) is investigated at around room temperature by using low temperature scanning tunneling microscopy. The growth at the step edges is preferred. Two kinds of islands are observed. They either grow with their non-polar edge at the step edge of Ag(111) or the islands overgrow in a carpet-like mode with the polar direction parallel to the edge. In the latter case, the Ag step is rearranged and considerable, while the NaCl layer is bent. This study clarifies the nature of the interaction of an alkali halide nanostructure with a metal step edge. © 2012 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0953-8984/24/35/354006
  • 2012 • 154 Solvent-Free catalytic depolymerization of cellulose to water-soluble oligosaccharides
    Meine, N. and Rinaldi, R. and Schüth, F.
    ChemSusChem 5 1449-1454 (2012)
    The use of cellulose is hampered by difficulties with breaking up the biopolymer into soluble products. Herein, we show that the impregnation of cellulosic substrates with catalytic amounts of a strong acid (e.g., H 2SO 4, HCl) is a highly effective strategy for minimizing the contact problem commonly experienced in mechanically assisted, solid-state reactions. Milling the acid-impregnated cellulose fully converts the substrate into water-soluble oligosaccharides within 2a H. In aqueous solution, soluble products are easily hydrolyzed at 130°C in 1a H, leading to 91% conversion of the glucan fraction of α-cellulose into glucose, and 96% of the xylans into xylose. Minor products are glucose dimers (8%), 5-hydroxymethylfurfural (1%) and furfural (4%). Milling practical feedstocks (e.g., wood, sugarcane bagasse, and switchgrass) also results to water-soluble products (oligosaccharides and lignin fragments). The integrated approach (solid-state depolymerization in combination with liquid-phase hydrolysis) could well hold the key to a highly efficient "entry process" in biorefinery schemes. Reactive milling: Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.201100770
  • 2012 • 153 Microgradient-heaters as tools for high-throughput experimentation
    Meyer, R. and Hamann, S. and Ehmann, M. and Thienhaus, S. and Jaeger, S. and Thiede, T. and Devi, A. and Fischer, R.A. and Ludwig, Al.
    ACS Combinatorial Science 14 531-536 (2012)
    A microgradient-heater (MGH) was developed, and its feasibility as a tool for high-throughput materials science experimentation was tested. The MGH is derived from microhot plate (MHP) systems and allows combinatorial thermal processing on the micronano scale. The temperature gradient is adjustable by the substrate material. For an Au-coated MGH membrane a temperature drop from 605 to 100 °C was measured over a distance of 965 μm, resulting in an average temperature change of 0.52 K/μm. As a proof of principle, we demonstrate the feasibility of MGHs on the example of a chemical vapor deposition (CVD) process. The achieved results show discontinuous changes in surface morphology within a continuous TiO 2 film. Furthermore the MGH can be used to get insights into the energetic relations of film growth processes, giving it the potential for microcalorimetry measurements. © 2012 American Chemical Society.
    view abstractdoi: 10.1021/co3000488
  • 2012 • 152 Self-assembled iron oxide nanoparticle multilayer: X-ray and polarized neutron reflectivity
    Mishra, D. and Benitez, M.J. and Petracic, O. and Badini Confalonieri, G.A. and Szary, P. and Brüssing, F. and Theis-Bröhl, K. and Devishvili, A. and Vorobiev, A. and Konovalov, O. and Paulus, M. and Sternemann, C. and Toperverg...
    Nanotechnology 23 (2012)
    We have investigated the structure and magnetism of self-assembled, 20nm diameter iron oxide nanoparticles covered by an oleic acid shell for scrutinizing their structural and magnetic correlations. The nanoparticles were spin-coated on an Si substrate as a single monolayer and as a stack of 5ML forming a multilayer. X-ray scattering (reflectivity and grazing incidence small-angle scattering) confirms high in-plane hexagonal correlation and a good layering property of the nanoparticles. Using polarized neutron reflectivity we have also determined the long range magnetic correlations parallel and perpendicular to the layers in addition to the structural ones. In a field of 5kOe we determine a magnetization value of about 80% of the saturation value. At remanence the global magnetization is close to zero. However, polarized neutron reflectivity reveals the existence of regions in which magnetic moments of nanoparticles are well aligned, while losing order over longer distances. These findings confirm that in the nanoparticle assembly the magnetic dipoledipole interaction is rather strong, dominating the collective magnetic properties at room temperature. © 2012 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0957-4484/23/5/055707
  • 2012 • 151 The effect of ionic strength, temperature, and pressure on the interaction potential of dense protein solutions: From nonlinear pressure response to protein crystallization
    Möller, J. and Schroer, M.A. and Erlkamp, M. and Grobelny, S. and Paulus, M. and Tiemeyer, S. and Wirkert, F.J. and Tolan, M. and Winter, R.
    Biophysical Journal 102 2641-2648 (2012)
    Understanding the intermolecular interaction potential, V(r), of proteins under the influence of temperature, pressure, and salt concentration is essential for understanding protein aggregation, crystallization, and protein phase behavior in general. Here, we report small-angle x-ray scattering studies on dense lysozyme solutions of high ionic strength as a function of temperature and pressure. We show that the interaction potential changes in a nonlinear fashion over a wide range of temperatures, salt, and protein concentrations. Neither temperature nor protein and salt concentration lead to marked changes in the pressure dependence of V(r), indicating that changes of the water structure dominate the pressure dependence of the intermolecular forces. Furthermore, by analysis of the temperature, pressure, and ionic strength dependence of the normalized second virial coefficient, b2, we show that the interaction can be fine-tuned by pressure, which can be used to optimize b 2 values for controlled protein crystallization. © 2012 Biophysical Society.
    view abstractdoi: 10.1016/j.bpj.2012.04.043
  • 2012 • 150 Lanthanide(III) complexes of bis-semicarbazone and bis-imine-substituted phenanthroline ligands: Solid-state structures, photophysical properties, and anion sensing
    Nadella, S. and Selvakumar, P.M. and Suresh, E. and Subramanian, P.S. and Albrecht, M. and Giese, M. and Fröhlich, R.
    Chemistry - A European Journal 18 16784-16792 (2012)
    Phenanthroline-based hexadentate ligands L1 and L2 bearing two achiral semicarbazone or two chiral imine moieties as well as the respective mononuclear complexes incorporating various lanthanide ions, such as LaIII, EuIII, TbIII, LuIII, and YIII metal ions, were synthesized, and the crystal structures of [ML1Cl3] (M=LaIII, EuIII, Tb III, LuIII, or YIII) complexes were determined. Solvent or water molecules act as coligands for the rare-earth metals in addition to halide anions. The big LnIII ion exhibits a coordination number (CN) of 10, whereas the corresponding EuIII, TbIII, LuIII, and YIII centers with smaller ionic radii show CN=9. Complexes of L2, namely [ML2Cl3] (M=EuIII, TbIII, LuIII, or YIII) ions could also be prepared. Only the complex of EuIII showed red luminescence, whereas all the others were nonluminescent. The emission properties of the Eu derivative can be applied as a photophysical signal for sensing various anions. The addition of phosphate anions leads to a unique change in the luminescence behavior. As a case study, the quenching behavior of adenosine-5′-triphosphate (ATP) was investigated at physiological pH value in an aqueous solvent. A specificity of the sensor for ATP relative to adenosine-5′-diphosphate (ADP) and adenosine-5′-monophosphate (AMP) was found. 31P NMR spectroscopic studies revealed the formation of a [EuL2(ATP)] coordination species. Illuminating the ion: Hexadentate bis-semicarbazone-based achiral and bis-imine chiral ligands of phenathroline together with their respective lanthanide complexes were synthesized. The crystal structures obtained for bis- semicarbazone-based LnIII complexes reveal coordination numbers of 9 and 10. Among the bis-imine chiral complexes, a luminescent EuIII complex was investigated for sensing various anions, and selectivity towards adenosine-5′-triphosphate (ATP) was achieved in an aqueous medium (see picture). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/chem.201201705
  • 2012 • 149 Mesoporous nitrogen-rich carbon materials as catalysts for the oxygen reduction reaction in alkaline solution
    Nagaiah, T.C. and Bordoloi, A. and Sánchez, M.D. and Muhler, M. and Schuhmann, W.
    ChemSusChem 5 637-641 (2012)
    ORR MNC, FTW! Mesoporous nitrogen-rich carbon (MNC) materials are synthesized by using polymer-loaded SBA-15 pyrolyzed at different temperatures. The activity and stability of the catalysts in the oxygen reduction reaction (ORR) are investigated by using cyclic voltammetry and rotating-disk electrode measurements. The MNC material pyrolyzed at 800 °C exhibits a high electrocatalytic activity towards the ORR in alkaline medium. © 2012 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.201100284
  • 2012 • 148 Interface of nanoparticle-coated electropolished stents
    Neumeister, A. and Bartke, D. and Bärsch, N. and Weingärtner, T. and Guetaz, L. and Montani, A. and Compagnini, G. and Barcikowski, S.
    Langmuir 28 12060-12066 (2012)
    Nanostructures entail a high potential for improving implant surfaces, for instance, in stent applications. The electrophoretic deposition of laser-generated colloidal nanoparticles is an appropriate tool for creating large-area nanostructures on surfaces. Until now, the bonding and characteristics of the interface between deposited nanoparticles and the substrate surface has not been known. It is investigated using X-ray photoelectron spectroscopy, Auger electron spectroscopy, and transmission electron microscopy to characterize an electropolished NiTi stent surface coated by laser-generated Au and Ti nanoparticles. The deposition of elemental Au and Ti nanoparticles is observed on the total 3D surface. Ti-coated samples are composed of Ti oxide and Ti carbide because of nanoparticle fabrication and the coating process carried out in 2-propanol. The interface between nanoparticles and the electropolished surface consists of a smooth, monotone elemental depth profile. The interface depth is higher for the Ti nanoparticle coating than for the Au nanoparticle coating. This smooth depth gradient of Ti across the coating-substrate intersection and the thicker interface layer indicate the hard bonding of Ti-based nanoparticles on the surface. Accordingly, electron microscopy reveals nanoparticles adsorbed on the surface without any sorption-blocking intermediate layer. The physicomechanical stability of the bond may benefit from such smooth depth gradients and direct, ligand-free contact. This would potentially increase the coating stability during stent application. © 2012 American Chemical Society.
    view abstractdoi: 10.1021/la300308w
  • 2012 • 147 Preparation and comparative release characteristics of three anthocyanin encapsulation systems
    Oidtmann, J. and Schantz, M. and Mäder, K. and Baum, M. and Berg, S. and Betz, M. and Kulozik, U. and Leick, S. and Rehage, H. and Schwarz, K. and Richling, E.
    Journal of Agricultural and Food Chemistry 60 844-851 (2012)
    Bilberries (Vaccinium myrtillus L.) and their major polyphenolic constituents, anthocyanins, have preventive activities inter alia against colon cancer and inflammatory bowel diseases. However, anthocyanins are sensitive to environmental conditions; thus their bioavailability in the gastrointestinal tract is an important determinant of their in vivo activity. In the study reported here, the potential benefits of encapsulating an anthocyanin rich bilberry extract (BE) on anthocyanin stability were investigated. Nonencapsulated BE and three different BE loaded microcapsule systems were incubated in simulated gastric fluid (SGF) and fed state simulated intestinal fluid (FeSSIF). After exposure to these media, released anthocyanins were identified and quantified by HPLC with UV/Vis detection. Although a rapid release of anthocyanins was observed within the first 20 min, encapsulation of anthocyanins doubled the amount of available anthocyanins after 150 min of incubation. These results illustrate the ability of encapsulation to inhibit early degradation of anthocyanins in the intestinal system. © 2011 American Chemical Society.
    view abstractdoi: 10.1021/jf2047515
  • 2012 • 146 All-optical tunability of microdisk lasers via photo-adressable polyelectrolyte functionalization
    Piegdon, K.A. and Lexow, M. and Grundmeier, G. and Kitzerow, H.-S. and Pärschke, K. and Mergel, D. and Reuter, D. and Wieck, A.D. and Meier, C.
    Optics Express 20 6060-6067 (2012)
    Photoactive materials are highly promising candidates for novel applications as they enable all-optical control of photonic devices. Photochromic molecules exhibit a reversible change of their dielectric function upon irradiation with light of proper wavelength. The trans- and cis-isomers of azobenzene exhibit different absorption properties due to the effect of the configuration on the polarizability of the molecule. Here, we introduce a novel molecular/semiconductor hybrid device which is fully tunable by all-optical means via the integration of a semiconductor microdisk into a photo-adressable polyelectrolyte material. We demonstrate that such polyelectrolyte superlattices can be used to tune semiconductor photonic resonators with high precision and without any significant degeneration of device performance. Moreover, we demonstrate an all-optically tunable laser based on this hybrid concept. © 2012 Optical Society of America.
    view abstractdoi: 10.1364/OE.20.006060
  • 2012 • 145 Experimental studies of Debye-like process and structural relaxation in mixtures of 2-ethyl-1-hexanol and 2-ethyl-1-hexyl bromide
    Preu, M. and Gainaru, C. and Hecksher, T. and Bauer, S. and Dyre, J.C. and Richert, R. and Böhmer, R.
    Journal of Chemical Physics 137 (2012)
    Binary solutions of 2-ethyl-1-hexanol (2E1H) with 2-ethyl-1-hexyl bromide (2E1Br) are investigated by means of dielectric, shear mechanical, near-infrared, and solvation spectroscopy as well as dielectrically monitored physical aging. For moderately diluted 2E1H the slow Debye-like process, which dominates the dielectric spectra of the neat monohydroxy alcohol, separates significantly from the α-relaxation. For example, the separation in equimolar mixtures amounts to four decades in frequency. This situation of highly resolved processes allows one to demonstrate unambiguously that physical aging is governed by the α-process, but even under these ideal conditions the Debye process remains undetectable in shear mechanical experiments. Furthermore, the solvation experiments show that under constant charge conditions the microscopic polarization fluctuations take place on the time scale of the structural process. The hydrogen-bond populations monitored via near-infrared spectroscopy indicate the presence of a critical alcohol concentration, x c ≈ 0.5-0.6, thereby confirming the dielectric data. In the pure bromide a slow dielectric process of reduced intensity is present in addition to the main relaxation. This is taken as a sign of intermolecular cooperativity probably mediated via halogen bonds. © 2012 American Institute of Physics.
    view abstractdoi: 10.1063/1.4755754
  • 2012 • 144 Nanolattices of switchable DNA-based motors
    Saccà, B. and Siebers, B. and Meyer, R. and Bayer, M. and Niemeyer, C.M.
    Small 8 3000-3008 (2012)
    Miniaturization is an important aspect of device fabrication. Despite the advancements of modern top-down approaches, scaling-down to the sub-nanometer size is still a challenge. As an alternative, bottom-up approaches, such as the use of DNA as an engineering material, are therefore emerging, allowing control of matter at the single-molecule level. A DNA-based self-assembly method for the construction of switchable DNA devices is descrbied here based on G-quadruplex moieties, which are patterned on quasi-planar DNA arrays with nanoscale precision. The reversible switching of the devices is triggered by addition of DNA sequences ('fuels') and translated into linear extension/contractile movements. The conformational change of the devices was visualized by atomic force microscopy and FRET spectroscopy. Steady state fluorescence spectroscopy indicated that scaffolding of the G4 motors to either individual tiles or extended superlattices had no significant impact on the switching and optical performance of the system. However, time-resolved spectroscopy revealed that ordering in the microstructural environment enhances the fraction of molecules subject to FRET. Altogether, our study confirms that DNA superstructures are well-suited scaffolds for accommodation of mechanically switchable units and thus opens the door to the development of more sophisticated nanomechanical devices. Ordered planar nanoarrays bearing DNA-responsive devices are produced by DNA self-assembly procedures. The nanomotors display extension and contraction movements in response to addition of DNA fuels with efficient cycling operation even after repetitive cycles. This DNA-based assembly of nanomechanical units offers full control over the spatial arrangement of each single molecule and opens the door to the development of more sophisticated nanomechanical devices. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/smll.201200703
  • 2012 • 143 Protein recognition: Calixarene connection
    Schrader, T.
    Nature Chemistry 4 519-520 (2012)
    doi: 10.1038/nchem.1386
  • 2012 • 142 Hypothesis: Origin of Life in Deep-Reaching Tectonic Faults
    Schreiber, U. and Locker-Grütjen, O. and Mayer, C.
    Origins of Life and Evolution of Biospheres 42 47-54 (2012)
    The worldwide discussion on the origin of life encounters difficulties when it comes to estimate the conditions of the early earth and to define plausible environments for the development of the first complex organic molecules. Until now, the role of the earth's crust has been more or less ignored. In our opinion, deep-reaching open, interconnected tectonic fault systems may provide possible reaction habitats ranging from nano- to centimetre and even larger dimensions for the formation of prebiotic molecules. In addition to the presence of all necessary raw materials including phosphate, as well as variable pressure and temperature conditions, we suggest that supercritical CO 2 as a nonpolar solvent could have played an important role. A hypothetical model for the origin of life is proposed which will be used to design crucial experiments for the model's verification. Because all proposed processes could still occur in tectonic faults at the present time, it may be possible to detect and analyse the formation of prebiotic molecules in order to assess the validity of the proposed hypothesis. © 2012 Springer Science+Business Media B.V.
    view abstractdoi: 10.1007/s11084-012-9267-4
  • 2012 • 141 Exploring the thermodynamic derivatives of the structure factor of dense protein solutions
    Schroer, M.A. and Tolan, M. and Winter, R.
    Physical Chemistry Chemical Physics 14 9486-9491 (2012)
    Using small-angle X-ray scattering data of concentrated solutions of the protein lysozyme taken at different pressures and temperatures, the isothermal pressure derivative and the isobaric temperature derivative of the structure factor S(q) were determined. The pressure derivative of S(q) allows us to test various models for the triplet correlation function g 3. Significant differences were found in comparison to simple liquids reflecting the more complex interaction potential in dense protein solutions. © 2012 the Owner Societies.
    view abstractdoi: 10.1039/c2cp41041a
  • 2012 • 140 Cross-amyloid interaction of Aβ and IAPP at lipid membranes
    Seeliger, J. and Evers, F. and Jeworrek, C. and Kapoor, S. and Weise, K. and Andreetto, E. and Tolan, M. and Kapurniotu, A. and Winter, R.
    Angewandte Chemie - International Edition 51 679-683 (2012)
    Membrane controlled protein assembly: A study of the amyloid interaction of the islet amyloid polypeptide (IAPP), β-amyloid (Aβ), and a mixture of both with an anionic model raft membrane showed the dominant effect of IAPP on the aggregation process and on the hydrogen-bonding pattern of the assemblies present in the mixture (see picture). The analysis of the interaction of Aβ with IAPP-GI-a non-amyloidogenic IAPP mimic-confirmed these findings. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201105877
  • 2012 • 139 DFT calculations suggest a new type of self-protection and self-inhibition mechanism in the mammalian heme enzyme myeloperoxidase: Nucleophilic addition of a functional water rather than one-electron reduction
    Sicking, W. and Somnitz, H. and Schmuck, C.
    Chemistry - A European Journal 18 10937-10948 (2012)
    The mammalian heme enzyme myeloperoxidase (MPO) catalyzes the reaction of Cl- to the antimicrobial-effective molecule HOCl. During the catalytic cycle, a reactive intermediate "Compound I" (Cpd I) is generated. Cpd I has the ability to destroy the enzyme. Indeed, in the absence of any substrate, Cpd I decays with a half-life of 100 ms to an intermediate called Compound II (Cpd II), which is typically the one-electron reduced Cpd I. However, the nature of Cpd II, its spectroscopic properties, and the source of the additional electron are only poorly understood. On the basis of DFT and time-dependent (TD)-DFT quantum chemical calculations at the PBE0/6-31G* level, we propose an extended mechanism involving a new intermediate, which allows MPO to protect itself from self-oxidation or self-destruction during the catalytic cycle. Because of its similarity in electronic structure to Cpd II, we named this intermediate Cpd IIa'. However, the suggested mechanism and our proposed functional structure of Cpd IIa' are based on the hypothesis that the heme is reduced by charge separation caused by reaction with a water molecule, and not, as is normally assumed, by the transfer of an electron. In the course of this investigation, we found a second intermediate, the reduced enzyme, towards which the new mechanism is equally transferable. In analogy to Cpd II′, we named it FeIIa'. The proposed new intermediates Cpd IIa' and FeIIa' allow the experimental findings, which have been well documented in the literature for decades but not so far understood, to be explained for the first time. These encompass a) the spontaneous decay of Cpd I, b) the unusual (chlorin-like) UV/Vis, circular dichroism (CD), and resonance Raman spectra, c) the inability of reduced MPO to bind CO, d) the fact that MPO-Cpd II reduces SCN- but not Cl-, and e) the experimentally observed auto-oxidation/auto-reduction features of the enzyme. Our new mechanism is also transferable to cytochromes, and could well be viable for heme enzymes in general. Heme mechanisms explained: Direct visual comparison with Cpd II demonstrates that Cpd II′ is a one-electron reduced intermediate with respect to the heme system. In both cases an electron is transferred: in Cpd II from an external donor, and in Cpd II′ through charge separation caused by reaction with a water molecule (see figure). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/chem.201103477
  • 2012 • 138 Fluorescence labels in kinases: A high-throughput kinase binding assay for the identification of DFG-out binding ligands
    Simard, J.R. and Rauh, D.
    Methods in Molecular Biology 800 95-117 (2012)
    Despite the hundreds of kinase inhibitors currently in discovery and pre-clinical phases, the number of kinase inhibitors which have been approved and are on the market remains low by comparison. This discrepancy reflects the challenges which accompany the development of kinase inhibitors which are relatively specific and less toxic. Targeting protein kinases with ATP-competitive inhibitors has been the classical approach to inhibiting kinase activity, but the highly conserved nature of the ATP-binding site contributes to poor inhibitor selectivity, issues which have particularly hampered the development of novel kinase inhibitors. We developed a high-throughput screening technology that can discriminate for inhibitors which stabilize the inactive "DFG-out" kinase conformation by binding within an allosteric pocket adjacent to the ATP-binding site. Here, we describe how to use this approach to measure the K d of ligands, as well as how to kinetically characterize the binding and dissociation of ligands to the kinase. We also describe how this technology can be used to rapidly screen small molecule libraries at high throughput. © 2012 Springer Science+Business Media, LLC.
    view abstractdoi: 10.1007/978-1-61779-349-3_8
  • 2012 • 137 Ag/ZnO nanomaterials as high performance sensors for flammable and toxic gases
    Simon, Q. and Barreca, D. and Gasparotto, A. and MacCato, C. and Tondello, E. and Sada, C. and Comini, E. and Devi, A. and Fischer, R.A.
    Nanotechnology 23 (2012)
    Ag/ZnO nanocomposites supported on polycrystalline Al 2O 3 were synthesized by an unprecedented approach combining plasma enhanced chemical vapor deposition (PE-CVD) of ZnO matrices and the subsequent deposition of Ag nanoparticles (NPs) by radio frequency (RF) sputtering. The system structure, composition and morphology were investigated by glancing incidence x-ray diffraction (GIXRD), secondary ion mass spectrometry (SIMS), field emission scanning electron microscopy (FE-SEM) and energy dispersive x-ray spectroscopy (EDXS). A tailored dispersion and distribution of silver particles could be obtained under mild conditions by the sole variation of the sputtering time. Gas sensing properties toward flammable and toxic gases, both reducing (CH 3CH 2OH, CH 3COCH 3) and oxidizing (O 3), were investigated in the temperature range 100400°C. Beside the high sensitivity, the developed sensors exhibited a response proportional to Ag content, thanks to catalytic and electronic effects promoted by silver NPs. In addition, discrimination between oxidizing and reducing analytes was enabled by a suitable choice of the adopted working temperature.
    view abstractdoi: 10.1088/0957-4484/23/2/025502
  • 2012 • 136 Molecular interactions of 2′-deoxyguanosine 5′-monophosphate with glycine in aqueous media probed via concentration and pH dependent Raman spectroscopic investigations and DFT study
    Singh, S. and Srivastava, S.K. and Donfack, P. and Schlücker, S. and Materny, A. and Asthana, B.P.
