Karl Fischer

Johannes Gutenberg-Universität Mainz, Mayence, Rheinland-Pfalz, Germany

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Publications (74)394.41 Total impact

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    ABSTRACT: In this work, activated ester chemistry is employed to synthesize biocompatible and readily functionalizable polymersomes. Via aminolysis of pentafluorophenyl methacrylate-based precursor polymers, an N-(2-hydroxypropyl) methacrylamide (HPMA)-analog hydrophilic block is obtained. The precursor polymers can be versatile functionalized by simple addition of suitable primary amines during aminolysis as demonstrated using a fluorescent dye. Vesicle formation is proven by cryoTEM and light scattering. High encapsulation efficiencies for hydrophilic cargo like siRNA are achieved using dual centrifugation and safe encapsulation is demonstrated by gel electrophoresis. In vitro studies reveal low cytotoxicity and no protein adsorption-induced aggregation in human blood serum occurs, making the vesicles interesting candidates as nanosized drug carriers.
    Macromolecular Rapid Communications 10/2015; DOI:10.1002/marc.201500444 · 4.94 Impact Factor
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    ABSTRACT: Cylindrical brush polymers constitute promising polymeric drug delivery systems (nanoDDS). Because of the densely grafted side chains such structures may intrinsically exhibit little protein adsorption (“stealth” effect) while providing a large number of functional groups accessible for bioconjugation reactions. Polysarcosine (PSar) is a highly water-soluble, nonionic and nonimmunogenic polypeptoid based on the endogenous amino acid sarcosine (N-methyl glycine). Here we report on the synthesis, characterization and biocompatibility of cylindrical brush polymers with either polysarcosine side chains or poly-l-lysine-b-polysarcosine side chains. The latter leads to block copolypept(o)id based core-shell cylindrical brushes with a cationic poly-l-lysine (PLL) core and a neutral polysarcosine corona. The cylindrical brush polymers were prepared by ring-opening polymerization of the respective N-carboxyanhydrides (NCA) from a macroinitiator chain. Preliminary experiments on complex formation with siRNA demonstrate that a core-shell cylindrical brush polymer may complex on average up to 270 RNA molecules amounting to a high loading efficiency of N+/P- = 1.1. No bridging between cylindrical brushes leading to larger aggregates is observed. In vitro studies on the silencing of the expression of ApoB100, which is abundantly expressed in AML-12 hepatocytes, induced by siRNA-cylindrical core-shell brush complexes showed high efficiency, leading to a knock-down efficiency of ApoB100 mRNA of 70%.
    Macromolecules 04/2015; 48(7):2074-2086. DOI:10.1021/ma502497x · 5.80 Impact Factor
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    ABSTRACT: Multicomponent particles have emerged in recent years as new compartmentalized colloids with two sides of different chemistry or polarity that have opened up a wide field of unique applications in medicine, biochemistry, optics, physics and chemistry. A drawback of particles containing a ZnO hemisphere is their low stability in biological environment due to the amphoteric proper-ties of Zn2+. Therefore we have synthesized monodisperse Au@ZnO Janus particles by seed-mediated nucleation and growth whose ZnO domain was coated selectively with a thin SiO2 layer as a protection from the surrounding environment that imparts stability in aqueous media while the Au domain remained untouched. The thickness of the SiO2 layer could be precisely con-trolled. The SiO2 coating of the oxide domain allows biomolecule conjugation (e.g. antibodies, proteins) in a single step for con-verting the photoluminescent and photocatalytic active Janus nanoparticles into multifunctional efficient vehicles for cell target-ing. The SiO2-coated functionalized nanoparticles were stable in buffer solutions and other aqueous systems. Biocompatibility and potential biomedical applications of the Au@ZnO@SiO2 Janus particles were assayed by a cell viability analysis by co-incubating the Au@ZnO@SiO2 Janus particles with epithelia cells and compared to those of uncoated ZnO.