    Physical Chemistry Chemical Physics 14 14315-14324 (2012)
    In order to gain insights into nucleotide-protein interaction, the molecular interaction of glycine (Gly) with 2′-deoxyguanosine 5′-monophosphate (dGMP) was monitored in aqueous media through Raman spectroscopic measurements and density functional theory (DFT) calculations. Raman spectra of dGMP, glycine and their binary mixtures (dGMP + Gly) in aqueous media at 10 different concentrations corresponding to the dGMP:Gly molar ratios varying from 1:1 to 1:10 were recorded in the fingerprint region 2000-400 cm-1. Raman spectra of the dGMP:Gly mixture with a molar ratio of 1:3 in aqueous media at 10 different pH values starting from 1 to 10 at an interval of 1 were also recorded. The DFT calculations were performed on dGMP, glycine and their various complexes with varying number of H2O molecules in gas phase as well as in solvation using hybrid functional B3LYP employing the high level basis set 6-311+G(d,p). The variations in the observed spectral features were explained in terms of calculated optimized structures of dGMP, glycine and their various complexes with water molecules and a good spectra-structure correlation was obtained. Raman spectra of glycine in 1.2 M aqueous solution were also recorded at three pH values, 2, 6 and 10, and the subtle differences in the spectral features were correlated with the calculated Raman spectra of protonated, deprotonated and zwitterionic forms of glycine. The results also give experimental evidence rather convincingly that the zwitterionic and protonated forms of glycine are formed at pH = 6 and 2, respectively, but even at pH = 10, deprotonated glycine is not formed. An important aspect of this study is the monitoring of the interaction of dGMP with the zwitterionic form of glycine giving insightful details regarding the binding site. © 2012 the Owner Societies.
    view abstractdoi: 10.1039/c2cp41205e
  • 2012 • 135 Mass transport controlled oxygen reduction at anthraquinone modified 3D-CNT electrodes with immobilized Trametes hirsuta laccase
    Sosna, M. and Stoica, L. and Wright, E. and Kilburn, J.D. and Schuhmann, W. and Bartlett, P.N.
    Physical Chemistry Chemical Physics 14 11882-11885 (2012)
    Carbon nanotubes covalently modified with anthraquinone were used as an electrode for the immobilization of Trametes hirsuta laccase. The adsorbed laccase is capable of oxygen reduction at a mass transport controlled rate (up to 3.5 mA cm-2) in the absence of a soluble mediator. The storage and operational stability of the electrode are excellent. This journal is © 2012 the Owner Societies.
    view abstractdoi: 10.1039/c2cp41588g
  • 2012 • 134 NMR and conductivity studies of the mixed glass former effect in lithium borophosphate glasses
    Storek, M. and Böhmer, R. and Martin, S.W. and Larink, D. and Eckert, H.
    Journal of Chemical Physics 137 (2012)
    Alkali ion charge transport has been studied in a series of mixed glass former lithium borophosphate glasses of composition 0.33Li 2O 0.67xB 2O 3 (1 - x)P 2O 5. The entire concentration range, 0.0 x 1.0, from pure glassy Li 2P 4O 11 to pure glassy Li 2B 4O 7 has been examined while keeping the molar fraction of Li 2O constant. Electrical conductivity measurements and nuclear magnetic resonance techniques such as spin relaxometry, line shape analysis, and stimulated-echo spectroscopy were used to examine the temperature and frequency dependence of the Li ion motion over wide ranges of time scale and temperature. By accurately determining motional time scales and activation energies over the entire composition range the ion dynamics and the charge transport are found to be fastest if the borate and the phosphate fractions are similar. The nonlinear variation of the charge conduction, the most notable feature of the mixed glass former effect, is discussed in terms of the composition dependence of network former units which determine the local glass structure. © 2012 American Institute of Physics.
    view abstractdoi: 10.1063/1.4754664
  • 2012 • 133 Impact of metal nanoparticles on germ cell viability and functionality
    Taylor, U. and Barchanski, A. and Kues, W. and Barcikowski, S. and Rath, D.
    Reproduction in Domestic Animals 47 359-368 (2012)
    Metal nanoparticles play an increasing role in consumer products, biomedical applications and in the work environment. Therefore, the effects of nanomaterials need to be properly understood. This applies especially to their potential reproductive toxicology (nanoreprotoxicity), because any shortcomings in this regard would be reflected into the next generation. This review is an attempt to summarize the current knowledge regarding the effects of nanoparticles on reproductive outcomes. A comprehensive collection of significant experimental nanoreprotoxicity data is presented, which highlight how the toxic effect of nanoparticles can be influenced, not only by the particles' chemical composition, but also by particle size, surface modification, charge and to a considerable extent on the experimental set-up. The period around conception is characterized by considerable cytological and molecular restructuring and is therefore particularly sensitive to disturbances. Nanoparticles are able to penetrate through biological barriers into reproductive tissue and at least can have an impact on sperm vitality and function as well as embryo development. Particularly, further investigations are urgently needed on the repetitively shown effect of the ubiquitously used titanium dioxide nanoparticles on the development of the nervous system. It is recommended that future research focuses more on the exact mechanism behind the observed effects, because such information would facilitate the production of nanoparticles with increased biocompatibility. © 2012 Blackwell Verlag GmbH.
    view abstractdoi: 10.1111/j.1439-0531.2012.02099.x
  • 2012 • 132 Conditioning of surfaces by macromolecules and its implication for the settlement of zoospores of the green alga Ulva linza
    Thome, I. and Pettitt, M.E. and Callow, M.E. and Callow, J.A. and Grunze, M. and Rosenhahn, A.
    Biofouling 28 501-510 (2012)
    Conditioning, ie the adsorption of proteins and other macromolecules, is the first process that occurs in the natural environment once a surface is immersed in seawater, but no information is available either regarding the conditioning of surfaces by artificial seawater or whether conditioning affects data obtained from laboratory assays. A range of self-assembled monolayers (SAMs) with different chemical terminations was used to investigate the time-dependent formation of conditioning layers in commercial and self-prepared artificial seawaters. Subsequently, these results were compared with conditioning by solutions in which zoospores of the green alga Ulva linza had been swimming. Spectral ellipsometry and contact angle measurements as well as infrared reflection absorption spectroscopy (IRRAS) were used to reveal the thickness and chemical composition of the conditioning layers. The extent that surface preconditioning affected the settlement of zoospores of U. linza was also investigated. The results showed that in standard spore settlement bioassays (45-60 min), the influence of a molecular conditioning layer is likely to be small, although more substantial effects are possible at longer settlement times. © 2012 Copyright Taylor and Francis Group, LLC.
    view abstractdoi: 10.1080/08927014.2012.689288
  • 2012 • 131 ITRAQ data interpretation
    Vaudel, M. and Burkhart, J.M. and Zahedi, R.P. and Martens, L. and Sickmann, A.
    Methods in Molecular Biology 893 501-509 (2012)
    Quantitative proteomic analysis can help elucidating unexplored biological questions; it, however, relies on highly reproducible experiments and reliable data processing. Among the existing strategies, iTRAQ is known as an easy to use method allowing relative comparison of up to eight multiplexed samples. Once the data is acquired it is important that the final protein quantification reflects the actual amounts in the samples. Data interpretation must thus be achieved with a constant focus on quality. Here, we describe a workflow for processing iTRAQ data in user-friendly environments with emphasis on quality control. © 2012 Springer Science+Business Media, LLC.
    view abstractdoi: 10.1007/978-1-61779-885-6_30
  • 2012 • 130 Evaluation of the catalytic performance of gas-evolving electrodes using local electrochemical noise measurements
    Zeradjanin, A.R. and Ventosa, E. and Bondarenko, A.S. and Schuhmann, W.
    ChemSusChem 5 1905-1911 (2012)
    Characterization of gas evolution reactions at the electrode/electrolyte boundary is often difficult due to the dynamic behavior of interfacial processes. Electrochemical noise measurements determined by scanning electrochemical microscopy were used to characterize Cl 2 evolution at gas-evolving electrodes (GEEs). Analysis of the electrochemical noise is a powerful method to evaluate the efficiency of the catalyst layer at a GEE. The high sensitivity of the developed measurement system enabled accurate monitoring of the current fluctuations caused by gas-bubble detachment from the electrode surface. Fourier transform analysis of the obtained current responses allows extraction of the characteristic frequency, which is the main parameter of the macrokinetics of GEEs. The characteristic frequency was used as part of a methodology to evaluate the catalyst performance and, in particular, to estimate the fraction of the catalyst layer that is active during the gas evolution reaction. Tip of the iceberg: Positioned scanning electrochemical microscopy tips are used to determine the characteristic frequency of gas-bubble detachment from ruthenium-based dimensionally stable anodes at different applied potentials (see picture). Geometrical factors and optimized microstructures of the electrode surface are essential for improving the overall catalytic activity for industrial applications. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.201200262
  • 2012 • 129 Role of Water in the Chlorine Evolution Reaction at RuO 2-Based Electrodesa-Understanding Electrocatalysis as a Resonance Phenomenon
    Zeradjanin, A.R. and Menzel, N. and Strasser, P. and Schuhmann, W.
    ChemSusChem 5 1897-1904 (2012)
    The reaction path of the Cl 2 evolution reaction (CER) was investigated by combining electrochemical and spectroscopic methods. It is shown that oxidation and reconstruction of the catalyst surface during CER is a consequence of the interaction between RuO 2 and water. The state of the RuO 2 surface during the electrochemical reaction was analyzed in situ by using Raman spectroscopy to monitor vibrations of the crystal lattice of RuO 2 and changes in the surface concentration of the adsorbed species as a function of the electrode potential. The role of the solvent was recognized as being crucial in the formation of an oxygen-containing hydrophilic layer, which is a key prerequisite for electrocatalytic Cl 2 formation. Water (more precisely the OH adlayer) is understood not just as a medium that allows adsorption of intermediates, but also as an integral part of the intermediate formed during the electrochemical reaction. New insights into the general understanding of electrocatalysis were obtained by utilizing the vibration frequencies of the crystal lattice as a dynamic catalytic descriptor instead of thermodynamic descriptors, such as the adsorption energy of intermediates. Interpretation of the derived "volcano" curve suggests that electrocatalysis is governed by a resonance phenomenon. Water powered! The reaction path of the Cl 2 evolution reaction (CER) is investigated by combining electrochemical and spectroscopic methods. Oxidation and reconstruction of the catalyst surface during CER is a consequence of the interaction between RuO 2 and water. Interpretation of the derived volcano curve suggests that electrocatalysis is governed by a resonance phenomenon (see picture). © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.201200193
  • 2011 • 128 A guideline for atomistic design and understanding of ultrahard nanomagnets
    Antoniak, C. and Gruner, M.E. and Spasova, M. and Trunova, A.V. and Römer, F.M. and Warland, A. and Krumme, B. and Fauth, K. and Sun, S. and Entel, P. and Farle, M. and Wende, H.
    Nature Communications 2 (2011)
    Magnetic nanoparticles are of immense current interest because of their possible use in biomedical and technological applications. Here we demonstrate that the large magnetic anisotropy of FePt nanoparticles can be significantly modified by surface design. We employ X-ray absorption spectroscopy offering an element-specific approach to magnetocrystalline anisotropy and the orbital magnetism. Experimental results on oxide-free FePt nanoparticles embedded in Al are compared with large-scale density functional theory calculations of the geometric- and spin-resolved electronic structure, which only recently have become possible on world-leading supercomputer architectures. The combination of both approaches yields a more detailed understanding that may open new ways for a microscopic design of magnetic nanoparticles and allows us to present three rules to achieve desired magnetic properties. In addition, concrete suggestions of capping materials for FePt nanoparticles are given for tailoring both magnetocrystalline anisotropy and magnetic moments. © 2011 Macmillan Publishers Limited. All rights reserved.
    view abstractdoi: 10.1038/ncomms1538
  • 2011 • 127 Golden Perspective: Application of Laser-Generated Gold Nanoparticle Conjugates in Reproductive Biology
    Barchanski, A. and Taylor, U. and Klein, S. and Petersen, S. and Rath, D. and Barcikowski, S.
    Reproduction in Domestic Animals 46 42-52 (2011)
    Contents: The current demand for female calves has grown rapidly and controlling the sex of offspring provides an economically flexible management for the livestock producer. The only functioning method of efficiently producing separate populations of X and Y sperm in mammals is based on relative DNA differentiation by high-speed flow cytometry. In this context, gold nanoparticles conjugated to sex chromosome-specific moieties display promising application as novel fluorophor-alternative for the high-throughput screening, since they feature no photo bleaching, high quantum yield, good biocompatibility and the possibility of non-destructive membrane penetration. Especially, gold nanoparticles fabricated by pulsed laser ablation are in the recent focus of interest, due to excellent biocompatibility, fabrication-dependent, tuneable particle size as well as surface charge and ease of (bio)-functionalization with a remarkably strong ligand binding. For the purpose of our studies functionalized gold nanoparticles may be used as novel markers for sex-sorting of mammalian sperm and, depending on the selected probe, also for the selection of sperm with heritable DNA-sequences interesting for animal breeding. © 2011 Blackwell Verlag GmbH.
    view abstractdoi: 10.1111/j.1439-0531.2011.01844.x
  • 2011 • 126 Structural and magnetic characterization of self-assembled iron oxide nanoparticle arrays
    Benitez, M.J. and Mishra, D. and Szary, P. and Badini Confalonieri, G.A. and Feyen, M. and Lu, A.H. and Agudo, L. and Eggeler, G. and Petracic, O. and Zabel, H.
    Journal of Physics Condensed Matter 23 (2011)
    We report about a combined structural and magnetometric characterization of self-assembled magnetic nanoparticle arrays. Monodisperse iron oxide nanoparticles with a diameter of 20nm were synthesized by thermal decomposition. The nanoparticle suspension was spin-coated on Si substrates to achieve self-organized arrays of particles and subsequently annealed at various conditions. The samples were characterized by x-ray diffraction, and bright and dark field high resolution transmission electron microscopy. The structural analysis is compared to magnetization measurements obtained by superconducting quantum interference device magnetometry. We can identify either multi-phase FexO/γ-Fe2O3 or multi-phase Fe xO/Fe3O4 nanoparticles. The Fe xO/γ-Fe2O3 system shows a pronounced exchange bias effect which explains the peculiar magnetization data found for this system. © 2011 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0953-8984/23/12/126003
  • 2011 • 125 Quantitative detection of C-deuterated drugs by CARS microscopy and Raman microspectroscopy
    Bergner, G. and Albert, C.R. and Schiller, M. and Bringmann, G. and Schirmeister, T. and Dietzek, B. and Niebling, S. and Schlücker, S. and Popp, J.
    Analyst 136 3686-3693 (2011)
    The introduction of carbon-deuterium (C-D) bonds into drug compounds by organic synthesis is a non-invasive labelling approach, which does not alter the chemical and physiological properties of the drug itself. C-deuterated drugs exhibit characteristic vibrational signatures in the C-D stretching region around 2100-2300 cm -1, which avoids spectral interference with contributions from a complex biological environment. In this paper, the quantitative detection of C-deuterated drugs by Raman microspectroscopy and single-band CARS microscopy is examined. Concentration-dependent studies on drugs with aliphatic and aromatic C-D moieties were performed in a two-channel microfluidic chip, using the corresponding non-deuterated (C-H) isotopologues as an internal reference. © 2011 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c0an00956c
  • 2011 • 124 Effects of counterpoise correction and basis set extrapolation on the MP2 geometries of hydrogen bonded dimers of ammonia, water, and hydrogen fluoride
    Boese, A.D. and Jansen, G. and Torheyden, M. and Höfener, S. and Klopper, W.
    Physical Chemistry Chemical Physics 13 1230-1238 (2011)
    We study the combined effects of counterpoise correction and basis set extrapolation on the second-order Møller-Plesset (MP2) geometries of three hydrogen bonded dimers, namely (NH3)2, (H 2O)2 and (HF)2. For (NH3) 2, we study three characteristic structures on its potential energy surface. In addition, we look at the basis set convergence when diffuse functions on the hydrogen atoms are left out, as well as the errors introduced by including core correlation with valence-only correlation-consistent basis sets. Overall, the counterpoise-corrected and extrapolated geometries appear to be very reliable and are in convincing agreement with the geometries from explicitly correlated MP2-F12 calculations. Obtaining geometries with errors of less than 0.001 Ångstrom and 0.5 degrees compared to the basis set limit is, however, even with these advanced methods a difficult task. © the Owner Societies 2011.
    view abstractdoi: 10.1039/c0cp01493a
  • 2011 • 123 Photomodulation of the magnetisation of Co nanocrystals decorated with Rhodamine B
    Comesaña-Hermo, M. and Estivill, R. and Ciuculescu, D. and Amiens, C. and Farle, M. and Batat, P. and Jonusauskas, G. and McClenaghan, N.D. and Lecante, P. and Tardin, C. and Mazeres, S.
    ChemPhysChem 12 2915-2919 (2011)
    How exciting! Upon excitation of Rhodamine B with visible light in magnetic Co nanocrystal-Rhodamine B nanocomposites, electron transfer from the nanocrystal to the dye is evidenced as well as an increase in magnetisation (see picture), affording a new access to photomodulation of the magnetic properties of nanocrystal assemblies. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cphc.201100616
  • 2011 • 122 Shape transformation mechanism of silver nanorods in aqueous solution
    Damm, C. and Segets, D. and Yang, G. and Vieweg, B.F. and Spiecker, E. and Peukert, W.
    Small 7 147-156 (2011)
    The spontaneous shape transformation of silver nanorods with an initial length of several hundred nanometers towards spherical particle shapes in aqueous solution is investigated by means of scanning electron microscopy, UV-vis absorption spectroscopy, anodic stripping voltammetry, and high-resolution transmission electron microscopy (HRTEM). The consolidation of the results reveals an increase in the particle number density with time. Moreover, HRTEM image analysis along the cross section of the rods evidences the presence of fivefold twinning defects which extend along the whole rod length. According to the analytical model of Monk et al. this kind of rod structure is only thermodynamically stable if the rod length is below a critical value at a given diameter. The rods investigated in the present work do not fulfill the stability criterion as they exceed the critical length. Thus, the rods decay into smaller "nanobuns" and defective as well as defect-free spheres. A mechanism based on findings from the literature, HRTEM image analysis of former rods, transition states, and the final particle structures is proposed. The defects along the surface are seen as starting points for the dissolution of material, which is reintegrated into the solid phase by homogeneous as well as heterogeneous nucleation and growth. The decay process of silver nanorods in aqueous suspension is investigated. During ageing the aspect ratio decreases with time whereas the absolute particle number increases. Defects play a decisive role in rod decay and underline how crystal structure influences particle shape. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/smll.201001600
  • 2011 • 121 Templated synthesis of shape-controlled, ordered TiO 2 cage structures
    Deng, Y. and Tüysüz, H. and Henzie, J. and Yang, P.
    Small 7 2037-2040 (2011)
    Based on a combination of colloidal self-assembly and atomic layer deposition, a facile approach is developed to create novel, high-quality, ordered cage structures of anatase TiO 2 with shape and morphology control using Ag nanocrystals of different shapes as templates. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/smll.201100579
  • 2011 • 120 Construction of uricase-overproducing strains of Hansenula polymorpha and its application as biological recognition element in microbial urate biosensor
    Dmytruk, K.V. and Smutok, O.V. and Dmytruk, O.V. and Schuhmann, W. and Sibirny, A.A.
    BMC Biotechnology 11 (2011)
    Background: The detection and quantification of uric acid in human physiological fluids is of great importance in the diagnosis and therapy of patients suffering from a range of disorders associated with altered purine metabolism, most notably gout and hyperuricaemia. The fabrication of cheap and reliable urate-selective amperometric biosensors is a challenging task.Results: A urate-selective microbial biosensor was developed using cells of the recombinant thermotolerant methylotrophic yeast Hansenula polymorpha as biorecognition element. The construction of uricase (UOX) producing yeast by over-expression of the uricase gene of H. polymorpha is described. Following a preliminary screening of the transformants with increased UOX activity in permeabilized yeast cells the optimal cultivation conditions for maximal UOX yield namely a 40-fold increase in UOX activity were determined.The UOX producing cells were coupled to horseradish peroxidase and immobilized on graphite electrodes by physical entrapment behind a dialysis membrane. A high urate selectivity with a detection limit of about 8 μM was found.Conclusion: A strain of H. polymorpha overproducing UOX was constructed. A cheap urate selective microbial biosensor was developed. © 2011 Dmytruk et al; licensee BioMed Central Ltd.
    view abstractdoi: 10.1186/1472-6750-11-58
  • 2011 • 119 Comparison of nanoparticle-mediated transfection methods for DNA expression plasmids: Efficiency and cytotoxicity
    Durán, M.C. and Willenbrock, S. and Barchanski, A. and Müller, J.-M.V. and Maiolini, A. and Soller, J.T. and Barcikowski, S. and Nolte, I. and Feige, K. and Murua Escobar, H.
    Journal of Nanobiotechnology 9 (2011)
    Background: Reproducibly high transfection rates with low methodology-induced cytotoxic side effects are essential to attain the required effect on targeted cells when exogenous DNA is transfected. Different approaches and modifications such as the use of nanoparticles (NPs) are being evaluated to increase transfection efficiencies. Several studies have focused on the attained transfection efficiency after NP-mediated approaches. However, data comparing toxicity of these novel approaches with conventional methods is still rare.Transfection efficiency and methodology-induced cytotoxicity were analysed after transfection with different NP-mediated and conventional approaches. Two eukaryotic DNA-expression-plasmids were used to transfect the mammalian cell line MTH53A applying six different transfection protocols: conventional transfection reagent (FuGENE HD, FHD), FHD in combination with two different sizes of stabilizer-free laser-generated AuNPs (PLAL-AuNPs_S1,_S2), FHD and commercially available AuNPs (Plano-AuNP), and two magnetic transfection protocols. 24 h post transfection efficiency of each protocol was analysed using fluorescence microscopy and GFP-based flow cytometry. Toxicity was assessed measuring cell proliferation and percentage of propidium iodide (PI%) positive cells. Expression of the respective recombinant proteins was evaluated by immunofluorescence.Results: The addition of AuNPs to the transfection protocols significantly increased transfection efficiency in the pIRES-hrGFPII-eIL-12 transfections (FHD: 16%; AuNPs mean: 28%), whereas the magnet-assisted protocols did not increase efficiency. Ligand-free PLAL-AuNPs had no significant cytotoxic effect, while the ligand-stabilized Plano-AuNPs induced a significant increase in the PI% and lower cell proliferation. For pIRES-hrGFPII-rHMGB1 transfections significantly higher transfection efficiency was observed with PLAL-AuNPs (FHD: 31%; PLAL-AuNPs_S1: 46%; PLAL-AuNPs_S2: 50%), while the magnet-assisted transfection led to significantly lower efficiencies than the FHD protocol. With PLAL-AuNPs_S1 and _S2 the PI% was significantly higher, yet no consistent effect of these NPs on cell proliferation was observed. The magnet-assisted protocols were least effective, but did result in the lowest cytotoxic effect.Conclusions: This study demonstrated that transfection efficiency of DNA-expression-plasmids was significantly improved by the addition of AuNPs. In some combinations the respective cytotoxicity was increased depending on the type of the applied AuNPs and the transfected DNA construct. Consequently, our results indicate that for routine use of these AuNPs the specific nanoparticle formulation and DNA construct combination has to be considered. © 2011 Durán et al; licensee BioMed Central Ltd.
    view abstractdoi: 10.1186/1477-3155-9-47
  • 2011 • 118 Chemical and physical factors in design of antibiofouling polymer coatings
    Eshet, I. and Freger, V. and Kasher, R. and Herzberg, M. and Lei, J. and Ulbricht, M.
    Biomacromolecules 12 2681-2685 (2011)
    Because most "low fouling" polymers resisting bacterial attachment are hydrophilic, they are usually also significantly swollen. Swelling leads to purely physical dilution of interaction and weakens attachment; however, these nonspecific contributions are usually not separated from the specific effect of polymer chemistry. Taking advantage of the fact that chemistry and swelling of hydrogels may be independently varied through the fraction of a cross-linker, the roles of chemistry and physical dilution (swelling) in bacterial attachment are analyzed for selected hydrogels. Using as a quantitative indicator the rate of bacterial deposition in a parallel plate setup under defined flow conditions, the observed correlation of deposition rate with swelling provides a straightforward comparison of gels with different chemistries that can factor out the effect of swelling. In particular, it is found that chemistry appears to contribute similarly to bacterial deposition on hydrogels prepared from acrylamide and a zwitterioninic monomer 2-(methacryloyloxy)ethyl) dimethyl-(3-sulfopropyl) ammonium hydroxide so that the observed differences may be related to swelling only. In contrast, these gels were inferior to PEG-based hydrogels, even when swelling of the latter was lower, indicating a greater contribution of PEG chemistry to reduced bacterial deposition. This demonstrates that swelling must be accounted for when comparing different biofouling-resistant materials. Chemical and physical principles may be combined in hydrogel coatings to develop efficient antibiofouling surfaces. © 2011 American Chemical Society.
    view abstractdoi: 10.1021/bm200476g
  • 2011 • 117 Reduced protein adsorption by osmolytes
    Evers, F. and Steitz, R. and Tolan, M. and Czeslik, C.
    Langmuir 27 6995-7001 (2011)
    Osmolytes are substances that affect osmosis and are used by cells to adapt to environmental stress. Here, we report a neutron reflectivity study on the influence of some osmolytes on protein adsorption at solid-liquid interfaces. Bovine ribonuclease A (RNase) and bovine insulin were used as model proteins adsorbing at a hydrophilic silica and at a hydrophobic polystyrene surface. From the neutron reflectivity data, the adsorbed protein layers were characterized in terms of layer thickness, protein packing density, and adsorbed protein mass in the absence and presence of urea, trehalose, sucrose, and glycerol. All data point to the clear effect of these nonionic cosolvents on the degree of protein adsorption. For example, 1 M sucrose leads to a reduction of the adsorbed amount of RNase by 39% on a silica surface and by 71% on a polystyrene surface. Trehalose was found to exhibit activity similar to that of sucrose. The changes in adsorbed protein mass can be attributed to a decreased packing density of the proteins in the adsorbed layers. Moreover, we investigated insulin adsorption at a hydrophobic surface in the absence and presence of glycerol. The degree of insulin adsorption is decreased by even 80% in the presence of 4 M of glycerol. The results of this study demonstrate that nonionic cosolvents can be used to tune and control nonspecific protein adsorption at aqueous-solid interfaces, which might be relevant for biomedical applications. © 2011 American Chemical Society.
    view abstractdoi: 10.1021/la2010908
  • 2011 • 116 Ultrahigh-aspect ratio microfiber-furs as plant-surface mimics derived from teeth
    Fik, C.P. and Meuris, M. and Salz, U. and Bock, T. and Tiller, J.C.
    Advanced Materials 23 3565-3569 (2011)
    Ultrahydrophobic surfaces that mimic the surface of a Corokia cotoneaster leaf were created by using cow teeth as natural template. After UV curing of an acrylate resin and removing the template, a highly dense hairy fur-like structure with high aspect ratio could be obtained. Subsequent modification with silica nanoparticles and fluorosilane afforded a water contact angle of some 170°. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/adma.201101102
  • 2011 • 115 A facile synthesis of mesoporous crystalline tin oxide films involving a base-triggered formation of sol-gel building blocks
    Fried, D.I. and Ivanova, A. and Müller, V. and Rathousky, J. and Smarsly, B.M. and Fattakhova-Rohlfing, D.
    Nanoscale 3 1234-1239 (2011)
    We have developed a new facile procedure for manufacturing crystalline thin films of SnO2 with a uniform mesoporous architecture and full crystallinity of the walls. The procedure is based on the evaporation-induced self-assembly (EISA) of prehydrolyzed tin oxide precursor directed by a commercially available Pluronic polymer. The formation of the tin oxide precursor, which can be self-assembled into a mesoporous structure, is achieved by an addition of ammonium hydroxide to a tin tetrachloride solution. The relative concentration of ammonium hydroxide as well as the duration and temperature of the hydrolysis reaction influence significantly the properties of hydrolyzed tin oxide species and the mesostructure assembled from them. The films coated from these precursor solutions and calcined at 300 °C to 400 °C exhibit a well-developed worm-like porosity with a wall to wall distance of ca. 18 nm, a surface area of up to 50 cm2 cm-2 (corresponding to 55 ± 5 m2 g-1), and high crystallinity. © 2011 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c0nr00872a
  • 2011 • 114 F-doped Co3O4 photocatalysts for sustainable H 2 generation from water/ethanol
    Gasparotto, A. and Barreca, D. and Bekermann, D. and Devi, A. and Fischer, R.A. and Fornasiero, P. and Gombac, V. and Lebedev, O.I. and MacCato, C. and Montini, T. and Van Tendeloo, G. and Tondello, E.
    Journal of the American Chemical Society 133 19362-19365 (2011)
    p-Type Co3O4 nanostructured films are synthesized by a plasma-assisted process and tested in the photocatalytic production of H 2 from water/ethanol solutions under both near-UV and solar irradiation. It is demonstrated that the introduction of fluorine into p-type Co3O4 results in a remarkable performance improvement with respect to the corresponding undoped oxide, highlighting F-doped Co 3O4 films as highly promising systems for hydrogen generation. Notably, the obtained yields were among the best ever reported for similar semiconductor-based photocatalytic processes. © 2011 American Chemical Society.
    view abstractdoi: 10.1021/ja210078d
  • 2011 • 113 Real-space imaging of inelastic Friedel-like surface oscillations emerging from molecular adsorbates
    Gawronski, H. and Fransson, J. and Morgenstern, K.
    Nano Letters 11 2720-2724 (2011)
    We report real space imaging measurements of inelastic Friedel oscillations. The inelastic electron tunneling spectroscopy, using scanning tunneling microscopy, around dimers of dichlorobenze adsorbates on Au(111) surface display clear spatial modulations that we attribute to inelastic scattering at the molecular sites caused by molecular vibrations. Due to local interactions between the adsorbate and the surface states, the molecular vibrations generate a redistribution of the charge density at energies in a narrow range around the inelastic mode. Our experimental findings are supported by theoretical arguments. © 2011 American Chemical Society.
    view abstractdoi: 10.1021/nl201076g
  • 2011 • 112 Amplified detection of DNA hybridization using post-labelling with a biotin-modified intercalator
    Gbala, M. and Hartwich, G. and Schuhmann, W.
    Faraday Discussions 149 11-22 (2011)
    A 32-electrode microelectrode array modified with a self-assembled monolayer of a thiolated DNA capture strand and 11-mercapto-1-undecanol was used for the detection of multi-resistant Staphylococcus aureus (MRSA) upon hybridization of the complementary target DNA. In the proposed assay strategy the obtained double-stranded DNA (dsDNA) is at first non-covalently labeled by intercalation of a proflavine derivative which is functionalized via a flexible spacer with biotin moieties. Subsequent to this post-labelling a avidin/alkaline phosphatase conjugate is bound to the biotin moieties thus introducing a reporter group at sites bearing dsDNA. Hybridization and hence the presence of MRSA DNA is detected via oxidation of p-aminophenol enzymatically generated from p-aminophenylphosphate. The assay strategy was carefully evaluated using ferrocene-modified target strands. An increase in sensitivity of the proposed label-free DNA assays based on a careful design of the sensing interface and the implemented enzymatic amplification was achieved. © 2011 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c005365a
  • 2011 • 111 The influence of additions of Al and Si on the lattice stability of fcc and hcp Fe-Mn random alloys
    Gebhardt, T. and Music, D. and Ekholm, M. and Abrikosov, I.A. and Vitos, L. and Dick, A. and Hickel, T. and Neugebauer, J. and Schneider, J.M.
    Journal of Physics Condensed Matter 23 (2011)
    We have studied the influence of additions of Al and Si on the lattice stability of face-centred-cubic (fcc) versus hexagonal-closed-packed (hcp) Fe-Mn random alloys, considering the influence of magnetism below and above the fcc Néel temperature. Employing two different ab initio approaches with respect to basis sets and treatment of magnetic and chemical disorder, we are able to quantify the predictive power of the ab initio methods. We find that the addition of Al strongly stabilizes the fcc lattice independent of the regarded magnetic states. For Si a much stronger dependence on magnetism is observed. Compared to Al, almost no volume change is observed as Si is added to Fe-Mn, indicating that the electronic contributions are responsible for stabilization/destabilization of the fcc phase. © 2010 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0953-8984/23/24/246003
  • 2011 • 110 3D self-assembled plasmonic superstructures of gold nanospheres: Synthesis and characterization at the single-particle level
    Gellner, M. and Steinigeweg, D. and Ichilmann, S. and Salehi, M. and Schütz, M. and Kömpe, K. and Haase, M. and Schlücker, S.
    Small 7 3445-3451 (2011)
    The synthesis of 3D self-assembled plasmonic superstructures of gold nanospheres as well as the characterization of their structural and optical properties at the single-particle level is presented. This experimental work is complemented by FEM (finite element method) simulations of elastic scattering spectra and the spatial |E| 4 distribution for establishing structure-activity correlations in these complex 3D nanoclusters. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/smll.201102009
  • 2011 • 109 The influence of the potassium promoter on the kinetics and thermodynamics of CO adsorption on a bulk iron catalyst applied in Fischer-Tropsch synthesis: A quantitative adsorption calorimetry, temperature-programmed desorption, and surface hydrogenation study
    Graf, B. and Muhler, M.
    Physical Chemistry Chemical Physics 13 3701-3710 (2011)
    The adsorption of carbon monoxide on an either unpromoted or potassium-promoted bulk iron catalyst was investigated at 303 K and 613 K by means of pulse chemisorption, adsorption calorimetry, temperature-programmed desorption and temperature-programmed surface reaction in hydrogen. CO was found to adsorb mainly molecularly in the absence of H 2 at 303 K, whereas the presence of H 2 induced CO dissociation at higher temperatures leading to the formation of CH 4 and H 2O. The hydrogenation of atomic oxygen chemisorbed on metallic iron was found to occur faster than the hydrogenation of atomically adsorbed carbon. At 613 K CO adsorption occurred only dissociatively followed by recombinative CO 2 formation according to C ads + 2O ads → CO 2(g). The presence of the potassium promoter on the catalyst surface led to an increasing strength of the Fe-C bond both at 303 K and 613 K: the initial differential heat of molecular CO adsorption on the pure iron catalyst at 303 K amounted to 102 kJ mol -1, whereas it increased to 110 kJ mol -1 on the potassium-promoted sample, and the initial differential heat of dissociative CO adsorption on the unpromoted iron catalyst at 613 K amounted to 165 kJ mol -1, which increased to 225 kJ mol -1 in the presence of potassium. The calorimetric CO adsorption experiments also reveal a change of the energetic distribution of the CO adsorption sites present on the catalyst surface induced by the potassium promoter, which was found to block a fraction of the CO adsorption sites. © the Owner Societies 2011.
    view abstractdoi: 10.1039/c0cp01875a
  • 2011 • 108 Guanidiniocarbonyl-pyrrole-aryl conjugates as nucleic acid sensors: Switch of binding mode and spectroscopic responses by introducing additional binding sites into the linker
    Gröger, K. and Baretić, D. and Piantanida, I. and Marjanović, M. and Kralj, M. and Grabar, M. and Tomić, S. and Schmuck, C.
    Organic and Biomolecular Chemistry 9 198-209 (2011)
    Two novel guanidiniocarbonyl pyrrole-pyrene conjugates 3 and 4 as spectroscopic probes for ds-polynucleotides were synthesized and their interaction with different ds-DNAs/RNAs studied. Compared to a previously reported first set of conjugates (1 and 2) the significant extension and increased rigidity of the central part of the structure resulted in a switch of DNA binding mode from intercalative (previously studied derivatives 1 and 2 with a nonbinding and flexible linker) to minor groove binding of the two novel guanidiniocarbonyl-pyrrole-pyrene conjugates 3 and 4. These two compounds interact strongly with ds-DNAs, but only weakly with ds-RNA. The newly incorporated heterocyclic moieties within the central part of the structure of 3 and 4 were able to control by steric and hydrogen-bonding effects the alignment of the molecules within various, structurally different forms of DNA minor grooves, whereby even small differences in the position of the attached pyrene within the groove were reflected in different fluorimetric responses. In addition, 3 and 4 revealed intriguing in vitro selectivity among various human tumour cell lines. © 2011 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c0ob00103a
  • 2011 • 107 The collagen fibril architecture in the lamina cribrosa and peripapillary sclera predicted by a computational remodeling approach
    Grytz, R. and Meschke, G. and Jonas, J.B.
    Biomechanics and Modeling in Mechanobiology 10 371-382 (2011)
    The biomechanics of the optic nerve head is assumed to play an important role in ganglion cell loss in glaucoma. Organized collagen fibrils form complex networks that introduce strong anisotropic and nonlinear attributes into the constitutive response of the peripapillary sclera (PPS) and lamina cribrosa (LC) dominating the biomechanics of the optic nerve head. The recently presented computational remodeling approach (Grytz and Meschke in Biomech Model Mechanobiol 9:225-235, 2010) was used to predict the micro-architecture in the LC and PPS, and to investigate its impact on intraocular pressure-related deformations. The mechanical properties of the LC and PPS were derived from a microstructure-oriented constitutive model that included the stretch-dependent stiffening and the statistically distributed orientations of the collagen fibrils. Biomechanically induced adaptation of the local micro-architecture was captured by allowing collagen fibrils to be reoriented in response to the intraocular pressure-related loading conditions. In agreement with experimental observations, the remodeling algorithm predicted the existence of an annulus of fibrils around the scleral canal in the PPS, and a predominant radial orientation of fibrils in the periphery of the LC. The peripapillary annulus significantly reduced the intraocular pressure-related expansion of the scleral canal and shielded the LC from high tensile stresses. The radial oriented fibrils in the LC periphery reinforced the LC against transversal shear stresses and reduced LC bending deformations. The numerical approach presents a novel and reasonable biomechanical explanation of the spatial orientation of fibrillar collagen in the optic nerve head. © 2010 Springer-Verlag.
    view abstractdoi: 10.1007/s10237-010-0240-8
  • 2011 • 106 Identification of Eps15 as antigen recognized by the monoclonal antibodies aa2 and ab52 of the wuerzburg hybridoma library against Drosophila brain
    Halder, P. and Chen, Y.-c. and Brauckhoff, J. and Hofbauer, A. and Dabauvalle, M.-C. and Lewandrowski, U. and Winkler, C. and Sickmann, A. and Buchner, E.
    PLoS ONE 6 (2011)
    The Wuerzburg Hybridoma Library against the Drosophilabrain represents a collection of around 200 monoclonal antibodies that bind to specific structures in the Drosophila brain. Here we describe the immunohistochemical staining patterns, the Western blot signals of one- and two-dimensional electrophoretic separation, and the mass spectrometric characterization of the target protein candidates recognized by the monoclonal antibodies aa2 and ab52 from the library. Analysis of a mutant of a candidate gene identified the Drosophila homolog of the Epidermal growth factor receptor Pathway Substrate clone 15 (Eps15) as the antigen for these two antibodies. © 2011 Halder et al.
    view abstractdoi: 10.1371/journal.pone.0029352
  • 2011 • 105 Structurally designed synthesis of mechanically stable poly(benzoxazine-co- resol)-based porous carbon monoliths and their application as high-performance CO2 capture sorbents
    Hao, G.-P. and Li, W.-C. and Qian, D. and Wang, G.-H. and Zhang, W.-P. and Zhang, T. and Wang, A.-Q. and Schüth, F. and Bongard, H.-J. and Lu, A.-H.
    Journal of the American Chemical Society 133 11378-11388 (2011)
    Porous carbon monoliths with defined multilength scale pore structures, a nitrogen-containing framework, and high mechanical strength were synthesized through a self-assembly of poly(benzoxazine-co-resol) and a carbonization process. Importantly, this synthesis can be easily scaled up to prepare carbon monoliths with identical pore structures. By controlling the reaction conditions, porous carbon monoliths exhibit fully interconnected macroporosity and mesoporosity with cubic Im3m symmetry and can withstand a press pressure of up to 15.6 MPa. The use of amines in the synthesis results in a nitrogen-containing framework of the carbon monolith, as evidenced by the cross-polarization magic-angle-spinning NMR characterization. With such designed structures, the carbon monoliths show outstanding CO2 capture and separation capacities, high selectivity, and facile regeneration at room temperature. At 1 bar, the equilibrium capacities of the monoliths are in the range of 3.3 - 4.9 mmol g- 1 at 0 °C and of 2.6 - 3.3 mmol g - 1 at 25 °C, while the dynamic capacities are in the range of 2.7 - 4.1 wt % at 25 °C using 14% (v/v) CO2 in N2. The carbon monoliths exhibit high selectivity for the capture of CO2 over N2 from a CO2/N2 mixture, with a separation factor ranging from 13 to 28. Meanwhile, they undergo a facile CO2 release in an argon stream at 25 °C, indicating a good regeneration capacity. © 2011 American Chemical Society.
    view abstractdoi: 10.1021/ja203857g
  • 2011 • 104 Mechanistic studies of Fc-PNA(·DNA) surface dynamics based on the kinetics of electron-transfer processes
    Hüsken, N. and Gȩbala, M. and La Mantia, F. and Schuhmann, W. and Metzler-Nolte, N.
    Chemistry - A European Journal 17 9678-9690 (2011)
    N-Terminally ferrocenylated and C-terminally gold-surface-grafted peptide nucleic acid (PNA) strands were exploited as unique tools for the electrochemical investigation of the strand dynamics of short PNA(·DNA) duplexes. On the basis of the quantitative analysis of the kinetics and the diffusional characteristics of the electron-transfer process, a nanoscopic view of the Fc-PNA(·DNA) surface dynamics was obtained. Loosely packed, surface-confined Fc-PNA single strands were found to render the charge-transfer process of the tethered Fc moiety diffusion-limited, whereas surfaces modified with Fc-PNA·DNA duplexes exhibited a charge-transfer process with characteristics between the two extremes of diffusion and surface limitation. The interplay between the inherent strand elasticity and effects exerted by the electric field are supposed to dictate the probability of a sufficient approach of the Fc head group to the electrode surface, as reflected in the measured values of the electron-transfer rate constant, k 0. An in-depth understanding of the dynamics of surface-bound PNA and PNA·DNA strands is of utmost importance for the development of DNA biosensors using (Fc-)PNA recognition layers. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/chem.201003764
  • 2011 • 103 A density functional theory based estimation of the anharmonic contributions to the free energy of a polypeptide helix
    Ismer, L. and Ireta, J. and Neugebauer, J.
    Journal of Chemical Physics 135 (2011)
    We have employed density functional theory to determine the temperature dependence of the intrinsic stability of an infinite poly-L-alanine helix. The most relevant helix types, i.e., the - and the 310 - helix, and several unfolded conformations, which serve as reference for the stability analysis, have been included. For the calculation of the free energies for the various chain conformations we have explicitly included both, harmonic and anharmonic contributions. The latter have been calculated by means of a thermodynamic integration approach employing stochastic Langevin molecular dynamics, which is shown to provide a dramatic increase in the computational efficiency as compared to commonly employed deterministic molecular dynamics schemes. Employing this approach we demonstrate that the anharmonic part of the free energy amounts to the order of 0.1-0.4 kcal/mol per peptide unit for all analysed conformations. Although small, the anharmonic contribution stabilizes the helical conformations with respect to the fully extended structure. © 2011 American Institute of Physics.
    view abstractdoi: 10.1063/1.3629451
  • 2011 • 102 Stoichiometry of alloy nanoparticles from laser ablation of PtIr in acetone and their electrophoretic deposition on PtIr electrodes
    Jakobi, J. and Menéndez-Manjón, A. and Chakravadhanula, V.S.K. and Kienle, L. and Wagener, P. and Barcikowski, S.
    Nanotechnology 22 (2011)
    Charged Pt-Ir alloy nanoparticles are generated through femtosecond laser ablation of a Pt9Ir target in acetone without using chemical precursors or stabilizing agents. Preservation of the target's stoichiometry in the colloidal nanoparticles is confirmed by transmission electron microscopy (TEM)-energy-dispersive x-ray spectroscopy (EDX), high angle annular dark field (HAADF) scanning transmission electron microscopy (STEM)-EDX elemental maps, high resolution TEM and selected area electron diffraction (SAED) measurements. Results are discussed with reference to thermophysical properties and the phase diagram. The nanoparticles show a lognormal size distribution with a mean Feret particle size of 26nm. The zeta potential of - 45mV indicates high stability of the colloid with a hydrodynamic diameter of 63nm. The charge of the particles enables electrophoretic deposition of nanoparticles, creating nanoscale roughness on three-dimensional PtIr neural electrodes within a minute. In contrast to coating with Pt or Ir oxides, this method allows modification of the surface roughness without changing the chemical composition of PtIr. © 2011 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0957-4484/22/14/145601
  • 2011 • 101 Structure and phase behavior of archaeal lipid monolayers
    Jeworrek, C. and Evers, F. and Erlkamp, M. and Grobelny, S. and Tolan, M. and Chong, P.L.-G. and Winter, R.
    Langmuir 27 13113-13121 (2011)
    We report X-ray reflectivity (XRR) and grazing incidence X-ray diffraction (GIXD) measurements of archaeal bipolar tetraether lipid monolayers at the air-water interface. Specifically, Langmuir films made of the polar lipid fraction E (PLFE) isolated from the thermoacidophilic archaeon Sulfolobus acidocaldarius grown at three different temperatures, i.e., 68, 76, and 81 °C, were examined. The dependence of the structure and packing properties of PLFE monolayers on surface pressure were analyzed in a temperature range between 10 and 50 °C at different pH values. Additionally, the interaction of PLFE monolayers (using lipids derived from cells grown at 76 °C) with the ion channel peptide gramicidin was investigated as a function of surface pressure. A total monolayer thickness of approximately 30 Å was found for all monolayers, hinting at a U-shaped conformation of the molecules with both head groups in contact with the interface. The monolayer thickness increased with rising film pressure and decreased with increasing temperature. At 10 and 20 °C, large, highly crystalline domains were observed by GIXD, whereas at higher temperatures no distinct crystallinity could be observed. For lipids derived from cells grown at higher temperatures, a slightly more rigid structure in the lipid dibiphytanyl chains was observed. A change in the pH of the subphase had an influence only on the structure of the lipid head groups. The addition of gramicidin to an PLFE monolayer led to a more disordered state as observed by XRR. In GIXD measurements, no major changes in lateral organization could be observed, except for a decrease of the size of crystalline domains, indicating that gramicidin resides mainly in the disordered areas of the monolayer and causes local membrane perturbation, only. © 2011 American Chemical Society.
    view abstractdoi: 10.1021/la202027s
  • 2011 • 100 Effects of specific versus nonspecific ionic interactions on the structure and lateral organization of lipopolysaccharides
    Jeworrek, C. and Evers, F. and Howe, J. and Brandenburg, K. and Tolan, M. and Winter, R.