    Journal of Materials Chemistry B 01/2015; DOI:10.1039/C4TB02017K · 4.73 Impact Factor
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    ABSTRACT: Based on recent developments regarding the synthesis and design of Janus nanoparticles, they have attracted increased scientific interest due to their outstanding properties. There are several combinations of multicomponent hetero-nanostructures including either purely organic or inorganic, as well as composite organic–inorganic compounds. Janus particles are interconnected by solid state interfaces and, therefore, are distinguished by two physically or chemically distinct surfaces. They may be, for instance, hydrophilic on one side and hydrophobic on the other, thus, creating giant amphiphiles revealing the endeavor of self-assembly. Novel optical, electronic, magnetic, and superficial properties emerge in inorganic Janus particles from their dimensions and unique morphology at the nanoscale. As a result, inorganic Janus nanoparticles are highly versatile nanomaterials with great potential in different scientific and technological fields. In this paper, we highlight some advances in the synthesis of inorganic Janus nanoparticles, focusing on the heterogeneous nucleation technique and characteristics of the resulting high quality nanoparticles. The properties emphasized in this review range from the monodispersity and size-tunability and, therefore, precise control over size-dependent features, to the biomedical application as theranostic agents. Hence, we show their optical properties based on plasmonic resonance, the two-photon activity, the magnetic properties, as well as their biocompatibility and interaction with human blood serum.
    Beilstein Journal of Nanotechnology 12/2014; 5:2346. DOI:10.3762/bjnano.5.244 · 2.67 Impact Factor
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    ABSTRACT: Amine-functional poly(ethylene glycol) (PEG) copolymers have been prepared that exhibit thermo- and pH- responsive behavior in aqueous solution. Three novel tertiary di(n-alkyl)glycidylamine monomers have been introduced for anionic ring-opening copolymerization (AROcP) with ethylene oxide (EO): N,N-di(n-butyl)glycidylamine (DButGA), N,N-di(n-hexyl)glycidylamine (DHexGA), and N,N-di(n-octyl)glycidylamine (DOctGA). Via controlled AROcP we synthesized well-defined (Mw/Mn = 1.05–1.14), water-soluble block- and gradient-type PEG copolymers, containing up to 25 mol % of the respective dialkylglycidylamine comonomer. Molecular weights ranged from 4900 to 12 000 g mol–1. Detailed in-situ 1H NMR kinetics and 13C triad analyses elucidate the microstructures of the copolymers and the relative reactivity of the novel comonomers. Notably, the n-alkyl chain length had no significant influence on the relative reactivity of the glycidylamine comonomers. Calculated reactivity ratios ranged from rEO = 1.84, rDButGA = 0.49 to rEO = 1.78, rDOctGA = 0.42, manifesting the formation of gradient copolymers. Thermo- and pH-responsive properties of these copolymers are precisely tunable by the comonomer ratio, and cloud points in aqueous solution can be adjusted between 21 and 93 °C. Electron paramagnetic resonance (EPR) spectroscopic studies with TEMPO as a spin probe were conducted to elucidate host–guest interactions of the copolymers. Unexpectedly, the n-alkyl chain length of the different glycidylamine comonomers only influences the inverse phase transition of the gradient copolymers, but not of the block copolymers on the nanoscale. Self-assembly of the block- and gradient-type copolymers in aqueous alkaline solution by both static and dynamic light scattering has also been investigated after confirming the existence of pure unimers in methanol.
    Macromolecules 11/2014; 47(22):7679-7690. DOI:10.1021/ma501367b · 5.80 Impact Factor
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    ABSTRACT: A series of well-defined polypeptide-polypeptoid block copolymers based on the body's own amino acids sarcosine and lysine are prepared by ring opening polymerization of N-carboxyanhydrides. Block lengths were varied between 200-300 for the shielding polysarcosine block and 20-70 for the complexing polylysine block. Dispersity indexes ranged from 1.05 to 1.18. Polylysine is polymerized with benzyloxycarbonyl as well as trifluoroacetyl protecting groups at the ϵ-amine group and optimized deprotection protocols for both groups are reported. The obtained block ionomers are used to complex pDNA resulting in the formation of polyplexes (PeptoPlexes). The PeptoPlexes can be successfully applied in the transfection of HEK 293T cells and are able to transfect up to 50% of cells in vitro (FACS assay), while causing no detectable toxicity in an Annexin V assay. These findings are a first indication that PeptoPlexes may be a suitable alternative to PEG based non-viral transfection systems.
    Macromolecular Bioscience 10/2014; 14(10). DOI:10.1002/mabi.201400167 · 3.85 Impact Factor
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    ABSTRACT: Front Cover: A series of well-defined polypeptide-polypeptoid block copolymers based on the body's own amino acids sarcosine and lysine are prepared by K. Fischer, M. Bros, M. Barz, and co-workers on page 1380 by ring opening polymerization of N-carboxyanhydrides. The obtained block ionomers are used to complex pDNA resulting in the formation of polyplexes (PeptoPlexes). The PeptoPlexes can be successfully applied in the transfection of HEK293 T cells and are able to transfect up to 50% of cells in vitro (FACS assay), while causing no detectable toxicity in an Annexin V assay. These findings are a first indication that PeptoPlexes may be a suitable alternative to PEG based non-viral transfection systems.
    Macromolecular Bioscience 10/2014; 14(10):1355. DOI:10.1002/mabi.201470035 · 3.85 Impact Factor
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    ABSTRACT: To achieve specific cell targeting by various receptors for oligosaccharides or antibodies, a carrier must not be taken up by any of the very many different cells and needs functional groups prone to clean conjugation chemistry to derive well-defined structures with a high biological specificity. A polymeric nanocarrier is presented that consists of a cylindrical brush polymer with poly-2-oxazoline side chains carrying an azide functional group on each of the many side chain ends. After click conjugation of dye and an anti-DEC205 antibody to the periphery of the cylindrical brush polymer, antibody-mediated specific binding and uptake into DEC205+-positive mouse bone marrow-derived dendritic cells (BMDC) was observed, whereas binding and uptake by DEC205− negative BMDC and non-DC was essentially absent. Additional conjugation of an antigen peptide yielded a multifunctional polymer structure with a much stronger antigen-specific T-cell stimulatory capacity of pretreated BMDC than application of antigen or polymer–antigen conjugate.
    Chemistry - A European Journal 08/2014; 20(39). DOI:10.1002/chem.201403942 · 5.73 Impact Factor
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    ABSTRACT: Multifunctional linear (CA-linPG) and hyperbranched polyglycerols (CA-hbPG) bearing a single catechol unit were synthesized by use of an acetonide-protected catechol initiator for the anionic polymerization of ethoxyethyl glycidyl ether (EEGE) and glycidol, respectively. A key feature for the synthesis of the hyperbranched structures was a selective, partial acetal deprotection step. The single catechol unit among a large number of aliphatic 1,2- and 1,3-diol moieties (i.e., the “needle in the haystack”) in both linear and hyperbranched polyglycerols permits dispersion of transition metal oxide nanoparticles in brine, as demonstrated for manganese oxide (MnO) nanoparticles. Molecular weights of the single catechol bearing PGs ranged from 950 to 2350 g·mol-1 for CA-linPG and from 3750 to 5750 g·mol-1 for CA-hbPG with narrow and monomodal molecular weight distributions (Mw/Mn < 1.23 for linPG and Mw/Mn = 1.22-1.48 for hbPG). Both C-linPGs and C-hbPGs are suitable hydrophilic capping agents to generate highly hydroxyl-functional nanoparticles with hydrophilic PG shell. The PG content of the polymer-coated MnO nanoparticles (diameter 17 nm) was in the range 21-54 wt %, as determined via TGA. The MnO nanoparticles with a hydrophilic, multifunctional polyglycerol shell may represent a promising alternative to iron oxide or gadolinium contrast agents for MRI.