    Biophysical Journal 100 2169-2177 (2011)
    We report x-ray reflectivity and grazing incidence x-ray diffraction measurements of lipopolysaccharide (LPS) monolayers at the water-air interface. Our investigations reveal that the structure and lateral ordering of the LPS molecules is very different from phospholipid systems and can be modulated by the ionic strength of the aqueous subphase in an ion-dependent manner. Our findings also indicate differential effects of monovalent and divalent ions on the two-dimensional ordering of lipid domains. Na+ ions interact unspecifically with LPS molecules based on their ability to efficiently screen the negative charges of the LPS molecules, whereas Ca2+ ions interact specifically by cross-linking adjacent molecules in the monolayer. At low lateral pressures, Na+ ions present in the subphase lead to a LPS monolayer structure ordered over large areas with high compressibility, nearly hexagonal packing of the hydrocarbon chains, and high density in the LPS headgroup region. At higher film pressures, the LPS monolayer becomes more rigid and results in a less perfect, oblique packing of the LPS hydrocarbon chains as well as a smaller lateral size of highly ordered domains on the monolayer. Furthermore, associated with the increased surface pressure, a conformational change of the sugar headgroups occurs, leading to a thickening of the entire LPS monolayer structure. The effect of Ca2+ ions in the subphase is to increase the rigidity of the LPS monolayer, leading to an oblique packing of the hydrocarbon chains already at low film pressures, an upright orientation of the sugar moieties, and much smaller sizes of ordered domains in the plane of the monolayer. In the presence of both Na+-and Ca2+ ions in the subphase, the screening effect of Na+ is predominant at low film pressures, whereas, at higher film pressures, the structure and lateral organization of LPS molecules is governed by the influence of Ca2+ ions. The unspecific charge-screening effect of the Na+ ions on the conformation of the sugar moiety becomes less dominant at biologically relevant lateral pressures. © 2011 by the Biophysical Society.
    view abstractdoi: 10.1016/j.bpj.2011.03.019
  • 2011 • 99 Colloidal metal nanoparticles as a component of designed catalyst
    Jia, C.-J. and Schüth, F.
    Physical Chemistry Chemical Physics 13 2457-2487 (2011)
    Recent advances in the synthesis of collidal metal nanoparticles of controlled sizes and shapes that are relevant for catalyst design are reviewed. Three main methods, based on colloid chemistry techniques in solution, i.e., chemical reduction of metal salt precursors, electrochemical synthesis, and controlled decomposition of organometallic compounds and metal-surfactant complexes, are used to synthesize metal nanoparticles. Their catalytic activity and selectivity depend on the shape, size and composition of the metal nanoparticles, and the support effect, as shown for many reactions in quasi-homogeneous and heterogeneous catalysis. A specially designed type of thermally stable catalysts - "embedded" metal catalysts, in which metal nanoparticles are isolated by porous support shells so that metal sintering is effectively avoided at high temperatures, are also introduced. The ultilization of pre-prepared colloidal metal nanoparticles with tuned size, shape and composition as components of designed catalysts opens up new field in catalysis. © 2011 the Owner Societies.
    view abstractdoi: 10.1039/c0cp02680h
  • 2011 • 98 Polythiophene-assisted vapor phase synthesis of carbon nanotube-supported rhodium sulfide as oxygen reduction catalyst for HCl electrolysis
    Jin, C. and Nagaiah, T.C. and Xia, W. and Bron, M. and Schuhmann, W. and Muhler, M.
    ChemSusChem 4 927-930 (2011)
    Rhodium Drive: Carbon nanotube-supported rhodium sulfide electrocatalysts are prepared by sequential chemical vapor deposition of iron, controlled vapor phase polymerization of thiophene, and finally impregnation of the rhodium precursor and pyrolysis. The electrocatalysts are applied in the oxygen reduction reaction under HCl electrolysis conditions. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.201000315
  • 2011 • 97 A minimalist model for ion partitioning and competition in a K + channel selectivity filter
    Kast, S.M. and Kloss, T. and Tayefeh, S. and Thiel, G.
    Journal of General Physiology 138 371-373 (2011)
    doi: 10.1085/jgp.201110694
  • 2011 • 96 Superheated rubber for cold storage
    Katzenberg, F. and Heuwers, B. and Tiller, J.C.
    Advanced Materials 23 1909-1911 (2011)
    Highly stretched rubber cools down upon relaxation. A natural rubber material that stores high elongations up to 1000% strain upon strain-induced crystallization at room temperature is reported. The strain recovered and, with this, the stored "cold" is released only by a thermal or athermal trigger. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/adma.201100408
  • 2011 • 95 Element-specific magnetic hysteresis of individual 18 nm Fe nanocubes
    Kronast, F. and Friedenberger, N. and Ollefs, K. and Gliga, S. and Tati-Bismaths, L. and Thies, R. and Ney, A. and Weber, R. and Hassel, C. and Römer, F.M. and Trunova, A.V. and Wirtz, C. and Hertel, R. and Dürr, H.A. and Farle, M.
    Nano Letters 11 1710-1715 (2011)
    Correlating the electronic structure and magnetic response with the morphology and crystal structure of the same single ferromagnetic nanoparticle has been up to now an unresolved challenge. Here, we present measurements of the element-specific electronic structure and magnetic response as a function of magnetic field amplitude and orientation for chemically synthesized single Fe nanocubes with 18 nm edge length. Magnetic states and interactions of monomers, dimers, and trimers are analyzed by X-ray photoemission electron microscopy for different particle arrangements. The element-specific electronic structure can be probed and correlated with the changes of magnetic properties. This approach opens new possibilities for a deeper understanding of the collective response of magnetic nanohybrids in multifunctional materials and in nanomagnetic colloidal suspensions used in biomedical and engineering technologies. © 2011 American Chemical Society.
    view abstractdoi: 10.1021/nl200242c
  • 2011 • 94 Nucleotide recognition in water by a guanidinium-based artificial tweezer receptor
    Kuchelmeister, H.Y. and Schmuck, C.
    Chemistry - A European Journal 17 5311-5318 (2011)
    The water-soluble tweezer receptor 1 with two symmetric peptidic arms, which are connected by an aromatic scaffold and contain lysine, phenylalanine, and a guanidinium-based anion-binding site as headgroup, has been synthesized. UV/Vis-derived Job plots show that the receptor forms 1:1 complexes with nucleotides and phosphate in buffered water at neutral pH. Binding constants have been determined by fluorescence and UV/Vis spectroscopy. All nucleotides tested were bound very efficiently, even in pure water, with binding constants between 104 and 105 M-1. Interestingly, all mononucleotides were bound much stronger than phosphate by a factor of at least 5 to 10. Furthermore 1 favors the binding of adenosine monophosphate (AMP) over adenosine diphosphate (ADP) and adenosine triphosphate (ATP), which is unprecedented for artificial nucleotide receptors reported so far. According to NMR spectroscopy and molecular modeling studies, the efficient binding is a result of strong electrostatic contacts supported by π-π interactions with the nucleobase within the cavity-shaped receptor. Nucleotides preferred: The symmetric peptide-based tweezer receptor 1 forms stable 1:1 complexes with nucleotides in water (pH 7). The host prefers nucleotides over phosphate and mononucleotides over di- or trinucleotides (see scheme). Hence, complex formation is due also to π-stacking interactions with the nucleobase. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/chem.201003393
  • 2011 • 93 Diluting the hydrogen bonds in viscous solutions of n-butanol with n-bromobutane: II. A comparison of rotational and translational motions
    Lederle, C. and Hiller, W. and Gainaru, C. and Böhmer, R.
    Journal of Chemical Physics 134 (2011)
    Mixtures of the monohydroxy alcohol n-butanol with n-bromobutane are investigated via dielectric and nuclear magnetic resonance (NMR) techniques. Static- and pulsed-field gradient proton NMR yielded self-diffusion coefficients as a function of concentration and temperature. To monitor reorientational motions, broadband dielectric and 13C-spin relaxation time measurements were carried out. The latter demonstrate that the structural relaxation stems from the motion of the alkyl chains. By combining data from translational diffusion coefficients with published shear viscosities, hydrodynamic radii were determined that compare favorably with the van der Waals radii of single molecules. The results for the neat alcohol and for the binary mixtures are discussed with respect to a recent transient chain model. The approach of Debye and structural relaxation times at high temperatures, identified as a general feature of monohydroxy alcohols, is also discussed within that framework. © 2011 American Institute of Physics.
    view abstractdoi: 10.1063/1.3549123
  • 2011 • 92 Mechanical properties of liquid-filled shellac composite capsules
    Leick, S. and Kott, M. and Degen, P. and Henning, S. and Päsler, T. and Suter, D. and Rehage, H.
    Physical Chemistry Chemical Physics 13 2765-2773 (2011)
    This paper describes the mechanical properties of thin-walled, liquid-filled composite capsules consisting of calcium pectinate and shellac. In a series of experiments we measured the deformation of these particles in a spinning drop apparatus. For different pH-values we studied the elastic properties of these particles and compared the obtained results with the mechanical response measured by squeezing capsule experiments. In analogy to these experiments, we also investigated liquid-filled unloaded calcium pectinate capsules without the addition of shellac. The deformation properties of these experiments and the surface Young moduli were in good agreement. Furthermore we investigated the liquid-filled calcium pectinate and the composite capsules by NMR microscopy. These experiments allowed investigations of the membrane thickness and the kinetics of membrane growing. Additional characterizations by stress controlled small amplitude surface shear experiments of similar composed gel layers provided coherent results for the surface Young modulus. © 2011 the Owner Societies.
    view abstractdoi: 10.1039/c0cp01803a
  • 2011 • 91 Structural analysis of articular cartilage using multiphoton microscopy: Input for biomechanical modeling
    Lilledahl, M.B. and Pierce, D.M. and Ricken, T. and Holzapfel, G.A. and Davies, C.D.L.
    IEEE Transactions on Medical Imaging 30 1635-1648 (2011)
    The 3-D morphology of chicken articular cartilage was quantified using multiphoton microscopy (MPM) for use in continuum-mechanical modeling. To motivate this morphological study we propose aspects of a new, 3-D finite strain constitutive model for articular cartilage focusing on the essential load-bearing morphology: an inhomogeneous, poro-(visco)elastic solid matrix reinforced by an anisotropic, (visco)elastic dispersed fiber fabric which is saturated by an incompressible fluid residing in strain-dependent pores. Samples of fresh chicken cartilage were sectioned in three orthogonal planes and imaged using MPM, specifically imaging the collagen fibers using second harmonic generation. Employing image analysis techniques based on Fourier analysis, we derived the principal directionality and dispersion of the collagen fiber fabric in the superficial layer. In the middle layer, objective thresholding techniques were used to extract the volume fraction occupied by extracellular collagen matrix. In conjunction with information available in the literature, or additional experimental testing, we show how this data can be used to derive a 3-D map of the initial solid volume fraction and Darcy permeability. © 2011 IEEE.
    view abstractdoi: 10.1109/TMI.2011.2139222
  • 2011 • 90 Strong cation exchange chromatography for analysis of sialylated glycopeptides
    Lohrig, K. and Sickmann, A. and Lewandrowski, U.
    Methods in Molecular Biology 753 299-308 (2011)
    Glycosylations represent major and essential co- and post-translational modification forms of proteins and facilitate a multitude of functions such as cell-cell interactions as well as protein folding and stability. The analysis of protein glycosylation is still an enormous task due to the vast heterogeneity and multi-tude of different possible carbohydrate structures. The elucidation of glycosylation sites - the attachment points of carbohydrate structures to the polypeptide backbone - is often among the first necessary steps of analysis. Therefore, we here present a simple protocol for charge-based enrichment of sialylated glycopeptides by strong cation exchange chromatography and subsequent analysis of glycosylation sites by mass spectrometry. © Springer Science+Business Media, LLC 2011.
    view abstractdoi: 10.1007/978-1-61779-148-2_20
  • 2011 • 89 Accumulation of silver nanoparticles by cultured primary brain astrocytes
    Luther, E.M. and Koehler, Y. and Diendorf, J. and Epple, M. and Dringen, R.
    Nanotechnology 22 (2011)
    Silver nanoparticles (AgNP) are components of various food industry products and are frequently used for medical equipment and materials. Although such particles enter the vertebrate brain, little is known on their biocompatibility for brain cells. To study the consequences of an AgNP exposure of brain cells we have treated astrocyte-rich primary cultures with polyvinylpyrrolidone (PVP)-coated AgNP. The incubation of cultured astrocytes with micromolar concentrations of AgNP for up to 24h resulted in a time-and concentration-dependent accumulation of silver, but did not compromise the cell viability nor lower the cellular glutathione content. In contrast, the incubation of astrocytes for 4h with identical amounts of silver as AgNO 3 already severely compromised the cell viability and completely deprived the cells of glutathione. The accumulation of AgNP by astrocytes was proportional to the concentration of AgNP applied and significantly lowered by about 30% in the presence of the endocytosis inhibitors chloroquine or amiloride. Incubation at 4 °C reduced the accumulation of AgNP by 80% compared to the values obtained for cells that had been exposed to AgNP at 37 °C. These data demonstrate that viable cultured brain astrocytes efficiently accumulate PVP-coated AgNP in a temperature-dependent process that most likely involves endocytotic pathways. © 2011 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0957-4484/22/37/375101
  • 2011 • 88 Dissolution of iron oxide nanoparticles inside polymer nanocapsules
    Möller, J. and Cebi, M. and Schroer, M.A. and Paulus, M. and Degen, P. and Sahle, C.J. and Wieland, D.C.F. and Leick, S. and Nyrow, A. and Rehage, H. and Tolan, M.
    Physical Chemistry Chemical Physics 13 20354-20360 (2011)
    The structure of poly(organosiloxane) nanocapsules partially filled with iron oxide cores of different sizes was revealed by small angle X-ray scattering and X-ray diffraction. The nanocapsules are synthesized by the formation of a poly(organosiloxane) shell around iron oxide nanoparticles and the simultaneous partial dissolution of these cores. Due to the high scattering contrast of the iron oxide cores compared to the polymer shell, the particle size distribution of the cores inside the capsules can be measured by small angle X-ray scattering. Additional information can be revealed by X-ray diffraction, which gives insights into the formation of the polymer network and the structure of the iron oxide cores. The study shows how the crystallinity and size of the nanoparticles as well as the shape and width of the size distribution can be altered by the synthesis parameters. © 2011 the Owner Societies.
    view abstractdoi: 10.1039/c1cp22161b
  • 2011 • 87 Structure and flow of droplets on solid surfaces
    Müller-Buschbaum, P. and Magerl, D. and Hengstler, R. and Moulin, J.-F. and Körstgens, V. and Diethert, A. and Perlich, J. and Roth, S.V. and Burghammer, M. and Riekel, C. and Gross, M. and Varnik, F. and Uhlmann, P. and Stamm, ...
    Journal of Physics Condensed Matter 23 (2011)
    The structure and flow of droplets on solid surfaces is investigated with imaging and scattering techniques and compared to simulations. To access nanostructures at the liquid-solid interface advanced scattering techniques such as grazing incidence small-angle x-ray scattering (GISAXS) with micro-and nanometer-sized beams, GISAXS and insitu imaging ellipsometry and GISAXS tomography are used. Using gold nanoparticle suspensions, structures observed in the wetting area due to deposition are probed insitu during the drying of the droplets. After drying, nanostructures in the wetting area and inside the dried droplets are monitored. In addition to drying, a macroscopic movement of droplets is caused by body forces acting on an inclined substrate. The complexity of the solid surfaces is increased from simple silicon substrates to binary polymer brushes, which undergo a switching due to the liquid in the droplet. Nanostructures introduced in the polymer brush due to the movement of droplets are observed. © 2011 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0953-8984/23/18/184111
  • 2011 • 86 Phosphoproteome analysis of the platelet plasma membrane
    Premsler, T. and Lewandrowski, U. and Sickmann, A. and Zahedi, R.P.
    Methods in Molecular Biology 728 279-290 (2011)
    Blood platelets are key players standing at the crossroads between physiologically occurring hemostasis and pathologic thrombus formation. As these cellular particles lack a nucleus, intra- and intercellular processes involved in platelet activity and function are almost exclusively regulated on the protein level. In particular, posttranslational protein modification by phosphorylation, which allows for a quick and highly dynamic transduction of cellular signals, is discussed in this context. In addition, since platelet activation and aggregation usually require surface contact with the surrounding tissue, special interest focuses on this contacting region, and hence on the subproteome of the platelet plasma membrane. In this chapter, we present a mass spectrometry-driven approach capable of dealing with the task of platelet plasma membrane proteomics and phosphoproteomics. The outlined protocols include strategies for the isolation and purification of plasma membrane proteins by aqueous two-phase partitioning and subsequent enrichment of phosphopeptides via titanium dioxide chromatography. © 2011 Springer Science+Business Media, LLC.
    view abstractdoi: 10.1007/978-1-61779-068-3_19
  • 2011 • 85 Nanostructuring of titania thin films by a combination of microfluidics and block-copolymer-based sol-gel templating
    Rawolle, M. and Ruderer, M.A. and Prams, S.M. and Zhong, Q. and Magerl, D. and Perlich, J. and Roth, S.V. and Lellig, P. and Gutmann, J.S. and Müller-Buschbaum, P.
    Small 7 884-891 (2011)
    Sol-gel templating of titania thin films with the amphiphilic diblock copolymer poly(dimethyl siloxane)-block-methyl methacrylate poly(ethylene oxide) is combined with microfluidic technology to control the structure formation. Due to the laminar flow conditions in the microfluidic cell, a better control of the local composition of the reactive fluid is achieved. The resulting titania films exhibit mesopores and macropores, as determined with scanning electron microscopy, X-ray reflectivity, and grazing incidence small angle X-ray scattering. The titania morphology has three features that are beneficial for application in photovoltaics: 1) a large surface-to-volume ratio important for charge generation with disordered hexagonally arranged mesopores of 25 nm size and a film porosity of up to 0.79, 2) enhanced light scattering that enables the absorption of more light, and 3) a dense titania layer with a thickness of about 6 nm at the substrate (bottom electrode) to prevent short circuits. An optical characterization complements the structural investigation. Microfluidics and sol-gel templating are combined to design titania thin films with well defined structures. The obtained films consist of mesopores with a diameter of 25 nm and macropores, as seen with scanning electron microscopy and grazing incidence small angle X-ray scattering. This structure is interesting for potential applications in inorganic-organic photovoltaics because of the large surface area and enhanced light scattering as compared to structures templated without microfluidics. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/smll.201001734
  • 2011 • 84 Janus cylinders at liquid-liquid interfaces
    Ruhland, T.M. and Gröschel, A.H. and Walther, A. and Müller, A.H.E.
    Langmuir 27 9807-9814 (2011)
    We describe the first study on the self-assembly behavior of Janus cylinders at liquid/liquid interfaces. The Janus cylinders are characterized by a phase separation along the major axis into two hemicylinders of different wettability. The pendant drop technique and microscopic imaging were used to characterize the adsorption behavior and self-assembly of Janus cylinders at perfluorinated oil/dioxane and perfluorinated oil/dimethyl sulfoxide interfaces. According to the evolution of the interfacial tension and a series of TEM images taken during the cylinder adsorption, we will specify the characteristics of early to late stages of the Janus cylinder adsorption at a liquid-liquid interface and discuss the effect of Janus cylinder length and their concentration. We also establish that the broken symmetry of the corona leads to significantly higher interfacial activity as compared to homogeneous core-shell cylinders. The adsorption is characterized by three different adsorption stages: first, free diffusion to the interface, followed by continuous adsorption of cylinders including ordering and domain formation and, finally, additional packing with a rearrangement of domains and formation of a loose multilayer system. © 2011 American Chemical Society.
    view abstractdoi: 10.1021/la201863x
  • 2011 • 83 Covalent tethering of protruding arms for addressable DNA nanostructures
    Saccà, B. and Niemeyer, C.M.
    Small 7 2887-2898 (2011)
    Functionalization of self-assembled DNA nanostructures is of fundamental importance for the realization of their application in nanotechnology and biosensing. Approaches reported so far suffer from lack of general applicability and usually require careful system design to avoid poor yields in the assembly of target structures. A novel approach well suited for fabrication of addressable DNA superstructures is reported here to generate DNA tile motifs. The method is based on the covalent linkage of a single-stranded protruding arm (covPA) to one of the oligomers forming the tile. Subsequent to assembly of tile motifs and superlattices, the covPA can be addressed by hybridization with complementary oligonucleotides or DNA-protein conjugates. The covPA can be located at arbitrary positions in a given tile motif without changing the general design and without compromising the structural integrity of the tile. The covPA strategy can also be readily extended to different PA sequences and multiple covPA arms can be linked to a tile. Superlattices obtained by self-assembly of covPA tiles reveal partial folding into double layers which possess an intrinsic order at the ultrastructural level. This phenomenon is likely associated with the increased flexibility of the covPA and might open up novel ways for DNA-based functionalization of solid surfaces and other applications of structural DNA nanotechnology. A novel class of DNA tile motifs bears a covalently linked, single-stranded protruding arm. The increased flexibility of this arm enables efficient modification of tiles and superlattices with complementary DNA-linked objects and induces formation of partially folded bilayers which posses an intrinsic order at the ultrastructural level. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/smll.201101010
  • 2011 • 82 Liquid-crystalline elastomer microvalve for microfluidics
    Sánchez-Ferrer, A. and Fischl, T. and Stubenrauch, M. and Albrecht, A. and Wurmus, H. and Hoffmann, M. and Finkelmann, H.
    Advanced Materials 23 4526-4530 (2011)
    Microactuators are an essential component in microsystems or microdevices, and in applications that include artificial muscles, pumps, valves, or switchers. Liquid-crystalline elastomers are a new class of actuator material in the field of microsystem technologies, which can be used in standard processes. This newly developed actuator provides new possibilities in microfluidics because of its dimensional changes activated by the increase in temperature. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/adma.201102277
  • 2011 • 81 Electronic excitations induced by hydrogen surface chemical reactions on gold
    Schindler, B. and Diesing, D. and Hasselbrink, E.
    Journal of Chemical Physics 134 (2011)
    Associated with chemical reactions at surfaces energy may be dissipated exciting surface electronic degrees of freedom. These excitations are detected using metal-insulator-metal (MIM) heterostructures (Ta-TaOx-Au) and the reactions of H with and on a Au surface are probed. A current corresponding to 510-5 electrons per adsorbing H atom and a marked isotope effect are observed under steady-state conditions. Analysis of the current trace when the H atom flux is intermitted suggests that predominantly the recombination reaction creates electronic excitations. Biasing the front versus the back electrode of the MIM structure provides insights into the spectrum of electronic excitations. The observed spectra differ for the two isotopes H and D and are asymmetric when comparing negative and positive bias voltages. Modeling indicates that the excited electrons and the concurrently created holes differ in their energy distributions. © 2011 American Institute of Physics.
    view abstractdoi: 10.1063/1.3523647
  • 2011 • 80 Immuno-surface-enhanced coherent anti-Stokes Raman scattering microscopy: Immunohistochemistry with target-specific metallic nanoprobes and nonlinear Raman microscopy
    Schlücker, S. and Salehi, M. and Bergner, G. and Schütz, M. and Ströbel, P. and Marx, A. and Petersen, I. and Dietzek, B. and Popp, J.
    Analytical Chemistry 83 7081-7085 (2011)
    Immunohistochemistry (IHC) is one of the most widely used staining techniques for diagnostic purposes. The selective localization of target proteins in tissue specimens by conventional IHC is achieved with dye- or enzyme-labeled antibodies in combination with light microscopy. In this contribution, we demonstrate the proof-of-principle for IHC based on surface-enhanced coherent Raman scattering for contrast generation. Specifically, antibody-labeled metallic nanoshells in conjunction with surface-enhanced coherent anti-Stokes Raman scattering (SECARS) microscopy are employed for the selective, sensitive, and rapid localization of the basal cell protein p63 in normal prostate tissue. Negative control experiments were performed in order to confirm the selective binding of the target-specific metal nanoprobes and to disentangle the role of plasmonic (metal) and molecular (Raman reporter) resonances in this plasmon-assisted four-wave mixing technique. © 2011 American Chemical Society.
    view abstractdoi: 10.1021/ac201284d
  • 2011 • 79 Exploring the piezophilic behavior of natural cosolvent mixtures
    Schroer, M.A. and Zhai, Y. and Wieland, D.C.F. and Sahle, C.J. and Nase, J. and Paulus, M. and Tolan, M. and Winter, R.