    Macromolecules 07/2014; 47(14):4557-4566. DOI:10.1021/ma5003672 · 5.80 Impact Factor
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    ABSTRACT: For systemic siRNA delivery applications, well-defined drug carriers are required that guarantee stability for both carrier and cargo. Among various concepts progressing in market or final development, cationic nanohydrogel particles may serve as novel transport media especially designed for siRNA-in vivo experiments. In this work, the interaction of nanohydrogel particles with proteins and serum components was studied via dynamic light scattering in human blood serum as novel screening method prior to applications in vivo. The formation of larger aggregates mostly caused by charge interaction with albumin could be suppressed by nanogel loading with siRNA affording a neutral zeta potential for the complex. Preliminary in vivo studies confirmed the results inside the light-scattering cuvette. Although both carrier and cargo may have limited stability on their own under physiological relevant conditions, they can form safe and stable complexes at a charge neutralized ratio and thus making them applicable to systemic siRNA delivery.
    Biomacromolecules 04/2014; 15(4). DOI:10.1021/bm500199h · 5.75 Impact Factor
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    ABSTRACT: Monodisperse multifunctional and non-toxic Au@MnO nano-hetero-particles with different sizes and morphologies were prepared by a seed-mediated nucleation and growth technique with precise control over domain sizes, surface functionalization, and dye labeling. The metal oxide domain could be coated selectively with a thin silica layer leaving the metal domain untouched. In particular, size and morphology of the individual (metal and metal oxide) domains could be controlled by adjustment of the synthetic parameters. The SiO2 coating of the oxide domain allows biomolecule conjugation (e.g. antibodies, proteins) in a single step for converting the photoluminescent and magnetic Janus nanoparticles into multifunctional efficient vehicles for theranostics. The Au@MnO@SiO2 heterodimers were characterized using high-resolution transmission electron microscopy (HR-) TEM, powder x-ray diffraction (PXRD), optical (UV-VIS) spectroscopy, confocal laser fluorescence scanning microscopy (CLSM) and dynamic light scattering (DLS). The functionalized nanoparticles were stable in buffer solution or serum showing no indication of aggregation. Biocompatibility and potential biomedical applications of the Au@MnO@SiO2 Janus particles were assayed by a cell viability analysis by co-incubating the Au@MnO@SiO2 Janus particles with Caki 1 and HeLa cells. Time-resolved fluorescence spectroscopy in combination with CLSM revealed the silica-coated Au@MnO@SiO2 heterodimers to be highly two-photon active; no indication for an electronic interaction between the dye molecules incorporated in the silica shell surrounding the MnO domains and the attached Au domains was found; fluorescence quenching was observed when dye molecules were bound directly to the Au domains.
    Journal of the American Chemical Society 01/2014; 136(6). DOI:10.1021/ja410787u · 12.11 Impact Factor
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    ABSTRACT: Herein, a new method for the realization of a thin and homogenous carbonaceous particle coating, made by carbonizing RAFT polymerization derived block copolymers anchored on anatase TiO2 nanorods, is presented. These block copolymers consist of a short anchor block (based on dopamine) and a long, easily graphitizable block of polyacrylonitrile. The grafting of such block copolymers to TiO2 nanorods creates a polymer shell, which can be visualized by atomic force microscopy (AFM). Thermal treatment at 700 °C converts the polyacrylonitrile block to partially graphitic structures (as determined by Raman spectroscopy), establishing a thin carbon coating (as determined by transmission electron microscopy, TEM, analysis). The carbon-coated TiO2 nanorods show improved electrochemical performance in terms of achievable specific capacity and, particularly, long-term cycling stability by reducing the average capacity fading per cycle from 0.252 mAh g(-1) to only 0.075 mAh g(-1) .
    Macromolecular Rapid Communications 11/2013; 34(21). DOI:10.1002/marc.201300531 · 4.94 Impact Factor
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    ABSTRACT: Poly(ε-N-methacryloyl-l-lysine) (PMALys) was synthesized by free radical polymerization yielding a zwitterionic polymer with Mw = 721 000 g mol–1. The polymer dissolves in pure water as well as in aqueous salt solution up to 5 M NaClO4 and over wide range of pH values (1.3 ≤ pH ≤ 12.7) as single chains without any sign for aggregate formation. The zwitterionic polymer shows an expanded random coil structure at and close to isoelectric conditions and further expands upon addition of acid and base, respectively. The polymer fulfills four major prerequisites for a promising nano carrier in potential biomedical applications: (1) It is biocompatible, indicated by a low cytotoxicity. (2) It does not aggregate in concentrated human blood serum solution. (3) The amino groups in the polyzwitterion may be utilized for conjugations as demonstrated by labeling reactions with AlexaFluor488. (4) Cell uptake experiments revealed little uptake in bone marrow dendritic cells, i.e., little unspecific uptake, which is mandatory for a successful specific targeting of cells. Finally, upon addition of Zn2+ ions the polyzwitterions may be converted into polycations which are demonstrated to form complexes with DNA. Such complexes may be advantageous for application in gene transfection studies.
    Macromolecules 10/2013; 46(21):8519-8527. DOI:10.1021/ma401549c · 5.80 Impact Factor
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    ABSTRACT: Supramolecular assembly: Spherical and stable hybrid assemblies based on a cationic polymer with spermine side chains and an anionic Gd(3+) -containing polyoxometalate cluster (GdW) are prepared by electrostatic interaction. The T1 -weighted MRI performance of GdW is enhanced about three times in the assemblies; meanwhile, the assemblies show good biocompatibility, which enables them to be promising candidates for MRI contrast agents.
    Chemistry - A European Journal 09/2013; 19(40). DOI:10.1002/chem.201302618 · 5.73 Impact Factor
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    ABSTRACT: Immediately after administration, polymer therapeutics are exposed to complex biological media like blood which may influence and alter their physicochemical properties due to interactions with proteins or serum components. Among such interactions those leading to larger sized aggregates can be sensitively detected by dynamic light scattering (DLS) as a pre in vivo screening method. Random copolymers from N-(2-hydroxypropyl)methacrylamide and lauryl methacrylate p(HPMA-co-LMA) and copolymers loaded with the model drug domperidone were characterized by DLS in isotonic salt solution and in blood serum. The bare amphiphilic copolymer micelles (Rh = 30 nm in isotonic salt solution) formed large aggregates in serum of over 100 nm radius which were shown to originate from interactions with very low density lipoproteins (VLDLs). Encapsulation of the hydrophobic drug domperidone resulted, at first, in drug-copolymer formulations with larger hydrodynamic radii (39 nm < Rh < 49 nm) which, however, did not induce aggregate formation in human serum. Since p(HPMA-co-LMA) copolymers were demonstrated to have a high potential for drug delivery into the brain, the knowledge of serum-copolymer interactions provides a better understanding of their function in the biological context.
    Molecular Pharmaceutics 09/2013; 10(10). DOI:10.1021/mp400254b · 4.38 Impact Factor
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    ABSTRACT: Monodisperse high molar mass elastin-like polypeptide macromonomers comprising 20 pentasequences (M = 8332 g/mol) were radically polymerized to high degrees of polymerization Pw = 590. Polymerization was conducted in water well above the lower phase transition temperature, i.e., in the phase separated regime. The resulting polymers adopt a cylindrical shape as demonstrated by AFM pictures of solutions spin-cast on mica. The directional persistence of the cylindrical brushes was determined by static light scattering to Kuhn statistical segments lengths lk = 120 nm at 5 mM aqueous NaCl solution which decreased to lk = 54 nm at 0.65 M NaCl. Upon polymerization the phase transition temperature drops significantly and the transition interval becomes sharper. The change of the hydrodynamic radius of the cylindrical brushes was monitored by dynamic light scattering as a function of temperature and revealed a continuous decrease from 20 to 36 °C, above of which aggregates of several hundred nm in size start to form prior to phase separation.
    Macromolecules 06/2013; 46(12):4966–4971. DOI:10.1021/ma400917t · 5.80 Impact Factor
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  • Jasmin Bühler · Sandra Muth · Karl Fischer · Manfred Schmidt ·
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    ABSTRACT: A high-molar-mass cylindrical brush polymer with a main chain degree of polymerization of P(w) = 1047 is synthesized by free-radical polymerization of a poly-2-isopropyloxazoline macromonomer with P(n) = 28. The polymerization is conducted above the lower phase transition temperature of the macromonomer, i.e., in the phase-separated regime, which provides a sufficiently concentrated macromonomer phase mandatory to obtain high-molar-mass cylindrical brushes. Upon heating to the phase transition temperature, the hydrodynamic radius is observed to shrink from 34 to 27 nm. Further increase in temperature resulted in aggregated chains which were observed to coexist with single chains until eventually only aggregates of μm size were detectable.