    Angewandte Chemie - International Edition 50 11413-11416 (2011)
    Marine organisms have evolved a surprising mechanism to counteract the deleterious effects of urea by trimethylammonium N-oxide (TMAO). The effect of pressure on the structure and intermolecular interactions of lysozyme in urea and TMAO solutions was studied (see picture). These findings help to understand the compensatory effect of urea-TMAO mixtures in deep-sea organisms. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201104380
  • 2011 • 78 Wetting morphologies and their transitions in grooved substrates
    Seemann, R. and Brinkmann, M. and Herminghaus, S. and Khare, K. and Law, B.M. and McBride, S. and Kostourou, K. and Gurevich, E. and Bommer, S. and Herrmann, C. and Michler, D.
    Journal of Physics Condensed Matter 23 (2011)
    When exposed to a partially wetting liquid, many natural and artificial surfaces equipped with complex topographies display a rich variety of liquid interfacial morphologies. In the present article, we focus on a few simple paradigmatic surface topographies and elaborate on the statics and dynamics of the resulting wetting morphologies. It is demonstrated that the spectrum of wetting morphologies increases with increasing complexity of the groove structure. On elastically deformable substrates, additional structures in the liquid morphologies can be observed, which are caused by deformations of the groove geometry in the presence of capillary forces. The emergence of certain liquid morphologies in grooves can be actively controlled by changes in wettability and geometry. For electrically conducting solid substrates, the apparent contact angle can be varied by electrowetting. This allows, depending on groove geometry, a reversible or irreversible transport of liquid along surface grooves. In the case of irreversible liquid transport in triangular grooves, the dynamics of the emerging instability is sensitive to the apparent hydrodynamic slip at the substrate. On elastic substrates, the geometry can be varied in a straightforward manner by stretching or relaxing the sample. The imbibition velocity in deformable grooves is significantly reduced compared to solid grooves, which is a result of the microscopic deformation of the elastic groove material close to the three phase contact line. © 2011 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0953-8984/23/18/184108
  • 2011 • 77 Experimental and theoretical studies of the colloidal stability of nanoparticles?a general interpretation based on stability maps
    Segets, D. and Marczak, R. and Schäfer, S. and Paula, C. and Gnichwitz, J.-F. and Hirsch, A. and Peukert, W.
    ACS Nano 5 4658-4669 (2011)
    The current work addresses the understanding of the stabilization of nanoparticles in suspension. Specifically, we study ZnO in ethanol for which the influence of particle size and reactant ratio as well as surface coverage on colloidal stability in dependence of the purification progress was investigated. The results revealed that the well-known 〈-potential determines not only the colloidal stability but also the surface coverage of acetate groups bound to the particle surface. The acetate groups act as molecular spacers between the nanoparticles and prevent agglomeration. Next to DLVO calculations based on the theory of Derjaguin, Landau, Verwey and Overbeek using a core-shell model we find that the stability is better understood in terms of dimensionless numbers which represent attractive forces as well as electrostatic repulsion, steric effects, transport properties, and particle concentration. Evaluating the colloidal stability in dependence of time by means of UV-vis absorption measurements a stability map for ZnO is derived. From this map it becomes clear that the dimensionless steric contribution to colloidal stability scales with a stability parameter including dimensionless repulsion and attraction as well as particle concentration and diffusivity of the particles according to a power law with an exponent of ?0.5. Finally, we show that our approach is valid for other stabilizing molecules like cationic dendrons and is generally applicable for a wide range of other material systems within the limitations of vanishing van der Waals forces in refractive index matched situations, vanishing 〈-potential and systems without a stabilizing shell around the particle surface. © 2011 American Chemical Society.
    view abstractdoi: 10.1021/nn200465b
  • 2011 • 76 Electron transfer between genetically modified Hansenula polymorpha yeast cells and electrode surfaces via os-complex modified redox polymers
    Shkil, H. and Schulte, A. and Guschin, D.A. and Schuhmann, W.
    ChemPhysChem 12 806-813 (2011)
    Graphite electrodes modified with redox-polymer-entrapped yeast cells were investigated with respect to possible electron-transfer pathways between cytosolic redox enzymes and the electrode surface. Either wild-type or genetically modified Hansenula polymorpha yeast cells over-expressing flavocytochrome b2 (FC b2) were integrated into Os-complex modified electrodeposition polymers. Upon increasing the L-lactate concentration, an increase in the current was only detected in the case of the genetically modified cells. The overexpression of FC b2 and the related amplification of the FC b2/L-lactate reaction cycle was found to be necessary to provide sufficient charge to the electron-exchange network in order to facilitate sufficient electrochemical coupling between the cells, via the redox polymer, to the electrode. The close contact of the Os-complex modified polymer to the cell wall appeared to be a prerequisite for electrically wiring the cytosolic FC b2/L-lactate redox activity and suggests the critical involvement of a plasma membrane redox system. Insights in the functioning of whole-cell-based bioelectrochemical systems have to be considered for the successful design of whole-cell biosensors or microbial biofuel cells. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cphc.201000889
  • 2011 • 75 Synthetic pathways to make nanoparticles fluorescent
    Sokolova, V. and Epple, M.
    Nanoscale 3 1957-1962 (2011)
    In biosciences, it is often necessary to follow the pathway of nanoparticles within cells or tissues. The nanoparticles can be used as labeled sensors which may, e.g., address functionalities within a cell, carry other specific agents like drugs or be magnetic for tumor thermotherapy. In the context of nanotoxicology, the fate of a given nanoparticle is of interest. As many methods in cell biology are based on fluorescence detection, there is a strong demand to make nanoparticles fluorescent. Different ways to introduce fluorescence are reviewed and exemplified with typical kinds of nanoparticles, i.e. polymers, silica and calcium phosphate. © 2011 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c1nr00002k
  • 2011 • 74 Fast and cost-effective purification of gold nanoparticles in the 20-250 nm size range by continuous density gradient centrifugation
    Steinigeweg, D. and Schütz, M. and Salehi, M. and Schlücker, S.
    Small 7 2443-2448 (2011)
    A multilayer quasi-continuous density gradient centrifugation method for separating 20-250 nm metal colloids with high size resolution while maintaining particle stability is presented. Colloidal mixtures containing monodisperse gold nanospheres and clusters thereof, in particular, gold dimers, are purified with yields up to 94%. The rapid method uses standard laboratory equipment. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/smll.201100663
  • 2011 • 73 800mg Darunavir tablets prepared by hot melt extrusion
    Thommes, M. and Baert, L. and Rosier, J.
    Pharmaceutical Development and Technology 16 645-650 (2011)
    Darunavir (TMC 114) is a protease inhibitor used in the therapy of HIV-1. The aim of this study was to formulate 800mg of Darunavir in a single unit dosage form, with suitable mechanical properties and dissolution behavior, using a corotating twin screw extruder. In preliminary investigations, extrudates of 1mm diameter were prepared to evaluate the extrusion and dissolution behavior of Darunavir. Two different poloxamers (188 and 407) were used to modify the dissolution properties of Darunavir, and a higher solubilization for poloxamer 188 was observed. Furthermore, a zero order drug release from pure Darunavir extrudates was found which was modulated by the extrudate diameter. Extrudates of 13mm diameter were cut into tablets containing 800mg of Darunavir. Due to the lower specific surface area in comparison to the 1mm extrudates, an addition of solubilizing agent was required to obtain the desired dissolution profiles. Therefore, the influence of Mannitol and poloxamer 188 was investigated in different formulations. The formulations exhibited acceptable extrusion behavior and dissolution properties. © 2011 Informa Healthcare USA, Inc.
    view abstractdoi: 10.3109/10837450.2010.508077
  • 2011 • 72 Microfluidic emulsion separation - Simultaneous separation and sensing by multilayer nanofilm structures
    Uhlmann, P. and Varnik, F. and Truman, P. and Zikos, G. and Moulin, J.-F. and Müller-Buschbaum, P. and Stamm, M.
    Journal of Physics Condensed Matter 23 (2011)
    Emulsion separation is of high relevance for filtration applications, liquid-liquid-partitioning of biomolecules like proteins and recovery of products from droplet microreactors. Selective interaction of various components of an emulsion with substrates is used to design microfluidic flow chambers for efficient separation of emulsions into their individual components. Our lab-on-a-chip device consists of an emulsion separation cell with an integrated silicon sensor chip, the latter allowing the detection of liquid motion via the field-effect signal. Thus, within our lab-on-a-chip device, emulsions can be separated while the separation process is monitored simultaneously. For emulsion separation a surface energy step gradient, namely a sharp interface between the hydrophobic and hydrophilic parts of the separation chamber, is used. The key component of the lab-on-a-chip system is a multilayer and multifunctional nanofilm structure which not only provides the surface energy step gradient for emulsion separation but also constitutes the functional parts of the field-effect transistors. The proof-of-principle was performed using a model emulsion consisting of immiscible aqueous and organic solvent components. Droplet coalescence was identified as a key aspect influencing the separation process, with quite different effects during separation on open surfaces as compared to slit geometry. For a detailed description of this observation, an analytical model was derived and lattice Boltzmann computer simulations were performed. By use of grazing incidence small angle x-ray scattering (GISAXS) interfacial nanostructures during gold nanoparticle deposition in a flow field were probed to demonstrate the potential of GISAXS for insitu investigations during flow. © 2011 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0953-8984/23/18/184123
  • 2011 • 71 Stability and dynamics of droplets on patterned substrates: Insights from experiments and lattice Boltzmann simulations
    Varnik, F. and Gross, M. and Moradi, N. and Zikos, G. and Uhlmann, P. and Müller-Buschbaum, P. and Magerl, D. and Raabe, D. and Steinbach, I. and Stamm, M.
    Journal of Physics Condensed Matter 23 (2011)
    The stability and dynamics of droplets on solid substrates are studied both theoretically and via experiments. Focusing on our recent achievements within the DFG-priority program 1164 (Nano-and Microfluidics), we first consider the case of (large) droplets on the so-called gradient substrates. Here the term gradient refers to both a change of wettability (chemical gradient) or topography (roughness gradient). While the motion of a droplet on a perfectly flat substrate upon the action of a chemical gradient appears to be a natural consequence of the considered situation, we show that the behavior of a droplet on a gradient of topography is less obvious. Nevertheless, if care is taken in the choice of the topographic patterns (in order to reduce hysteresis effects), a motion may be observed. Interestingly, in this case, simple scaling arguments adequately account for the dependence of the droplet velocity on the roughness gradient (Moradi et al 2010 Europhys. Lett. 8926006). Another issue addressed in this paper is the behavior of droplets on hydrophobic substrates with a periodic arrangement of square shaped pillars. Here, it is possible to propose an analytically solvable model for the case where the droplet size becomes comparable to the roughness scale (Gross et al 2009 Europhys. Lett. 8826002). Two important predictions of the model are highlighted here. (i)There exists a state with a finite penetration depth, distinct from the full wetting (Wenzel) and suspended (Cassie-Baxter, CB) states. (ii)Upon quasi-static evaporation, a droplet initially on the top of the pillars (CB state) undergoes a transition to this new state with a finite penetration depth but then (upon further evaporation) climbs up the pillars and goes back to the CB state again. These predictions are confirmed via independent numerical simulations. Moreover, we also address the fundamental issue of the internal droplet dynamics and the terminal center of mass velocity on a flat substrate. © 2011 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0953-8984/23/18/184112
  • 2011 • 70 Impact of in situ polymer coating on particle dispersion into solid laser-generated nanocomposites
    Wagener, P. and Brandes, G. and Schwenke, A. and Barcikowski, S.
    Physical Chemistry Chemical Physics 13 5120-5126 (2011)
    The crucial step in the production of solid nanocomposites is the uniform embedding of nanoparticles into the polymer matrix, since the colloidal properties or specific physical properties are very sensitive to particle dispersion within the nanocomposite. Therefore, we studied a laser-based generation method of a nanocomposite which enables us to control the agglomeration of nanoparticles and to increase the single particle dispersion within polyurethane. For this purpose, we ablated targets of silver and copper inside a polymer-doped solution of tetrahydrofuran by a picosecond laser (using a pulse energy of 125 μJ at 33.3 kHz repetition rate) and hardened the resulting colloids into solid polymers. Electron microscopy of these nanocomposites revealed that primary particle size, agglomerate size and particle dispersion strongly depend on concentration of the polyurethane added before laser ablation. 0.3 wt% polyurethane is the optimal polymer concentration to produce nanocomposites with improved particle dispersion and adequate productivity. Lower polyurethane concentration results in agglomeration whereas higher concentration reduces the production rate significantly. The following evaporation step did not change the distribution of the nanocomposite inside the polyurethane matrix. Hence, the in situ coating of nanoparticles with polyurethane during laser ablation enables simple integration into the structural analogue polymer matrix without additives. Furthermore, it was possible to injection mold these in situ-stabilized nanocomposites without affecting particle dispersion. This clarifies that sufficient in situ stabilization during laser ablation in polymer solution is able to prevent agglomeration even in a hot polymer melt. © the Owner Societies 2011.
    view abstractdoi: 10.1039/c0cp02262d
  • 2011 • 69 Pitfalls in the characterization of nanoporous and nanosized materials
    Weidenthaler, C.
    Nanoscale 3 792-810 (2011)
    With the advent of highly sophisticated analytical tools, numerous physical methods are nowadays available for comprehensive characterization of inorganic matter and, as special cases, of porous and nanosized materials. Intelligent experimental setup and correct evaluation of the experimental data can provide helpful insights into the chemical and physical properties of such materials. However, scanning of literature reports shows that in many cases evaluation and interpretation of experimental data are erroneous. As a result, the description of a new material can be useless or even worse, misleading. Wrong evaluation is even more critical if mechanistic theories are based on such data. Characterization of porous and/or nanosized materials is mainly performed by gas adsorption, X-ray powder diffraction, electron microscopy and surface spectroscopy. For correct interpretation of experimental data one should be aware of certain pitfalls. The present paper summarizes prominent faults and may show how they can be avoided. It is supposed to provide some hand-on knowledge on correct analysis of materials. Addressed are primarily non-experts and researchers being new to the field of characterization of inorganic nanosized or nanoporous materials. © 2011 The Royal Society of Chemistry.
    view abstractdoi: 10.1039/c0nr00561d
  • 2010 • 68 In situ studies on the switching behavior of ultrathin poly(acrylic acid) polyelectrolyte brushes in different aqueous environments
    Aulich, D. and Hoy, O. and Luzinov, I. and Brücher, M. and Hergenröder, R. and Bittrich, E. and Eichhorn, K.-J. and Uhlmann, P. and Stamm, M. and Esser, N. and Hinrichs, K.
    Langmuir 26 12926-12932 (2010)
    The pH-dependent switching of a poly(acrylic acid) (PAA) polyelectrolyte brush was investigated in situ using infrared spectroscopic ellipsometry (IRSE). The brush was synthesized by a "grafting to" procedure on silicon substrate with a native oxide layer. The overall thickness of the PAA brush in the dry state was ∼5 nm. Reversible switching of the polymer brush was studied at titration from pH 2 to 10 and back in steps of 1 pH unit. The switching process was observed by monitoring the characteristic vibrational bands of the carboxylic groups of the PAA molecules. Decreasing of the C=O vibrational band amplitude and arising of a COO- vibrational band proved the chemical changes in the molecular structure of the brushes due to changes of the pH value in the aqueous solution. Due to the strong absorption of these bands in the IR region, the switching process could be monitored clearly. Switching the brush in several cycles with increasing and decreasing pH value showed a hysteresis-like behavior. For the first time, such hysteresis is observed in titration experiments of polyelectrolyte brushes. This behavior is attributed to the complex mechanisms of the ions mobility in the brush layer which is explained with a suggested simplifying model describing the influence of ions inside the brush layer. In addition to the IRSE measurements, X-ray standing waves (XSW), in situ visible ellipsometry, and contact angle measurements have been performed and were in good agreement with the results from IRSE. Repetition of the in situ measurement cycles proved the good reversibility of the switching process which is highly important for practical applications of polymer brushes. © 2010 American Chemical Society.
    view abstractdoi: 10.1021/la101762f
  • 2010 • 67 A microelectrochemical sensing system for the determination of Epstein-Barr virus antibodies
    Bandilla, M. and Zimdars, A. and Neugebauer, S. and Motz, M. and Schuhmann, W. and Hartwich, G.
    Analytical and Bioanalytical Chemistry 398 2617-2623 (2010)
    An electrochemical method for the detection of Epstein-Barr virus (EBV) infections is described. The method relies on an immunoassay with electrochemical read-outs based on recombinant antigens. The antigens are immobilised on an Au electrode surface and used to complementarily bind antibodies from serum samples found during different stages of infection with EBV. Thiol chemistry under formation of self-assembled monolayers functions as a means to immobilise the antigens at the Au electrodes. A reporter system consisting of a secondary antibody labelled with alkaline phosphatase is used for electrochemical detection. The feasibility of the assay design is demonstrated and the assay performance is tested against the current gold standard in EBV detection. Close correlation is obtained for the results found for the developed electrochemical immunoassay and a standard line assay. Moreover, the electrochemical immunoassay is combined with a nanoporous electrode system allowing signal amplification by means of redox recycling. An amplification factor of 24 could be achieved. © Springer-Verlag 2010.
    view abstractdoi: 10.1007/s00216-010-3926-y
  • 2010 • 66 Perfluorocarbon-filled poly(lactide-co-gylcolide) nano- and microcapsules as artificial oxygen carriers for blood substitutes: A physico-chemical assessment
    Bauer, J. and Zähres, M. and Zellermann, A. and Kirsch, M. and Petrat, F. and De Groot, H. and Mayer, C.
    Journal of Microencapsulation 27 122-132 (2010)
    The physico-chemical suitability of perfluorocarbon-filled capsules as artificial oxygen carriers for blood substitutes is assessed on the example of biodegradable poly(lactide-co-gylcolide) micro- and nanocapsules with a liquid content of perfluorodecalin. The morphology of the capsules is studied by confocal laser scanning microscopy using Nile red as a fluorescent marker. The mechanical stability and the wall flexibility of the capsules are examined by atomic force microscopy. The permeability of the capsule walls in connection with the oxygen uptake is detected by nuclear magnetic resonance. It is shown that the preparation in fact leads to nanocapsules with a mechanical stability which compares well with the one of red blood cells. The capsule walls exhibit sufficient permeability to allow for the exchange of oxygen in aqueous environment. In the fully saturated state, the amount of oxygen dissolved within the encapsulated perfluorodecalin in aqueous dispersion is as large as for bulk perfluorodecalin. Simple kinetic studies are presently restricted to the time scale of minutes, but so far indicate that the permeability of the capsule walls could be sufficient to allow for rapid gas exchange.
    view abstractdoi: 10.3109/02652040903052002
  • 2010 • 65 Artificial single variant martensite in freestanding Fe70Pd 30 films obtained by coherent epitaxial growth
    Bechtold, C. and Buschbeck, J. and Lotnyk, A. and Erkartal, B. and Hamann, S. and Zamponi, C. and Schultz, L. and Ludwig, Al. and Kienle, L. and Fähler, S. and Quandt, E.
    Advanced Materials 22 2668-2671 (2010)
    (Figure Presented) The mechanically soft behavior of the magnetic shape-memory material Fe70Pd30 allows huge tetragonal distortions to be stabilized in sputtered thin films by coherent epitaxial growth on various metallic buffers. Furthermore, it is demonstrated that epitaxial films more than 1 μm thick can be grown, which makes possible freestanding films in an artificial single variant state suitable for microactuators and sensors. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA.
    view abstractdoi: 10.1002/adma.201000599
  • 2010 • 64 An efficient nickel catalyst for the reduction of carbon dioxide with a borane
    Chakraborty, S. and Zhang, J. and Krause, J.A. and Guan, H.
    Journal of the American Chemical Society 132 8872-8873 (2010)
    Nickel hydride with a diphosphinite-based ligand catalyzes the highly efficient reduction of CO2 with catecholborane, and the hydrolysis of the resulting methoxyboryl species produces CH3OH in good yield. The mechanism involves a nickel formate, formaldehyde, and a nickel methoxide as different reduced stages for CO2. The reaction may also be catalyzed by an air-stable nickel formate. © 2010 American Chemical Society.
    view abstractdoi: 10.1021/ja103982t
  • 2010 • 63 Optical properties of a nanomatch-like plasmonic structure
    Cui, X. and Zhang, W. and Erni, D. and Dong, L.
    Journal of the Optical Society of America A: Optics and Image Science, and Vision 27 1783-1790 (2010)
    The optical properties of a match-like plasmonic nanostructure are numerically investigated using full-wave finite-difference time-domain analysis in conjunction with dispersive material models. This work is mainly motivated by the developed technique enabling reproducible fabrication of nanomatch structures as well as the growing applications that utilize the localized field enhancement in plasmonic nanostructures. Our research revealed that due to the pronounced field enhancement and larger resonance tunabilities, some nanomatch topologies show potentials for various applications in the field of, e.g., sensing as well as a novel scheme for highly reproducible tips in scanning near field optical microscopy, among others. Despite the additional degrees of freedom that are offered by the composite nature of the proposed nanomatch topology, the paper also reflects on a fundamental complication intrinsic to the material interfaces especially in the nanoscale: stoichiometric mixing. We conclude that the specificity in material modeling will become a significant issue in future research on functionalized composite nanostructures. © 2010 Optical Society of America.
    view abstractdoi: 10.1364/JOSAA.27.001783
  • 2010 • 62 The resorption of nanocrystalline calcium phosphates by osteoclast-like cells
    Detsch, R. and Hagmeyer, D. and Neumann, M. and Schaefer, S. and Vortkamp, A. and Wuelling, M. and Ziegler, G. and Epple, M.
    Acta Biomaterialia 6 3223-3233 (2010)
    Nanocrystalline calcium phosphates containing carbonate have a high similarity to bone mineral. The reactions of bone cells (primary osteoblasts and osteoclast-like cells) on these materials as well as on sintered β-tricalcium phosphate and hydroxyapatite (HA) confirmed a good biocompatibility of the nanocrystalline samples. However, osteoclastic differentiation was constrained on the carbonate-rich samples, leading to a small number of osteoclast-like cells on the materials and few resorption pits. The grain size of the calcium phosphate ceramics (nano vs. micro) was less important than expected from to physico-chemical considerations. When comparing the nanocrystalline samples, the highest resorption rate was found for nano-HA with a low carbonate content, which strongly stimulated the differentiation of osteoclast-like cells on its surface. © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
    view abstractdoi: 10.1016/j.actbio.2010.03.003
  • 2010 • 61 Characterization of a novel interaction between vasodilator-stimulated phosphoprotein and abelson interactor 1 in human platelets: A concerted computational and experimental approach
    Dittrich, M. and Strassberger, V. and Fackler, M. and Tas, P. and Lewandrowski, U. and Sickmann, A. and Walter, U. and Dandekar, T. and Birschmann, I.
    Arteriosclerosis, Thrombosis, and Vascular Biology 30 843-850 (2010)
    Objective: The goal of this study was systematic profiling of vasodilator-stimulated phosphoprotein (VASP)-Ena/VASP homology 1 (EVH1) interactors in human platelets using a combined in silico and in vitro approach. Methods and results: Exploiting the information of the comprehensive proteome catalogue in the PlateletWeb database (http://plateletweb.bioapps.biozentrum. uni-wuerzburg.de/PlateletWeb.php), we performed a motif search of all sequences and identified potential target sites of class I EVH1 domains in human platelet proteins. Performing affinity purification with VASP-EVH1 domain and the lysates of platelets, we examined complex partners by mass spectrometry. Combining the results of both analyses, we identified Abelson interactor 1 (Abi-1) as a novel EVH1 domain-specific interaction partner of VASP in human platelets and investigated this interaction by yeast 2-hybrid mutational studies and immunoprecipitation. Immunofluorescence microscopy indicated colocalization of both proteins at the lamellipodia of spread human platelets, suggesting a role in reorganizing the cytoskeleton during spreading. Conclusion: The combination of experimental and computational interactome research has emerged as a valuable tool for the analysis of protein-protein interaction networks and facilitates the discovery and characterization of novel interactions as detailed here for Abi-1 and VASP in human platelets. System biological approaches can be expected to play an important role in basic and clinical platelet research, as they offer the potential to analyze signal transduction beyond the scope of established pathways. © 2010 American Heart Association, Inc.
    view abstractdoi: 10.1161/ATVBAHA.109.200683
  • 2010 • 60 Probing adsorption and aggregation of insulin at a poly(acrylic acid) brush
    Evers, F. and Reichhart, C. and Steitz, R. and Tolan, M. and Czeslik, C.