    Macromolecular Rapid Communications 04/2013; 34(7). DOI:10.1002/marc.201200784 · 4.94 Impact Factor
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    ABSTRACT: Scale formation, the deposition of certain minerals such as CaCO3, MgCO3 and CaSO4 x 2H2O in industrial facilities and household devices, leads to reduced efficiency or severe damages. Therefore, incrustation is a major problem in everyday life. In recent years, double hydrophilic block copolymers (DHBC) have been in the focus of interest in academia with regards to their anti-scaling potential. In this work, we synthesized well-defined block-like PAA-PAMPS copolymers consisting of acrylic acid (AA) and 2-acrylamido-2-methyl-propane sulfonate (AMPS) units in a one-step reaction by RAFT polymerization. The derived copolymers had dispersities of 1.3 and below. The copolymers have then been investigated in detail regarding their impact on the different stages of the crystallization process of CaCO3. Ca2+ complexation, the first step of a precipitation process, and polyelectrolyte stability in aqueous solution have been investigated by potentiometric measurements, isothermal titration calorimetry (ITC) and dynamic light scattering (DLS). A weak Ca2+ induced copolymer aggregation without concomitant precipitation was observed. Nucleation, early particle growth and colloidal stability have been monitored in situ with DLS. The copolymers retard or even completely suppress nucleation, most probably by complexation of solution aggregates. In addition, they stabilize existing CaCO3 particles in the nanometer regime. In situ AFM was used as a tool to verify the coordination of the copolymer to the calcite (104) crystal surface and to estimate its potential as a growth inhibitor in a supersaturated CaCO3 environment. All investigated copolymers instantly stopped further crystal growth. The carboxylate richest copolymer as the most promising anti-scaling candidate proved its enormous potential in scale inhibition as well in an industrial-filming test (Fresenius standard method).
    Langmuir 02/2013; 29(9). DOI:10.1021/la4000044 · 4.46 Impact Factor
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    ABSTRACT: Cylindrical brush polymers with poly-L-lysine side chains were prepared by grafting lysine NCA from a macroinitiator via living ring-opening polymerization. The main chain degree of polymerization of the methacrylate main chain was P-w = 870, the side chains consisted of 25 and 55 lysine repeat units, respectively. Upon deprotection, the cylindrical brush polymers in 0.005 M NaBr exhibited an almost rodlike conformation with a Kuhn statistical segment length of several hundred nanometers. Cryo-TEM as well as AFM in aqueous solution clearly demonstrated pronounced undulations along the main chain at low ionic strength which could not be detected at higher salt concentrations. With increasing concentration of NaClO4 the PLL side chains underwent a coil-to-helix transition as revealed by CD measurements. The effect of the side chain coil-to-helix transition on the main chain stiffness could not be followed by light scattering due to intramolecular attraction ("folding") of the cylindrical brushes at high salt concentration, which is somewhat more pronounced for the helical as compared to the coiled PLL side chain conformation. Comparison with linear PLL revealed the coil-to-helix transition to be hardly affected by the high grafting density of the PLL side chains in the cylindrical brush structures.
    Macromolecules 06/2012; 45(12):5167-5175. DOI:10.1021/ma300377v · 5.80 Impact Factor

Publication Stats

2k Citations
394.41 Total Impact Points


  • 1996-2015
    • Johannes Gutenberg-Universität Mainz
      • Institute of Physical Chemistry
      Mayence, Rheinland-Pfalz, Germany
  • 1992-1995
    • University of Bayreuth
      • • Bayreuth Institute of Macromolecular Research (BIMF)
      • • Chair of Macromolecular Chemistry II
      Bayreuth, Bavaria, Germany