    Physical Chemistry Chemical Physics 12 4375-4382 (2010)
    A planar poly(acrylic acid) (PAA) brush provides an unusual substrate for the unspecific immobilization of proteins on material surfaces. At neutral pH-values, proteins adsorb at a PAA brush when the ionic strength of the protein solution is low. In contrast, raising the ionic strength to a few 100 mM transforms a PAA brush into a rather protein-resistant surface coating. Moreover, a PAA brush represents a mild environment for adsorbed proteins which preserves their secondary structure and biological activity. In this study, we focus on the biocompatibility of a PAA brush with an insulin solution. Insulin can form amyloid fibrils, which may also be triggered by interfaces. Using neutron reflectometry and attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, the effects of pD value, ionic strength, and glycerol concentration on the density profile and the secondary structure of adsorbed insulin molecules at a PAA brush have been studied. At pD 7, insulin adsorbs at a PAA brush despite its negative net charge. As has been found for other proteins in earlier studies, increasing the ionic strength of the insulin solution to 500 mM decreases the amount of adsorbed insulin drastically. In contrast, at pD 2, addition of salt to the insulin solution induces a thick insulin adsorbate at a PAA brush suggesting both protein-brush and protein-protein interactions, i.e., insulin adsorption and aggregation to be effective. However, in the presence of 2 M glycerol, insulin adsorption is largely suppressed. Furthermore, no major alterations of the secondary structure of adsorbed insulin can be detected by ATR-FTIR spectroscopy under all conditions studied. Hence, the performed experiments demonstrate that a PAA brush does not promote the formation of insulin amyloid structures, which represents a fundamentally new aspect of the biocompatibility of this material surface coating. © 2010 the Owner Societies.
    view abstractdoi: 10.1039/b925134k
  • 2010 • 59 Adaptation and focusing of optode configurations for fluorescence optical tomography by experimental design methods
    Freiberger, M. and Clason, C. and Scharfetter, H.
    Journal of Biomedical Optics 15 (2010)
    Fluorescence tomography excites a fluorophore inside a sample by light sources on the surface. From boundary measurements of the fluorescent light, the distribution of the fluorophore is reconstructed. The optode placement determines the quality of the reconstructions in terms of, e.g., resolution and contrast-to-noise ratio. We address the adaptation of the measurement setup. The redundancy of the measurements is chosen as a quality criterion for the optodes and is computed from the Jacobian of the mathematical formulation of light propagation. The algorithm finds a subset with minimum redundancy in the measurements from a feasible pool of optodes. This allows biasing the design in order to favor reconstruction results inside a given region. Two different variations of the algorithm, based on geometric and arithmetic averaging, are compared. Both deliver similar optode configurations. The arithmetic averaging is slightly more stable, whereas the geometric averaging approach shows a better conditioning of the sensitivity matrix and mathematically corresponds more closely with entropy optimization. Adapted illumination and detector patterns are presented for an initial set of 96 optodes placed on a cylinder with focusing on different regions. Examples for the attenuation of fluorophore signals from regions outside the focus are given. © 2010 Society of Photo-Optical Instrumentation Engineers.
    view abstractdoi: 10.1117/1.3316405
  • 2010 • 58 Controlled orientation of DNA in a binary SAM as a key for the successful determination of DNA hybridization by means of electrochemical impedance spectroscopy
    Gebala, M. and Schuhmann, W.
    ChemPhysChem 11 2887-2895 (2010)
    Determination of DNA hybridization at electrode surfaces modified with thiol-tethered single-stranded DNA (ssDNA) capture probes and co-assembled with short-chain thiol derivatives using electrochemical impedance spectroscopy requires a careful design of the electrode/electrolyte interface as well as an in-depth understanding of the processes at the interface during DNA hybridization. The influence of the electrode potential, the ssDNA coverage, the ionic strength, the nature of the thiol derivative and especially the Debye length are shown to have a significant impact on the impedance spectra. A mixed monolayer comprising-in addition to the ssDNA capture probe-both mercaptohexanol (MCH) and mercaptopropionic acid (MPA) is suggested as an interface design which allows a high efficiency of the DNA hybridization concomitantly with a reliable modulation of the charge-transfer resistance of the electrode upon hybridization. © 2010 Wiley-VCH Verlag GmbH& Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cphc.201000210
  • 2010 • 57 Measurement and control of in-plane surface chemistry during the oxidation of H-terminated (111) Si
    Gökce, B. and Adles, E.J. and Aspnes, D.E. and Gundogdu, K.
    Proceedings of the National Academy of Sciences of the United States of America 107 17503-17508 (2010)
    In-plane directional control of surface chemistry during interface formation can lead to new opportunities regarding device structures and applications. Control of this type requires techniques that can probe and hence provide feedback on the chemical reactivity of bonds not only in specific directions but also in real time. Here, we demonstrate both control and measurement of the oxidation of H-terminated (111) Si. Control is achieved by externally applying uniaxial strain, and measurement by second-harmonic generation (SHG) together with the anisotropic-bond model of nonlinear optics. In this system anisotropy results because bonds in the strain direction oxidize faster than those perpendicular to it, leading in addition to transient structural changes that can also be detected at the bond level by SHG.
    view abstractdoi: 10.1073/pnas.1011295107
  • 2010 • 56 An aqueous emulsion route to synthesize mesoporous carbon vesicles and their nanocomposites
    Gu, D. and Bongard, H. and Deng, Y. and Feng, D. and Wu, Z. and Fang, Y. and Mao, J. and Tu, B. and Schüth, F. and Zhao, D.
    Advanced Materials 22 833-837 (2010)
    Onionlike mesoporous carbon and carbonsilica nanocomposites with multilayer vesicle structures can be synthesized by an organic-inorganic co-assembly method under hydrothermal conditions in an aqueous emulsion solution (see figure). The nanocomposite vesicles have ordered lamellar mesostructures with about 3-9 layers and carbon pillars are located between the neighboring shells. (Chemical Equation Persentation). © 2010 WILEY-VCH Verlag GmbH & Co. KGaA.
    view abstractdoi: 10.1002/adma.200902550
  • 2010 • 55 Redox electrodeposition polymers: Adaptation of the redox potential of polymer-bound Os complexes for bioanalytical applications
    Guschin, D.A. and Castillo, J. and Dimcheva, N. and Schuhmann, W.
    Analytical and Bioanalytical Chemistry 398 1661-1673 (2010)
    The design of polymers carrying suitable ligands for coordinating Os complexes in ligand exchange reactions against labile chloro ligands is a strategy for the synthesis of redox polymers with bound Os centers which exhibit a wide variation in their redox potential. This strategy is applied to polymers with an additional variation of the properties of the polymer backbone with respect to pH-dependent solubility, monomer composition, hydrophilicity etc. A library of Os-complex-modified electrodeposition polymers was synthesized and initially tested with respect to their electron-transfer ability in combination with enzymes such as glucose oxidase, cellobiose dehydrogenase, and PQQ-dependent glucose dehydrogenase entrapped during the pH-induced deposition process. The different polymer-bound Os complexes in a library containing 50 different redox polymers allowed the statistical evaluation of the impact of an individual ligand to the overall redox potential of an Os complex. Using a simple linear regression algorithm prediction of the redox potential of Os complexes becomes feasible. Thus, a redox polymer can now be designed to optimally interact in electron-transfer reactions with a selected enzyme. © 2010 Springer-Verlag.
    view abstractdoi: 10.1007/s00216-010-3982-3
  • 2010 • 54 Flexibility and Sorption Selectivity in Rigid Metal-Organic Frameworks: The Impact of Ether-Functionalised Linkers
    Henke, S. and Schmid, R. and Grunwaldt, J. D. and Fischer, R. A.
    Chemistry-a European Journal 16 14296--14306 (2010)
    The functionalisation of well-known rigid metal organic frameworks (namely, [Zn4O(bdc)(3)](n), MOF-5, IRMOF-1 and [Zn-2(bdc)(2)(dabco)](n); bdc = 1,4-benzene dicarboxylate, dabco=diazabicyclo[2.2.2]octane) with additional alkyl ether groups of the type -O-(CH2)(n)-O-CH3 (n = 2-4) initiates unexpected structural flexibility, as well as high sorption selectivity towards CO2 over N-2 and CH, in the porous materials. These novel materials respond to the presence/absence of guest molecules with structural transformations. We found that the chain length of the alkyl ether groups and the substitution pattern of the bdc-type linker have a major impact on structural flexibility and sorption selectivity. Remarkably, our results show that a high crystalline order of the activated material is not a prerequisite to achieve significant porosity and high sorption selectivity.
    view abstractdoi: 10.1002/chem.201002341
  • 2010 • 53 Proapoptotic influenza A virus protein PB1-F2 forms a nonselective ion channel
    Henkel, M. and Mitzner, D. and Henklein, P. and Meyer-Almes, F.-J. and Moroni, A. and DiFrancesco, M.L. and Henkes, L.M. and Kreim, M. and Kast, S.M. and Schubert, U. and Thiel, G.
    PLoS ONE 5 (2010)
    Background: PB1-F2 is a proapoptotic influenza A virus protein of approximately 90 amino acids in length that is located in the nucleus, cytosol and in the mitochondria membrane of infected cells. Previous studies indicated that the molecule destabilizes planar lipid bilayers and has a strong inherent tendency for multimerization. This may be correlate with its capacity to induce mitochondrial membrane depolarization. Methodology/Principal Findings: Here, we investigated whether PB1-F2 is able to form ion channels within planar lipid bilayers and microsomes. For that purpose, a set of biologically active synthetic versions of PB1-F2 (sPB1-F2) derived from the IAV isolates A/Puerto Rico/8/34(H1N1) (IAVPR8), from A/Brevig Mission/1/1918(H1N1) (IAVSF2) or the H5N1 consensus sequence (IAVBF2) were used. Electrical and fluorimetric measurements show that all three peptides generate in planar lipid bilayers or in liposomes, respectively, a barely selective conductance that is associated with stochastic channel type fluctuations between a closed state and at least two defined open states. Unitary channel fluctuations were also generated when a truncated protein comprising only the 37 c-terminal amino acids of sPB1-F2 was reconstituted in bilayers. Experiments were complemented by extensive molecular dynamics simulations of the truncated fragment in a lipid bilayer. The results indicate that the c-terminal region exhibits a slightly bent helical fold, which is stable and remains embedded in the bilayer for over 180 ns. Conclusion/Significance: The data support the idea that PB1-F2 is able to form protein channel pores with no appreciable selectivity in membranes and that the c-terminus is important for this function. This information could be important for drug development. © 2010 Henkel et al.
    view abstractdoi: 10.1371/journal.pone.0011112
  • 2010 • 52 Guanidiniocarbonylpyrrole-aryl derivatives: Structure tuning for spectrophotometry; recognition of specific DNA and RNA sequences and for antiproliferative activity
    Hernandez-Folgado, L. and Baretić, D. and Piantanida, I. and Marjanović, M. and Kralj, M. and Rehm, T. and Schmuck, C.
    Chemistry - A European Journal 16 3036-3056 (2010)
    We present a systematic study of different guanidiniocarbonylpyrrole-aryl derivatives designed to interact with DNA or RNA both through intercalation of an aromatic moiety into the base stack of the nucleotide and through groove binding of a guanidiniocarbonylpyrrole cation. We varied 1 ) the size of the aromatic ring (benzene, naphthalene, pyrene and acridine), 2) the length and flexibility of the linker connecting the two binding groups, and 3) the total number of positive charges present at different pH values. The compounds and their interactions with DNA and RNA were studied by UV/Vis, fluorescence and CD spectroscopy. Antiproliferative activities against human tumour cell lines were also determined. Our studies show that efficient interaction with, for example, DNA requires a significantly large aromatic ring (pyrene) connected through a flexible linker to the pyrrole moiety. However, a positive charge, as in 12, is also needed. Compound 12 allows for base-pair-selective recognition of ds-DNA at physiological pH values. The antiproliferative activities of these compounds correlate with their binding affinities towards DNA, suggesting that their biological effects are most probably due to DNA binding. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.
    view abstractdoi: 10.1002/chem.200901999
  • 2010 • 51 Salt bridges in the miniature viral channel Kcv are important for function
    Hertel, B. and Tayefeh, S. and Kloss, T. and Hewing, J. and Gebhardt, M. and Baumeister, D. and Moroni, A. and Thiel, G. and Kast, S.M.
    European Biophysics Journal 39 1057-1068 (2010)
    The viral potassium channel Kcv comprises only 94 amino acids, which represent the pore module of more complex K+channels. As for Kir-type channels, Kcv also has a short N-terminal helix exposed to the cytoplasm, upstream of the Wrst transmembrane domain. Here we show that this helix is relevant for Kcv function. The presence of charged amino acids, which form dynamic inter- and intrasubunit salt bridges is crucial. Electrophysiological measurements, yeast rescue experiments and molecular dynamics simulations show that mutants in which the critical salt bridge formation is impaired have no or reduced channel activity. We conclude that these salt bridges destabilise the complexation of K+ions by negative charges on the inner transmembrane domain at the entrance into the cavity. This feature facilitates a continuous and coordinated transfer of ions between the cavity and the cytoplasm for channels without the canonical bundle crossing. © European Biophysical Societies' Association 2009.
    view abstractdoi: 10.1007/s00249-009-0451-z
  • 2010 • 50 Effect of urea and glycerol on the adsorption of ribonuclease a at the air-water interface
    Hüsecken, A.K. and Evers, F. and Czeslik, C. and Tolan, M.
    Langmuir 26 13429-13435 (2010)
    This study reports on the influence of nonionic cosolvents on the interfacial structure of ribonuclease A (RNase) adsorbed at the air-water interface. We applied X-ray reflectometry to obtain detailed volume fraction profiles of the adsorbed layers and to follow the effect of glycerol and urea on the adsorbate structure as a function of cosolvent concentration. Under all conditions studied, the adsorbed RNase layer maintains its compact shape, and the adsorbed RNase molecules adopt a flat-on orientation at the interface. Both kosmotropic glycerol and chaotropic urea exert profound effects on the adsorbate: The surface excess decreases linearly with glycerol content and is also reduced at low urea concentration. However, at high urea concentration, parts of the adsorbed layer are dehydrated and become exposed to air. The electron density and volume fraction profiles of the adsorbed protein provide clear evidence that these effects are ruled by different mechanisms. © 2010 American Chemical Society.
    view abstractdoi: 10.1021/la102222z
  • 2010 • 49 Shearforce-based constant-distance scanning electrochemical microscopy as fabrication tool for needle-type carbon-fiber nanoelectrodes
    Hussien, E.M. and Schuhmann, W. and Schulte, A.
    Analytical Chemistry 82 5900-5905 (2010)
    Carbon fiber nanoelectrodes with nanometer radii tip curvatures were fabricated using a shearforce-based constant-distance scanning electrochemical microscope and electrochemically induced polymer deposition. A simple DC etching procedure in alkaline solution provided conically sharpened single carbon fibers with well-formed nanocones at their bottom. Coating the stems but not the end of the tips of the tapered structures with anodic electrodeposition paint was the strategy for limiting the bare carbon to the foremost end and restricting a feasible voltammetry current response to exactly this section. The electrodeposition of the polymer was prevented at the foremost end of the tip using a shearforce-based tip-to-sample distance control that allowed approaching the etched tips carefully in just touching distance to a film of a silicone elastomer. Analysis of the steady-state cyclic voltammograms in presence of a reversible redox compound revealed effective radii for the obtained needle-type carbon-fiber nanoelectrodes down to as small as 46 nm. The method offers an alternative pathway toward the fabrication of highly miniaturized carbon electrodes. © 2010 American Chemical Society.
    view abstractdoi: 10.1021/ac100738b
  • 2010 • 48 Magnetic alloy nanoparticles from laser ablation in cyclopentanone and their embedding into a photoresist
    Jakobi, J. and Petersen, S. and Menéndez-Manjón, A. and Wagener, P. and Barcikowski, S.
    Langmuir 26 6892-6897 (2010)
    The generation of nonoxidized magnetic alloy nanoparticles is still a challenge using conventional chemical reduction methods. However, because these nanoparticles are currently attracting much attention, alternative methods are required. In this context, the applicability of femtosecond laser ablation, which has evolved as a powerful tool for the generation of colloidal metal nanoparticles, has been investigated using the example of Ni48Fe 52 and Sm2Co17 ablation in cyclopentanone. Besides stability and size measurements, the focus has been placed on the analysis of the elemental composition of nanoparticles, which proved the preservation of the stoichiometry of the target in Ni-Fe nanoparticles but not in Sm-Co. It is assumed that this is due to a greater difference in the heat of evaporation of the bulk alloy components in Sm-Co than in Ni-Fe. Hence, the successful generation of magnetic alloy nanoparticles is possible for alloys composed of elements with similar heats of evaporation. This one-step approach allows the fabrication of nanomagnetic polymer composites (e.g., with application prospects in microtechnology such as microactuators). © 2010 American Chemical Society.
    view abstractdoi: 10.1021/la101014g
  • 2010 • 47 Intramolecular electronic interactions between nonconjugated arene and quinone chromophores
    Jansen, G. and Kahlert, B. and Klärner, F.-G. and Boese, R. and Bläser, D.
    Journal of the American Chemical Society 132 8581-8592 (2010)
    The novel surprisingly colorful dark blue and orange-red molecular clips 1 and 2 containing a central p-benzoquinone spacer-unit and anthracene or napththalene sidewalls were synthesized by DDQ oxidation of the corresponding colorless hydroquinone clips 7 and 8. The colors of the quinone clips result from broad absorption bands in the visible range (1, λ<inf>max</inf> = 537 nm and 2, λ<inf>max</inf> = 423 and λ<inf>shoulder</inf> =515 nm) showing bathochromic shifts of 112 and 90 nm, respectively, compared to the similarly tetraalkyl-substituted duroquinone 31, even though the clips 1 and 2 only contain insulated π systems as chromophores, a central tetraalkyl-substituted p-benzoquinone spacer-unit and two anthracene or two naphthalene sidewalls. To elucidate the electronic properties of these clips, we prepared the compound 3, the anti-configured isomer of clip 2, and the benzene-, naphthalene-, and anthracene-substituted quinones 4, 5, and 6, the so-called "half-clips". The "half-clips" 6 and 5 show a similar color change and the same trend in the UV/vis absorption spectra as the anthracene and naphthalene clip 1 and 2. This finding already rules out that the color of these systems is a result of "through-space" π-π interactions between the aromatic sidewalls in the molecular clips 1 and 2. Quantum chemical ab initio calculations provide good evidence that the bathochromic shift of the absorption band at the longest wavelength observed in the UV/vis spectra of the clip quinones 2, 3, and 1 and the "half- clip" quinones 4, 5, and 6 with an increasing number of rings in the anellated aromatic unit (from benzene to anthracene) is the result of an increasing configuration interaction between a n → π* excitation of the quinoid component and a π → π* excitation with intramolecular charge transfer (CT) character. The initial π orbitals involved here and in higher lying transitions mainly stem from through-space interactions between π orbitals of the aromatic sidewalls and π orbitals of the quinone moiety with varying degree of mixing. The configuration interaction in the excited states can be considered to be a homoconjugation, that is, the relevant charge transfer states are formed across an allegedly insulating aliphatic bridge. The UV/vis spectra of the molecular clips 1-3, the "half-clips" 4-6, and the quinones 32 and 33 simulated by means of quantum chemical ab initio calculations agree well with the experimental spectra. © 2010 American Chemical Society.
    view abstractdoi: 10.1021/ja910362j
  • 2010 • 46 The effect of radiation processing and filler morphology on the biomechanical stability of a thermoset polyester composite
    Jayabalan, M. and Shalumon, K.T. and Mitha, M.K. and Ganesan, K. and Epple, M.
    Biomedical Materials 5 (2010)
    The effect of radiation processing and filler morphology on the biodegradation and biomechanical stability of a poly(propylene fumarate)/hydroxyapatite composite was investigated. Radiation processing influenced both cross-linking and biodegradation of the composites. Irradiation with a dose of 3 Mrad resulted in enhanced cross-linking, mechanical properties and a higher storage modulus which are favourable for dimensional stability of the implant. The particle morphology of the added hydroxyapatite in the highly cross-linked state significantly influenced the biomechanical and interfacial stability of the composites. Reorganization of agglomerated hydroxyapatite occurred in the cross-linked polymeric matrix under dynamic mechanical loading under simulated physiological conditions. Such a reorganization may increase the damping characteristics of the composite. © 2010 IOP Publishing Ltd.
    view abstractdoi: 10.1088/1748-6041/5/2/025009
  • 2010 • 45 Towards a high potential biocathode based on direct bioelectrochemistry between horseradish peroxidase and hierarchically structured carbon nanotubes
    Jia, W. and Schwamborn, S. and Jin, C. and Xia, W. and Muhler, M. and Schuhmann, W. and Stoica, L.
    Physical Chemistry Chemical Physics 12 10088-10092 (2010)
    Adsorption of horseradish peroxidase (HRP) on graphite rod electrodes sequentially modified with carbon microfibers (CMF) carrying carbon nanotubes in a hierarchically structured arrangement and finally pyrene hexanoic acid (PHA) for improving hydrophilicity of the electrode surface is the basis for the direct bioelectrocatalytic reduction of H 2O 2 at potentials as high as about +600 mV. The high-potential direct bioelectrocatalytic reduction of H 2O 2 is implying a direct bioelectrochemical communication between the Fe IVO,P + redox state known as compound I. The HRP loading was optimized leading to a current of 800 μA at a potential of 300 mV. © 2010 the Owner Societies.
    view abstractdoi: 10.1039/c0cp00349b
  • 2010 • 44 Probing the reactivity of ZnO and Au/ZnO nanoparticles by methanol adsorption: A TPD and DRIFTS study
    Kähler, K. and Holz, M.C. and Rohe, M. and Strunk, J. and Muhler, M.
    ChemPhysChem 11 2521-2529 (2010)
    The adsorption of methanol on pure ZnO and A--u-decorated ZnO nanoparticles and its thermal decomposition monitored by temperature-programmed desorption (TPD) experiments and by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), both applied under continuous flow conditions in fixed bed reactors, is reported. Two distinguishable methoxy species are formed during methanol adsorption on ZnO differing in the C-O stretching bands. During the subsequent TPD experiments two different H2peaks are observed, indicating the conversion of methoxy into formate species. By applying different heating rates, activation energies of 109 kJmol-1 and 127 kJmol-1 for the selective oxidation of the two methoxy species are derived. Correspondingly, the methoxy decomposition results in two distinguishable formate species, which are identified by the asymmetric and symmetric OCO stretching bands on pure ZnO and Au/ZnO. Based on the decreased intensities of the OH bands during methanol adsorption, which are specific for the various ZnO single crystal surfaces, on the different reactivities of these surfaces, and on the formate FTIR bands observed on ZnO single crystal surfaces, the two methoxy and the corresponding formate species are identified to be adsorbed on the exposed less reactive non-polar ZnO(101̄0) surface and on the highly reactive polar ZnO(0001̄) surface. The simultaneous formation of H2, CO, and CO2 at about 550-600 K during the TPD experiments indicate the decomposition of adsorbed formate species. The CO/CO2 ratio decreases with increasing Au loading, and a broad band due to electronic transitions from donor sites to the conduction band is observed in the DRIFT spectra for the Au-decorated ZnO nanoparticles. Thus, the presence of the Au nanoparticles results in an enhanced reducibility of ZnO facilitating the generation of oxygen vacancies. © 2010 Wiley-VCH Verlag GmbH& Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cphc.201000282
  • 2010 • 43 A Physicist's Perspective on "Views on Macroscopic Kinetics of Plasma Polymerisation"
    von Keudell, A. and Benedikt, J.
    Plasma Processes and Polymers 7 376--379 (2010)
    doi: 10.1002/ppap.201000011
  • 2010 • 42 Single shot damage mechanism of Mo/Si multilayer optics under intense pulsed XUV-exposure
    Khorsand, A.R. and Sobierajski, R. and Louis, E. and Bruijn, S. and Van Hattum, E.D. and Vande Kruijs, R.W.E. and Jurek, M. and Klinger, D. and Pelka, J.B. and Juha, L. and Burian, T. and Chalupsky, J. and Cihelka, J. and Hajkova,...
    Optics Express 18 700-712 (2010)
    We investigated single shot damage of Mo/Si multilayer coatings exposed to the intense fs XUV radiation at the Free-electron LASer facility in Hamburg - FLASH. The interaction process was studied in situ by XUV reflectometry, time resolved optical microscopy, and "post-mortem" by interference- polarizing optical microscopy (with Nomarski contrast), atomic force microscopy, and scanning transmission electron microcopy. An ultrafast molybdenum silicide formation due to enhanced atomic diffusion in melted silicon has been determined to be the key process in the damage mechanism. The influence of the energy diffusion on the damage process was estimated. The results are of significance for the design of multilayer optics for a new generation of pulsed (from atto- to nanosecond) XUV sources. © 2010 Optical Society of America.
    view abstractdoi: 10.1364/OE.18.000700
  • 2010 • 41 Quantitative visualization of colloidal and intracellular gold nanoparticles by confocal microscopy
    Klein, S. and Petersen, S. and Taylor, U. and Rath, D. and Barcikowski, S.
    Journal of Biomedical Optics 15 (2010)
    Gold nanoparticles (AuNPs) have the potential to become a versatile biomarker. For further use of AuNPs labeled with functionalized molecules, their visualization in biological systems by routine laboratory tools such as light microscopy is crucial. However, the size far below the diffraction limit affords specialized parameters for microscopical detection, which stimulated the current study, aimed to determine from which size onward AuNPs, either in dispersion or cell-associated, can be reliably detected by standard confocal microscopy. First, gold colloids of size-restricted fractions are examined in dispersion. At a minimum particle size of 60 nm, detection appears to be reliable. Particle counts in dilution series confirm these results by revealing single particle detection of 60-nm colloids. Second, AuNPs are visualized and quantified in cells, which interestingly cause a phase shift in the reflection of AuNPs. Gold mass spectroscopy confirms the number of AuNPs counted microscopically inside cells. Furthermore, it demonstrates for the first time a very high diffusion rate of 15-nm particles into the cells. In conclusion, the results back the suitability of confocal microscopy for the quantitative tracking of colloidal and intracellular gold nanoparticles sized 60 nm. © 2010 Society of Photo-Optical Instrumentation Engineers.
    view abstractdoi: 10.1117/1.3461170
  • 2010 • 40 Positively charged calcium phosphate/polymer nanoparticles for photodynamic therapy
    Klesing, J. and Wiehe, A. and Gitter, B. and Gräfe, S. and Epple, M.
    Journal of Materials Science: Materials in Medicine 21 887-892 (2010)
    The charge of nanoparticles influences their ability to pass through the cellular membrane, and a positive charge should be beneficial. The negative charge of calcium phosphate nanoparticles with an inner shell of carboxymethyl cellulose (CMC) was reversed by adding an outer shell of poly(ethyleneimine) (PEI) into which the photoactive dye 5,10,15,20-tetrakis(3-hydroxyphenyl)- porphyrin (mTHPP) was loaded. The aqueous dispersion of the nanoparticles was used for photodynamic therapy with HT29 cells (human colon adenocarcinoma cells), HIG-82 cells (rabbit synoviocytes), and J774A.1 cells (murine macrophages). A high photodynamic activity (killing) together with a very low dark toxicity was observed for HIG-82 and for J774.1 cells at 2 μM dye concentration. The killing efficiency was equivalent to the pure photoactive dye that, however, needs to be administered in alcoholic solution. © 2009 Springer Science+Business Media, LLC.
    view abstractdoi: 10.1007/s10856-009-3934-7
  • 2010 • 39 Biofuel combustion chemistry: From ethanol to biodiesel
    Kohse-Höinghaus, K. and Oßwald, P. and Cool, T.A. and Kasper, T. and Hansen, N. and Qi, F. and Westbrook, C.K. and Westmoreland, P.R.
    Angewandte Chemie - International Edition 49 3572-3597 (2010)
    Biofuels, such as bio-ethanol, bio-butanol, and biodiesel, are of increasing interest as alternatives to petroleum-based transportation fuels because they offer the long-term promise of fuel-source regenerability and reduced climatic impact. Current discussions emphasize the processes to make such alternative fuels and fuel additives, the compatibility of these substances with current fuel-delivery infrastructure and engine performance, and the competition between biofuel and food production. However, the combustion chemistry of the compounds that constitute typical biofuels, including alcohols, ethers, and esters, has not received similar public attention. Herein we highlight some characteristic aspects of the chemical pathways in the combustion of prototypical representatives of potential biofuels. The discussion focuses on the decomposition and oxidation mechanisms and the formation of undesired, harmful, or toxic emissions, with an emphasis on transportation fuels. New insights into the vastly diverse and complex chemical reaction networks of biofuel combustion are enabled by recent experimental investigations and complementary combustion modeling. Understanding key elements of this chemistry is an important step towards the intelligent selection of next-generation alternative fuels. © 2010 Wiley-VCH Verlag GmbH & Co. KCaA.
    view abstractdoi: 10.1002/anie.200905335
  • 2010 • 38 Electrochemical synthesis of core-shell catalysts for electrocatalytic applications
    Kulp, C. and Chen, X. and Puschhof, A. and Schwamborn, S. and Somsen, C. and Schuhmann, W. and Bron, M.
    ChemPhysChem 11 2854-2861 (2010)
    A novel electrochemical method to prepare platinum shells around carbon-supported metal nanoparticles (Ru and Au) by pulsed electrodeposition from solutions containing Pt ions is presented. Shell formation is confirmed by characteristic changes in the cyclic voltammograms, and is further evidenced by monitoring particle growth by transmission electron microscopy as well as by energy-dispersive analysis of X rays (EDX). Scanning electrochemical microscopy and EDX measurements indicate a selective Pt deposition on the metal/carbon catalyst, but not on the glassy carbon substrate. The thus prepared carbon-supported core-shell nanoparticles are investigated with regard to their activity in electrocatalytic oxygen reduction, which demonstrates the applicability of these materials in electrocatalysis or sensors. © 2010 Wiley-VCH Verlag GmbH& Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cphc.200900881
  • 2010 • 37 Nonlinear reaction coordinate analysis in the reweighted path ensemble
    Lechner, W. and Rogal, J. and Juraszek, J. and Ensing, B. and Bolhuis, P.G.
    Journal of Chemical Physics 133 (2010)
    We present a flexible nonlinear reaction coordinate analysis method for the transition path ensemble based on the likelihood maximization approach developed by Peters and Trout [J. Chem. Phys. 125, 054108 (2006)]. By parametrizing the reaction coordinate by a string of images in a collective variable space, we can optimize the likelihood that the string correctly models the committor data obtained from a path sampling simulation. The collective variable space with the maximum likelihood is considered to contain the best description of the reaction. The use of the reweighted path ensemble [J. Rogal, J. Chem. Phys. 133, 174109 (2010)] allows a complete reaction coordinate description from the initial to the final state. We illustrate the method on a z-shaped two-dimensional potential. While developed for use with path sampling, this analysis method can also be applied to regular molecular dynamics trajectories. © 2010 American Institute of Physics.
    view abstractdoi: 10.1063/1.3491818
  • 2010 • 36 Deformation of liquid-filled calcium alginate capsules in a spinning drop apparatus
    Leick, S. and Henning, S. and Degen, P. and Suter, D. and Rehage, H.
    Physical Chemistry Chemical Physics 12 2950-2958 (2010)
    This paper describes the mechanical properties of thin-walled, liquid-filled calcium alginate capsules by measuring the deformation of these particles in a spinning drop apparatus. By variation of the guluronic acid content of the alginate, the polymerization time and the calcium and alginate concentration we systematically studied the elastic properties of these capsules. In a series of experiments we observed for the first time new types of irreversibly deformed capsules, which can be described by plastic deformation. For comparison purposes, we also investigated liquid-filled calcium alginate particles in squeezing capsule experiments. The qualitative and quantitative results of both experiments in terms of the deformation properties and the surface Young moduli were in good agreement. Furthermore we also investigated liquid-filled calcium alginate particles by NMR microscopy to characterize the capsules in view of their membrane thickness. These results, in combination with the spinning capsule experiments allowed us to measure the kinetics of surface gelation and the mechanism of membrane growing. © 2010 the Owner Societies.
    view abstractdoi: 10.1039/b921116k
  • 2010 • 35 Online dual gradient reversed-phase/porous graphitized carbon nanoHPLC for proteomic applications
    Lewandrowski, U. and Sickmann, A.
    Analytical Chemistry 82 5391-5396 (2010)
    The analysis of proteolytic peptide mixtures is among the dominant tasks within proteomic workflows. In order to limit undersampling effects during mass spectrometric detection, online-coupled liquid chromatography is the method of choice, with reversed-phase chromatography being the most important separation mode. Since hydrophilic compounds such as short peptides and some glycosylated species as well as oligosaccharides from glycoproteomic workflows are commonly not accessible by this analytical setup, we hereby present a dual gradient system combining reversed-phase and porous graphitic carbon retention modes within a single nanoHPLC setup. Samples in the low femtomole range are analyzed consecutively first by reversed phase, and nonretained molecules are directly separated by porous graphitic carbon. Both gradient elution systems allow for online coupled mass spectrometric detection and are demonstrated to enable analysis of protein, peptide, and oligosaccharide mixtures within the same setup. Thereby, the accessible range for proteomic and glycoproteomic applications may be extended far beyond the limits of conventional reversed-phase nanoHPLC setups. © 2010 American Chemical Society.
    view abstractdoi: 10.1021/ac100853w
  • 2010 • 34 Kynurenine inhibits chondrocyte proliferation and is increased in synovial fluid of patients with septic arthritis
    Lögters, T.T. and Laryea, M.D. and Jäger, M. and Schädel-Höpfner, M. and Windolf, J. and Flohé, S. and Altrichter, J. and Scholz, M. and Paunel-Görgülü, A.N.
    Journal of Orthopaedic Research 28 1490-1496 (2010)
    Kynurenine, the major degradation product of tryptophan has been shown to directly damage various tissues. Its potential contribution to septic arthritis is unknown. In this study, we analyzed the putative diagnostic value of kynurenine for bacterial joint infection and its potential harmful effects on cartilage. In a prospective study 41 patients with a joint effusion who had undergone arthrocentesis were included. Tryptophan and kynurenine levels from synovial fluid were quantified by HPLC. Diagnostic value of kynurenine was evaluated and its effects on the proliferation of the chondrocyte cell line ATDC5 were determined. Synovial fluid kynurenine values from patients with septic arthritis (4.1 ± 0.8 μmol/L, n = 9) were significantly increased compared to patients with non-infectious inflammatory arthropathy (1.8 ± 0.2 μmol/L, n = 17) or osteoarthritis (1.2 ± 0.1 μmol/L, n = 15, p < 0.01). At a cut-off value of 2.28 μmol/L kynurenine had a sensitivity of 0.89 and a specificity of 0.87. Further, kynurenine inhibited chondrocyte (ATDC5) cell proliferation in a dose-dependent manner. Septic arthritis is associated with significantly increased values of synovial kynurenine. Furthermore kynurenine inhibits proliferation of chondrocytes, which strongly suggests a pathophysiological effect of kynurenine on cartilage in inflammatory arthropathies. © 2010 Orthopaedic Research Society.
    view abstractdoi: 10.1002/jor.21158
  • 2010 • 33 Easy synthesis of hollow polymer, carbon, and graphitized microspheres
    Lu, A.-H. and Li, W.-C. and Hao, G.-P. and Spliethoff, B. and Bongard, H.-J. and Schaack, B.B. and Schüth, F.
    Angewandte Chemie - International Edition 49 1615-1618 (2010)
    "Chemical Equation Presented" Balls galorel A new approach was developed for the easy synthesis of hollow microspheres with amorphous or graphitized microstructure. Starting from one type of solid polymer sphere, a simple water washing treatment led to the formation of hollow structures. Diverse products such as hollow carbon or graphitized spheres can be obtained, depending on subsequent treatment methods (see picture). © 2010 Wlley-VCH Verlag GmbH & Co. KGaA.
    view abstractdoi: 10.1002/anie.200906445
  • 2010 • 32 Combining independent drug classes into superior, synergistically acting hybrid molecules
    Müller-Schiffmann, A. and Andreyeva, A. and Rönicke, R. and Bartnik, D. and Brener, O. and Kutzsche, J. and Horn, A.H.C. and Hellmert, M. and Polkowska, J. and Gottmann, K. and Reymann, K.G. and Funke, S.A. and Nagel-Steger, L. ...
    Angewandte Chemie - International Edition 49 8743-8746 (2010)
    More than the sum of its parts: Novel hybrid compounds consisting of an organic β-sheet-breaking moiety and a signaling, D-enantiomeric Aβ-recognizing peptide moiety have been designed (see picture). The compounds, which were chemically synthesized and characterized by several techniques, combine rational design and drug selection from libraries and inhibit Aβ oligomerization and Aβ-induced synaptic pathology. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201004437
  • 2010 • 31 Modulation of aggregate size- and shape-distributions of the amyloid-β peptide by a designed β-sheet breaker
    Nagel-Steger, L. and Demeler, B. and Meyer-Zaika, W. and Hochdörffer, K. and Schrader, T. and Willbold, D.
    European Biophysics Journal 39 415-422 (2010)
    A peptide with 42 amino acid residues (Aβ42) plays a key role in the pathogenesis of the Alzheimer's disease. It is highly prone to self aggregation leading to the formation of fibrils which are deposited in amyloid plaques in the brain of diseased individuals. In our study we established a method to analyze the aggregation behavior of the Aβ peptide with a combination of sedimentation velocity centrifugation and enhanced data evaluation software as implemented in the software package UltraScan. Important information which becomes accessible by this methodology is the s-value distribution and concomitantly also the shape-distribution of the Aβ peptide aggregates generated by self-association. With this method we characterized the aggregation modifying effect of a designed bsheet breaker molecule. This compound is built from three head-to-tail connected aminopyrazole moieties and represents a derivative of the already described Tripyrazole. By addition of this compound to a solution of the Aβ42 peptide the maximum of the s-value distribution was clearly shifted to smaller s-values as compared to solutions where only the vehicle DMSO was added. This shift to smaller s-values was stable for at least 7 days. The information about size- and shape-distributions present in aggregated Aβ42 solutions was confirmed by transmission electron microscopy and by measurement of amyloid formation by thioflavin T fluorescence. © European Biophysical Societies' Association 2009.
    view abstractdoi: 10.1007/s00249-009-0416-2
  • 2010 • 30 4D shearforce-based constant-distance mode scanning electrochemical microscopy
    Nebel, M. and Eckhard, K. and Erichsen, T. and Schulte, A. and Schuhmann, W.
    Analytical Chemistry 82 7842-7848 (2010)
    4D shearforce-based constant-distance mode scanning electrochemical microscopy (4D SF/CD-SECM) is designed to assess SECM tip currents at several but constant distances to the sample topography at each point of the x,y-scanning grid. The distance dependent signal is achieved by a shearforce interaction between the in-resonance vibrating SECM tip and the sample surface. A 4D SF/CD-SECM measuring cycle at each grid point involves a shearforce controlled SECM tip z-approach to a point of closest distance and subsequent stepwise tip retractions. At the point of closest approach and during the retraction steps, pairs of tip current (I) and position are acquired for various distances above the sample surface. Such a sequence provides x,y,I maps, that can be compiled and displayed for each selected data acquisition distance. Thus, multiple SECM images are obtained at known and constant distances above the sample topography. 4D SF/CD-SECM supports distance-controlled tip operation while continuous scanning of the SECM tip in the shear-force distance is avoided. In this way, constant-distance mode SECM imaging can be performed at user-defined, large tip-to-sample distances. The feasibility and the potential of the proposed 4D SF/CD-SECM imaging is demonstrated using on the one hand amperometric feedback mode imaging of a Pt band electrode array and on the other hand the visualization of the diffusion zone of a redox active species above a microelectrode in a generator/collector arrangement. © 2010 American Chemical Society.
    view abstractdoi: 10.1021/ac1008805
  • 2010 • 29 Revealing the design principles of high-performance biological composites using Ab initio and multiscale simulations: The example of lobster cuticle
    Nikolov, S. and Petrov, M. and Lymperakis, L. and Friák, M. and Sachs, C. and Fabritius, H.-O. and Raabe, D. and Neugebauer, J.
    Advanced Materials 22 519-526 (2010)
    Natural materials are hierarchically structured nanocomposites. A bottom-up multiscale approach to model the mechanical response of the chitin-based mineralized cuticle material of Homarus americanus is presented, by combining quantummechanical ab initio calculations with hierarchical homogenization. The simulations show how the mechanical properties are transferred from the atomic scale through a sequence of specifically designed microstructures to realize optimal stiffness. (Figure Presented) © 2010 WILEY-VCH Verlag GmbH & Co. KGaA,.
    view abstractdoi: 10.1002/adma.200902019
  • 2010 • 28 Development of molecular and solid catalysts for the direct low-temperature oxidation of methane to methanol
    Palkovits, R. and von Malotki, C. and Baumgarten, M. and Müllen, K. and Baltes, C. and Antonietti, M. and Kuhn, P. and Weber, J. and Thomas, A. and Schüth, F.
    ChemSusChem 3 277-282 (2010)
    The direct low-temperature oxidation of methane to methanol is demonstrated on a highly active homogeneous molecular catalyst system and on heterogeneous molecular catalysts based on polymeric materials possessing ligand motifs within the material structure. The N-(2-methylpropyl)-4,5-diazacarbazolyl-dichloro-platinum(II) complex reaches significantly higher activity compared to the well-known Periana system and allows first conclusions on electronic and structural requirements for high catalytic activity in this reaction. Interestingly, comparable activities could be achieved utilizing a platinum modified poly(benzimidazole) material, which demonstrates for the first time a solid catalyst with superior activity compared to the Periana system. Although the material shows platinum leaching, improved activity and altered electronic properties, compared to the conventional Periana system, support the proposed conclusions on structure-activity relationships. In comparison, platinum modified triazine-based catalysts show lower catalytic activity, but rather stable platinum coordination even after several catalytic cycles. Based on these systems, further development of improved solid catalysts for the direct low-temperature oxidation of methane to methanol is feasible. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.200900123
  • 2010 • 27 Sticking polydisperse hydrophobic magnetite nanoparticles to lipid membranes
    Paulus, M. and Degen, P. and Brenner, T. and Tiemeyer, S. and Struth, B. and Tolan, M. and Rehage, H.
    Langmuir 26 15945-15947 (2010)
    The formation of a layer of hydrophobic magnetite (Fe3O 4) nanoparticles stabilized by lauric acid is analyzed by in situ X-ray reflectivity measurements. The data analysis shows that the nanoparticles partially disperse their hydrophobic coating. Consequently, a Langmuir layer was formed by lauric acid molecules that can be compressed into an untilted condensed phase. A majority of the nanoparticles are attached to the Langmuir film integrating lauric acid residue on their surface into the Langmuir film. Hence, the particles at the liquid-gas interface can be identified as so-called Janus beads, which are amphiphilic solids having two sides with different functionality. © 2010 American Chemical Society.
    view abstractdoi: 10.1021/la102882j
  • 2010 • 26 Nanoscale engineering and optical addressing of single spins in diamond
    Pezzagna, S. and Wildanger, D. and Mazarov, P. and Wieck, A.D. and Sarov, Y. and Rangelow, I. and Naydenov, B. and Jelezko, F. and Hell, S.W. and Meijer, J.
    Small 6 2117-2121 (2010)
    The artificial creation of shallow nitrogen-vacancy (NV) centres in diamond with 25 nm lateral resolution is performed by collimated implantation of low-energy nitrogen ions. The electron spin associated to this defect is the most promising qubit for a scalable quantum computer working at room temperature. Individual optical addressing of two single centres separated by only 16 nm is demonstrated with stimulated emission depletion (STED) microscopy.
    view abstractdoi: 10.1002/smll.201000902
  • 2010 • 25 An integrated catalytic approach to fermentable sugars from cellulose
    Rinaldi, R. and Engel, P. and Büchs, J. and Spiess, A.C. and Schüth, F.
    ChemSusChem 3 1151-1153 (2010)
    The production of fermentable sugars from cellulose in almost quantitative yield is accelerated. Starting from cello-oligomers obtained by acid hydrolysis of cellulose in an ionic liquid, the catalytic approach described herein, integrating acid and enzymatic catalysis, quantitatively converts cellulose to fermentable sugars (glucose and cellobiose) within only a few hours. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.201000153
  • 2010 • 24 Which controls the depolymerization of cellulose in ionic liquids: The solid acid catalyst or cellulose?
    Rinaldi, R. and Meine, N. and vom Stein, J. and Palkovits, R. and Schüth, F.
    ChemSusChem 3 266-276 (2010)
    Cellulose is a renewable and widely available feedstock. It is a biopolymer that is typically found in wood, straw, grass, municipal solid waste, and crop residues. Its use as raw material for biofuel production opens up the possibility of sustainable biorefinery schemes that do not compete with food supply. Tapping into this feedstock for the production of biofuels and chemicals requires-as the first-step-its depolymerization or its hydrolysis into intermediates that are more susceptible to chemical and/or biological transformations. We have shown earlier that solid acids selectively catalyze the depolymerization of cellulose solubilized in 1-butyl-3-methylimidazolium chloride (BMIMCl) at 100°C. Here, we address the factors responsible for the control of this reaction. Both cellulose and solid acid catalysts have distinct and important roles in the process. Describing the depolymerization of cellulose by the equivalent number of scissions occurring in the cellulosic chains allows a direct correlation between the product yields and the extent of the polymer breakdown. The effect of the acid strength on the depolymerization of cellulose is discussed in detail. Practical aspects of the reaction, concerning the homogeneous nature of the catalysis in spite of the use of a solid acid catalyst, are thoroughly addressed. The effect of impurities present in the imidazolium-based ionic liquids on the reaction performance, the suitability of different ionic liquids as solvents, and the recyclability of Amberlyst 15DRY and BMIMCl are also presented. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cssc.200900281
  • 2010 • 23 PH-Switchable vesicles from a serine-derived guanidiniocarbonyl pyrrole carboxylate zwitterion in DMSO
    Rodler, F. and Linders, J. and Fenske, T. and Rehm, T. and Mayer, C. and Schmuck, C.
    Angewandte Chemie - International Edition 49 8747-8750 (2010)
    Tightly closed: Zwitterion 1 forms vesicles that have an approximate size of 50nm in DMSO solution. The vesicles can be opened and closed by the addition of either acid or base, as vesicle formation depends on the protonation state of zwitterion 1 (see picture). The membrane permeability of the vesicles is surprisingly low: the encapsulated solvent does not exchange with the surrounding solution, even on a time scale of a few hundred milliseconds. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201003405
  • 2010 • 22 The reweighted path ensemble
    Rogal, J. and Lechner, W. and Juraszek, J. and Ensing, B. and Bolhuis, P.G.
    Journal of Chemical Physics 133 (2010)
    We introduce a reweighting scheme for the path ensembles in the transition interface sampling framework. The reweighting allows for the analysis of free energy landscapes and committor projections in any collective variable space. We illustrate the reweighting scheme on a two dimensional potential with a nonlinear reaction coordinate and on a more realistic simulation of the Trp-cage folding process. We suggest that the reweighted path ensemble can be used to optimize possible nonlinear reaction coordinates. © 2010 American Institute of Physics.
    view abstractdoi: 10.1063/1.3491817
  • 2010 • 21 Unique features of the folding landscape of a repeat protein revealed by pressure perturbation
    Rouget, J.-B. and Schroer, M.A. and Jeworrek, C. and Pühse, M. and Saldana, J.-L. and Bessin, Y. and Tolan, M. and Barrick, D. and Winter, R. and Royer, C.A.
    Biophysical Journal 98 2712-2721 (2010)
    The volumetric properties of proteins yield information about the changes in packing and hydration between various states along the folding reaction coordinate and are also intimately linked to the energetics and dynamics of these conformations. These volumetric characteristics can be accessed via pressure perturbation methods. In this work, we report high-pressure unfolding studies of the ankyrin domain of the Notch receptor (Nank1-7) using fluorescence, small-angle x-ray scattering, and Fourier transform infrared spectroscopy. Both equilibrium and pressure-jump kinetic fluorescence experiments were consistent with a simple two-state folding/unfolding transition under pressure, with a rather small volume change for unfolding compared to proteins of similar molecular weight. High-pressure fluorescence, Fourier transform infrared spectroscopy, and small-angle x-ray scattering measurements revealed that increasing urea over a very small range leads to a more expanded pressure unfolded state with a significant decrease in helical content. These observations underscore the conformational diversity of the unfolded-state basin. The temperature dependence of pressure-jump fluorescence relaxation measurements demonstrated that at low temperatures, the folding transition state ensemble (TSE) lies close in volume to the folded state, consistent with significant dehydration at the barrier. In contrast, the thermal expansivity of the TSE was found to be equivalent to that of the unfolded state, indicating that the interactions that constrain the folded-state thermal expansivity have not been established at the folding barrier. This behavior reveals a high degree of plasticity of the TSE of Nank1-7. © 2010 by the Biophysical Society.
    view abstractdoi: 10.1016/j.bpj.2010.02.044
  • 2010 • 20 Orthogonal protein decoration of DNA origami
    Saccà, B. and Meyer, R. and Erkelenz, M. and Kiko, K. and Arndt, A. and Schroeder, H. and Rabe, K.S. and Niemeyer, C.M.
    Angewandte Chemie - International Edition 49 9378-9383 (2010)
    If the face fits: Self-labeling fusion proteins have been used for the site-specific decoration of DNA origami. This method even allows individual faces of the quasi-two-dimensional plane of the nanostructure to be specifically decorated (see picture), thereby enabling directional immobilization and thus control over the accessibility of distinct proteins presented on the structure. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201005931
  • 2010 • 19 Hydrogen vibrational modes on graphene and relaxation of the C-H stretch excitation from first-principles calculations
    Sakong, S. and Kratzer, P.
    Journal of Chemical Physics 133 (2010)
    Density functional theory (DFT) calculations are used to determine the vibrational modes of hydrogen adsorbed on graphene in the low-coverage limit. Both the calculated adsorption energy of a H atom of 0.8 eV and calculated C-H stretch vibrational frequency of 2552 cm-1 are unusually low for hydrocarbons, but in agreement with data from electron energy loss spectroscopy on hydrogenated graphite. The clustering of two adsorbed H atoms observed in scanning tunneling microscopy images shows its fingerprint also in our calculated spectra. The energetically preferred adsorption on different sublattices correlates with a blueshift of the C-H stretch vibrational modes in H adatom clusters. The C-H bending modes are calculated to be in the 1100 cm-1 range, resonant with the graphene phonons. Moreover, we use our previously developed methods to calculate the relaxation of the C-H stretch mode via vibration-phonon interaction, using the Born-Oppenheimer surface for all local modes as obtained from the DFT calculations. The total decay rate of the H stretch into other H vibrations, thereby creating or annihilating one graphene phonon, is determined from Fermi's golden rule. Our calculations using the matrix elements derived from DFT calculations show that the lifetime of the H stretch mode on graphene is only several picoseconds, much shorter than on other semiconductor surfaces such as Ge(001) and Si(001). © 2010 American Institute of Physics.
    view abstractdoi: 10.1063/1.3474806
  • 2010 • 18 Micro- and nanopatterning of functional organic monolayers on oxide-free silicon by laser-induced photothermal desorption
    Scheres, L. and Klingebiel, B. and Ter Maat, J. and Giesbers, M. and De Jong, H. and Hartmann, N. and Zuilhof, H.
    Small 6 1918-1926 (2010)
    The photothermal laser patterning of functional organic monolayers, prepared on oxide-free hydrogen-terminated silicon, and subsequent backfi lling of the laser-written lines with a second organic monolayer that differs in its terminal functionality, is described. Since the thermal monolayer decomposition process is highly nonlinear in the applied laser power density, subwavelength patterning of the organic monolayers is feasible. After photothermal laser patterning of hexadecenyl monolayers, the lines freed up by the laser are backfi lled with functional acid fl uoride monolayers. Coupling of cysteamine to the acid fl uoride groups and subsequent attachment of Au nanoparticles allows easy characterization of the functional lines by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Depending on the laser power and writing speed, functional lines with widths between 1.1 μm and 250 nm can be created. In addition, trifl uoroethyl-terminated (TFE) monolayers are also patterned. Subsequently, the decomposed lines are backfi lled with a nonfunctional hexadecenyl monolayer, the TFE stripes are converted into thiol stripes, and then finally covered with Au nanoparticles. By reducing the lateral distance between the laser lines, Au-nanoparticle stripes with widths close to 100 nm are obtained. Finally, in view of the great potential of this type of monolayer in the fi eld of biosensing, the ease of fabricating biofunctional patterns is demonstrated by covalent binding of fl uorescently labeled oligo-DNA to acidfl uoride-backfi lled laser lines, which-as shown by fl uorescence microscopy-is accessible for hybridization.Copyright © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/smll.201000189
  • 2010 • 17 Platinum nanoparticles: The crucial role of crystal face and colloid stabilizer in the diastereoselective hydrogenation of cinchonidine
    Schmidt, E. and Kleist, W. and Krumeich, F. and Mallat, T. and Baiker, A.
    Chemistry - A European Journal 16 2181-2192 (2010)
    The preparation of stable metal nanoparticles requires a strong interaction between the (organic) stabilizer and the metal surface that might alter the catalytic properties. This behavior has been described as "poisoning" since the stabilizer normally decreases the catalytic activity due to site blocking. Here we show a striking influence of the stabilizer on the selectivity in the hydrogenation of cinchonidine (CD) over poly(acrylic acid) (PAA)-stabilized Pt nanoparticles with well-defined shape distributions. In the hydrogenation of the heteroaromatic ring of cinchonidine in toluene, the diastereomeric excess of the (S)-hexahydrocinchonidine increased upon increasing Pt{111}/Pt{100} ratio, but this distinct shape selectivity was observed only after the oxidative removal of PAA at 473 K. The use of the as-prepared nanoparticles inverted the major diastereomer to R, and this isomer was formed also in acetic acid. This striking change in the diastereoselectivity indicates that poly(acrylic acid), which remains on the Pt surface after preparation, interacts with CD during hydrogenation almost as strongly as the solvent acetic acid. The PAA stabilizer plays a dual role: it allows one to control the size and shape of the nanoparticles during their synthesis, and it affects the rate and diastereoselectivity of the hydrogenation of CD probably through a "surface-localized acidification". © 2010 Wiley-VCH Verlag GmbH & Co. KGaA,.
    view abstractdoi: 10.1002/chem.200902517
  • 2010 • 16 High-pressure SAXS study of folded and unfolded ensembles of proteins
    Schroer, M.A. and Paulus, M. and Jeworrek, C. and Krywka, C. and Schmacke, S. and Zhai, Y. and Wieland, D.C.F. and Sahle, C.J. and Chimenti, M. and Royer, C.A. and Garcia-Moreno, B. and Tolan, M. and Winter, R.
    Biophysical Journal 99 3430-3437 (2010)
    A structural interpretation of the thermodynamic stability of proteins requires an understanding of the structural properties of the unfolded state. High-pressure small-angle x-ray scattering was used to measure the effects of temperature, pressure, denaturants, and stabilizing osmolytes on the radii of gyration of folded and unfolded state ensembles of staphylococcal nuclease. A set of variants with the internal Val-66 replaced with Ala, Tyr, or Arg was used to examine how changes in the volume and polarity of an internal microcavity affect the dimensions of the native state and the pressure sensitivity of the ensemble. The unfolded state ensembles achieved for these proteins with high pressure were more compact than those achieved at high temperature, and were all very sensitive to the presence of urea and glycerol. Substitutions at the hydrophobic core detectably altered the conformation of the protein, even in the folded state. The introduction of a charged residue, such as Arg, inside the hydrophobic interior of a protein could dramatically alter the structural properties, even those of the unfolded state. The data suggest that a charge at an internal position can interfere with the formation of transient hydrophobic clusters in the unfolded state, and ensure that the pressure-unfolded form of a protein occupies the maximum volume possible. Only at high temperatures does the radius of gyration of the unfolded state ensemble approach the value for a statistical random coil. © 2010 by the Biophysical Society.
    view abstractdoi: 10.1016/j.bpj.2010.09.046
  • 2010 • 15 Paving the way to new energy systems: The key role of the chemical sciences
    Schüth, F.
    ChemSusChem 3 6-8 (2010)
    doi: 10.1002/cssc.200900272
  • 2010 • 14 Synthesis of glass-coated SERS nanoparticle probes via SAMs with terminal SiO2 precursors
    Schütz, M. and Küstner, B. and Bauer, M. and Schmuck, C. and Schlücker, S.
    Small 6 733-737 (2010)
    A short synthesis route to silica-encapsulated nanoparticles coated with a self-assembled monolayer (SAM) is presented. The organic molecules within the SAM contain a SiO2 precursor to render the surface vitreophilic. Due to the high mechanical and chemical stability of a glass shell, such particles can be used as probes in targeted research with surface-enhanced Raman scattering as the read-out method. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/smll.200902065
  • 2010 • 13 Patterned CNT arrays for the evaluation of oxygen reduction activity by SECM
    Schwamborn, S. and Stoica, L. and Chen, X. and Xia, W. and Kundu, S. and Muhler, M. and Schuhmann, W.
    ChemPhysChem 11 74-78 (2010)
    doi: 10.1002/cphc.200900744
  • 2010 • 12 Dissociation of oxygen on Ag(100) induced by inelastic electron tunneling
    Sprodowski, C. and Mehlhorn, M. and Morgenstern, K.
    Journal of Physics Condensed Matter 22 (2010)
    Scanning tunneling microscopy (STM) is used to study the dissociation of molecular oxygen on Ag(100) induced by inelastic electron tunneling (IET) at 5 K. This dissociation is possible above 3.3 V with a yield of (3.63 ± 0.47) × 10-9 per electron. Dissociation leads to three different types of hot atom motion: lateral motion, a cannon ball mechanism, and abstractive dissociation. Analysis of the I -t characteristics during dissociation suggests that the dissociation is proceeded by an adsorption site change. © 2010 IOP Publishing Ltd.
    view abstractdoi: 10.1088/0953-8984/22/26/264005
  • 2010 • 11 Observation of breathing-like modes in an individual multiwalled carbon nanotube
    Spudat, C. and Müller, M. and Houben, L. and Maultzsch, J. and Goss, K. and Thomsen, C. and Schneider, C.M. and Meyer, C.
    Nano Letters 10 4470-4474 (2010)
    We study collective vibrational breathing modes in the Raman spectrum of a multiwalled carbon nanotube. In correlation with high-resolution transmission electron microscopy, we find that these modes have energies differing by more than 23% from the radial breathing modes of the corresponding single-walled nanotubes. This shift in energy is explained with intershell interactions using a model of coupled harmonic oscillators. The strength of this interaction is related to the coupling strength expected for few-layer graphene. © 2010 American Chemical Society.
    view abstractdoi: 10.1021/nl102305a
  • 2010 • 10 Nonendosomal cellular uptake of ligand-free, positively charged gold nanoparticles
    Taylor, U. and Klein, S. and Petersen, S. and Kues, W. and Barcikowski, S. and Rath, D.
    Cytometry Part A 77 439-446 (2010)
    Gold nanoparticles (GNPs) have interesting optical properties, such as exceptionally high quantum yields and virtually limitless photostability. Therefore, they show the potential for applications as biomarkers especially suitable for in vivo and long-term studies. The generation of GNPs using pulsed laser light rather than chemical means provides nanoparticles, which are remarkably stable in a variety of media without the need of stabilizing agents or ligands. This stabilization is achieved by partial oxidation of the gold surface resulting in positively charged GNPs. However, little is known about cellular uptake of such ligand-free nanoparticles, their intracellular fate, or cell viability after nanoparticle contact. The current work is aimed to explore the response of a bovine cell line to GNP exposure mainly using laser scanning confocal microscopy (LSCM) supported by other techniques. Cultured bovine immortalized cells (GM7373) were coincubated with GNP (average diameter 15 nm, 50 μM Au) for 2, 24, and 48 h. The detection of GNP-associated light scattering by the LSCM facilitated a clear distinction between GNP-containing cells and the negative controls. After 48 h, 75% of cells had visibly incorporated nanoparticles. No colocalization was detected with either Rab5a or Lamp1-positive structures, i.e., endosomes or lysosomes, respectivley. However, transmission electron microscope analysis of GNP-coincubated cells indicated the nanoparticles to be positioned within electron-dense structures. Coincubation at 4°C did not inhibit nanoparticle uptake, suggesting diffusion as possible entrance mechanism. Although the assessment of cell morphology, membrane integrity, and apoptosis revealed no GNP-related loss of cell viability at a gold concentration of 25 μM or below, a cytotoxic effect was observed in a proliferation assay after exposing low cell numbers to 50 μM Au and above. In conclusion, this study confirmed the cellular uptake of ligand-free gold nanoparticles during coincubation apparently without using endocytic pathways. © 2010 International Society for Advancement of Cytometry.
    view abstractdoi: 10.1002/cyto.a.20846
  • 2010 • 9 Effect of surface charge distribution on the adsorption orientation of proteins to lipid monolayers
    Tiemeyer, S. and Paulus, M. and Tolan, M.
    Langmuir 26 14064-14067 (2010)
    The adsorption orientation of the proteins lysozyme and ribonuclease A (RNase A) to a neutral 1,2-dipalmitoyl-snglycero- 3-phosphocholine (DPPC) and a negatively charged stearic acid lipid film was investigated by means of X-ray reflectivity. Both proteins adsorbed to the negatively charged lipid monolayer, whereas at the neutral monolayer, no adsorption was observed. For acquiring comprehensive information on the proteins' adsorption, X-ray reflectivity data were combined with electron densities obtained from crystallographic data. With this method, it is possible to determine the orientation of adsorbed proteins in solution underneath lipid monolayers. While RNase A specifically coupled with its positively charged active site to the negatively charged lipid monolayer, lysozyme prefers an orientation with its long axis parallel to the Langmuir film. In comparison to the electrostatic maps of the proteins, our results can be explained by the discriminative surface charge distribution of lysozyme and RNase A. © 2010 American Chemical Society.
    view abstractdoi: 10.1021/la102616h
  • 2010 • 8 The influence of surface composition of nanoparticles on their interactions with serum albumin
    Treuel, L. and Malissek, M. and Gebauer, J.S. and Zellner, R.
    ChemPhysChem 11 3093-3099 (2010)
    Interactions between differently functionalised silver and gold nanoparticles (NPs) as well as polystyrene nanoparticles with bovine serum albumin (BSA) are studied using circular dichroism (CD) spectroscopy. It is found that the addition of NPs to the protein solution destroys part of the helical secondary structure of the protein as a result of surface adsorption. From the loss of free protein and hence the extent of their structural change adsorption equilibrium constants are derived. The results reveal that citrate-coated gold and silver NPs exhibit much stronger interactions with BSA than polymeric or polymer-coated metallic NPs. It is therefore concluded that for the particles considered, the influence of surface composition on the interaction behaviour dominates that of the core. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/cphc.201000174
  • 2010 • 7 Active transport of amino acids by a guanidiniocarbonyl-pyrrole receptor
    Urban, C. and Schmuck, C.
    Chemistry - A European Journal 16 9502-9510 (2010)
    Herein we report the synthesis and characterization of a transporter 9 for N-acetylated amino acids. Transporter 9 is a conjugate of a guanidiniocarbonyl pyrrole cation, one of the most efficient carboxylate binding motifs reported so far, and a hydrophobictris (dodecylbenzyl) group, which ensures solubility in organic solvents. In its protonated form, 9 binds N-acetylated amino acid carboxylates in wetorganic solvents with association constantsin the range of 104m-1 as estimated by extraction experiments. Aromatic amino acids are preferred due to additional cation-α-interactions of the amino acid side chain with the guanidiniocarbonyl pyrrole moiety. U-tube experiments established efficient transport across a bulk liquid chloroform phase with fluxes approaching 10-6 molm-2s-1. In experiments with single substrates, the release rate of the amino acid from the receptor-substrate complex at the interface with the receiving phase is rate determining. In contrast to this, in competition experiments with several substrates, the therm-odynamic affinity to 9 becomes decisive. As 9 can only transport anions in its protonated form and has a pKa value of approximately 7, pH-driven active transport of amino acids is also possible. Transport occurs as a symport of the amino acid carboxylate and a proton. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/chem.201000509
  • 2010 • 6 Identification of Thiazolidinones Spiro-Fused to IndoIin-2-ones as Potent and Selective Inhibitors of the Mycobacterium tuberculosis Protein Tyrosine Phosphatase B
    Vintonyak, V.V. and Warburg, K. and Kruse, H. and Grimme, S. and Hübet, K. and Rauh, D. and Waldmann, H.
    Angewandte Chemie - International Edition 49 5902-5905 (2010)
    (Figure Presented) The best of 40000: Detailed structureactivity- relationship studies revealed key structural elements of indolin-2-on-3- spirothiazolidinones (see example) and their appropriate configuration for strong inhibitory activity against the pathophysiologically relevant title protein. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/anie.201002138
  • 2010 • 5 Molecular recognition of vesicles: Host-guest interactions combined with specific dimerization of zwitterions
    Voskuhl, J. and Fenske, T. and Stuart, M.C.A. and Wibbeling, B. and Schmuck, C. and Ravoo, B.J.
    Chemistry - A European Journal 16 8300-8306 (2010)
    The aggregation of β-cyclodextrin vesicles can be induced by an adamantyl-substituted zwitterionic guanidiniocarbonylpyrrole carboxylate guest molecule (1). Upon addition of 1 to the cyclodextrin vesicles at neutral pH, the vesicles aggregate (but do not fuse), as shown by using UV/Vis and fluorescence spectroscopy, dynamic light scattering, ζ-potential measurements, cryogenic transmission electron microscopy, and atomic force microscopy. Aggregation of the vesicles is in-duced by a twofold supramolecular interaction. First, the adamantyl group of 1 forms an inclusion complex with ßcyclodextrin. Second, at neutral pH the guanidiniocarbonylpyrrole carboxylate zwitterion dimerizes through the formation of hydrogen-bonded ion pairs. Because the dimerization of 1 depends on the zwitterionic protonation state of 1, the aggregation of the cyclodextrin vesicles is also pH dependent; the cyclodextrin vesicles do not interact at pH 5 or 9, at which 1 is either cationic or anionic and, therefore, not self-complementary. These observations are consistent with molecular recognition of the vesicles through a combination of two different supramolecular interactions, that is, host-guest inclusion and dimerization of zwitterions, at the bilayer membrane surface. © 2010 Wiley-VCH Verlag GmbH& Co. KGaA, Weinheim.
    view abstractdoi: 10.1002/chem.201000623
  • 2010 • 4 A scaffold-tree-merging strategy for prospective bioactivity annotation of γ-pyrones
    Wetzel, S. and Wilk, W. and Chammaa, S. and Sperl, B. and Roth, A.G. and Yektaoglu, A. and Renner, S. and Berg, T. and Arenz, C. and Giannis, A. and Oprea, T.I. and Rauh, D. and Kaiser, M. and Waldmann, H.
    Angewandte Chemie - International Edition 49 3666-3670 (2010)
    Tactical target setting: The merging of natural product and non-natural product based hierarchical scaffold trees annotated with bioactivity (see schematic illustration) together with brachiation along structural lines of biological relevance provides a novel strategy for the prospective identification of protein targets for compound collections inspired by natural product structures. (Figure Presented) © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.
    view abstractdoi: 10.1002/anie.200906555
  • 2010 • 3 Reversible and noncompetitive inhibition of β-tryptase by protein surface binding of tetravalent peptide ligands identified from a combinatorial split-mix library
    Wich, P.R. and Schmuck, C.
    Angewandte Chemie - International Edition 49 4113-4116 (2010)
    (Figure Presented) Molecular plug: On-bead screening of a combinatorial library of 216 tetravalent oligopeptides reveals highly specific, noncompetitive inhibitors of the serine protease β-tryptase with nanomolar affinity. The ligands most likely bind to the protein surface and act as a molecular plug that blocks access to the active sites, which are buried inside a central cavity (see picture). © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.
    view abstractdoi: 10.1002/anie.200907221
  • 2010 • 2 Wear mechanisms in metal-on-metal bearings: The importance of tribochemical reaction layers
    Wimmer, M.A. and Fischer, A. and Büscher, R. and Pourzal, R. and Sprecher, C. and Hauert, R. and Jacobs, J.J.
    Journal of Orthopaedic Research 28 436-443 (2010)
    Metal-on-metal (MoM) bearings are at the forefront in hip resurfacing arthroplasty. Because of their good wear characteristics and design flexibility, MoM bearings are gaining wider acceptance with market share reaching nearly 10% worldwide. However, concerns remain regarding potential detrimental effects of metal particulates and ion release. Growing evidence is emerging that the local cell response is related to the amount of debris generated by these bearing couples. Thus, an urgent clinical need exists to delineate the mechanisms of debris generation to further reduce wear and its adverse effects. In this study, we investigated the microstructural and chemical composition of the tribochemical reaction layers forming at the contacting surfaces of metallic bearings during sliding motion. Using X-ray photoelectron spectroscopy and transmission electron microscopy with coupled energy dispersive X-ray and electron energy loss spectroscopy, we found that the tribolayers are nanocrystalline in structure, and that they incorporate organic material stemming from the synovial fluid. This process, which has been termed "mechanical mixing," changes the bearing surface of the uppermost 50 to 200 nm from pure metallic to an organic composite material. It hinders direct metal contact (thus preventing adhesion) and limits wear. This novel finding of a mechanically mixed zone of nanocrystalline metal and organic constituents provides the basis for understanding particle release and may help in identifying new strategies to reduce MoM wear. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
    view abstractdoi: 10.1002/jor.21020
  • 2010 • 1 Anti-nonspecific protein adsorption properties of biomimetic glycocalyx-like glycopolymer layers: Effects of glycopolymer chain density and protein size
    Yang, Q. and Kaul, C. and Ulbricht, M.
    Langmuir 26 5746-5752 (2010)
    In many cases, biomaterials surfaces are desired to be resistant to protein adsorption. A system fulfilling this task in nature is the so-called glycocalyx. The glycocalyx is an outer layer on the cell membrane with bound glycoproteins and glycolipids, exposing a pattern of carbohydrate groups. There is a growing interest to mimic this glycocalyx layer to have a tool to overcome the problems with uncontrolled protein adsorption on biomaterials. In this work a glycocalyx-like layer is artificially imitated by surface-initiated atom transfer radical polymerization (ATRP) of a glycomonomer, d-gluconamidoethyl methacrylate (GAMA), from a mixed self-assembled monolayer (SAM) of an ATRP initiator-immobilized hydroxyl-terminated thiol and a methyl-terminated thiol as diluent. Fourier transform infrared spectroscopy (FT/IR-ATR), contact angle, and ellipsometry measurements were employed to confirm the grafting of the glycopolymer. The anti-nonspecific protein binding pr