TY - JOUR A1 - Herfurth, Christoph A1 - Laschewsky, Andre A1 - Noirez, Laurence A1 - von Lospichl, Benjamin A1 - Gradzielski, Michael T1 - Thermoresponsive (star) block copolymers from one-pot sequential RAFT polymerizations and their self-assembly in aqueous solution JF - Polymer : the international journal for the science and technology of polymers N2 - A series of hydrophobically end-capped linear triblock copolymers as well as of three-arm and four-arm star block copolymers was synthesized in a one-pot procedure from N,N-dimethylacrylamide (DMA) and N, N-diethylacrylamide (DEA). The sequential reversible addition-fragmentation chain transfer (RAFT) polymerization of these monomers via the R-approach using bi-, tri- and tetrafunctional chain transfer agents (CrAs) bearing hydrophobic dodecyl moieties proceeded in a well-controlled manner up to almost quantitative conversion. Polymers with molar masses up to 150 kDa, narrow molar mass distribution (PDI <= 1.3) and high end group functionality were obtained, which are thermoresponsive in aqueous solution showing a LCST (lower critical solution temperature) transition. The temperature-dependent associative behavior of the polymers was examined using turbidimetry, static and dynamic light scattering (SLS, DLS), and small angle neutron scattering (SANS) for structural analysis. At 25 degrees C, the polymers form weak transient networks, and rather small hydrophobic domains are already present for polymer concentrations of 5 wt%. However, when heating above the LCST transition (35-40 degrees C) of the PDEA blocks, the enhanced formation of hydrophobic domains is observed by means of light and neutron scattering. These domains have a size of about 12-15 nm and must be effectively physically cross-linked as they induce high viscosity for the more concentrated samples. SANS shows that these domains are ordered as evidenced by the appearance of a correlation peak. The copolymer architecture affects in particular the extent of ordering as the four-arm star block copolymer shows much more repulsive interactions compared to the analogous copolymers with a lower number of arms. (C) 2016 Elsevier Ltd. All rights reserved. KW - RAFT polymerization KW - Block copolymers KW - Thermosensitivity KW - LCST KW - SANS KW - Light scattering Y1 - 2016 U6 - https://doi.org/10.1016/j.polymer.2016.09.089 SN - 0032-3861 SN - 1873-2291 VL - 107 SP - 422 EP - 433 PB - Elsevier CY - Oxford ER - TY - THES A1 - Hess, Andreas T1 - Synthese von funktionalisierbaren und abbaubaren Polymersystemen mit Disulfiden T1 - Synthesis of functionalizable and degradable polymer systems with disulfides N2 - Die vorliegende Arbeit beschäftigt sich mit der Synthese von Disulfiden, der Thiol-Disulfid Metathesereaktion als Möglichkeit, Polymere zu funktionalisieren, und der Synthese von Polydisulfiden. Im ersten Teil der Arbeit wird die Aminolyse von RAFT-Polymeren und die Abhängigkeit der Polymer-Polymer Disulfidbildung von der Molmasse untersucht. Dabei wurde durch die Aufnahme von Reaktionskinetiken mittels Gel-Permeations-Chromatographie (GPC) festgestellt, dass je länger die Polymerketten sind, desto weniger Disulfid Polymerkopplung tritt auf. RAFT-Polymere werden oft genutzt, um die RAFT-Polymer Endgruppe nach der Polymerisation zu modifizieren oder in einer chemischen Reaktion zu funktionalisieren. Hier kann die Aminolyse in Anwesenheit von kurzkettigen Disulfiden, wie zum Beispiel Cystin, durchgeführt werden, um die Bildung von Polymer-Polymer Disulfiden vollständig zu unterdrücken und ein endgruppenfunktionalisiertes Polymer zu erhalten. Bei dieser Reaktion greift das bei der Aminolyse entstehende Polymerthiolat die kurzkettigen Disulfide an, und es kommt zur Bildung von funktionalisierten Polymeren. Es wurde ein Polyethylenglykoldisulfid eingesetzt, um ein amphiphiles Blockcopolymer zu erhalten. Als RAFT-Polymer wurde Polystyrol (PS) verwendet, und es konnte die Bildung von Polystyrol-Polyethylenglykol Copolymeren nachgewiesen werden. Das amphiphile Polymer bildet im wässrigen Medium Vesikel. Die Oberfläche der Vesikel konnte mittels der Thiol-Disulfid Metathese umfunktionalisiert werden. Die Aminolyse von PS RAFT-Polymeren mit einem Polylaktiddisulfid oder einem Polybenzylglutamatdisulfid ergab Polystyrol-block-Polyester und Polystyrol-block-Polyaminosäuren Copolymere. Im zweiten Teil der Arbeit liegt der Fokus auf der Synthese von Polydisulfiden und ihren thermischen Eigenschaften. Es wurden verschiedene Alkyldithiole synthetisiert und mittels Wasserstoffperoxid und Triethylamin polymerisiert. Dabei konnte gezeigt werden, dass die Polymere teilkristallin sind und dass der Schmelzpunkt und die Kristallinität der Polymere mit steigender Alkylkettenlänge zwischen den Disulfidbindungen zunehmen. Die Möglichkeit einer Polymerkettenerweiterung nach der Polymerisation ist mit diesem System gegeben. Die Abbaubarkeit der Polydisulfide konnte durch den Einsatz von Thiolen im basischen Milieu gezeigt werden. N2 - This thesis deals with the synthesis of polymer disulfides, the thiol-disulfide metathesis reaction as a method for functionalization of polymers and the synthesis of polydisulfides. The first part covers the aminolysis of RAFT polymers and the molecular weight dependence of disulfide formation during the RAFT-end group removal. Kinetics of aminolysis reaction for different RAFT polymers with different molecular weight were analyzed by size-exclusion chromatography (SEC). The RAFT polymers tend to form less dimers with increasing molecular weight. It was tried to cleave the disulfide bonds between the polymers with thiols. When the aminolysis of RAFT polymers was performed in the presence of different disulfides, only functionalized polymers were obtained. The formation of polymer-polymer disulfide bond during the aminolysis was completely suppressed in the presence of low molecular weight disulfides. This functionalization of RAFT polymers is not limited to end groups but is also useful for the synthesis of block copolymers. An amphiphilic block copolymer containing polystyrene (PS) and polyethylene glycol (PEG) was produced from a PS RAFT polymer and a PEG disulfide. This PS-PEG block copolymer undergoes self assembly to form vesicular structures in water. The outer shell of these vesicles were modified by selective removal of the PEG polymers followed by attachment of Ellman’s reagent on the surface. When the aminolysis of polystyrene RAFT polymers was performed in the presence of polylactide disulfides or polybenzylglutamate disulfides, polystyrene-block-polyester and polystyrene-block-polyaminoacid copolymers were obtained. The second part of this thesis deals with the synthesis of polydisulfides and their thermal properties. Dithiols with different alkyl chain lengths were synthesized and polymerized to form polydisulfides. This polymerization is performed by using triethylamine and hydrogen peroxide. The triethylamine is used as base to deprotonate the thiol to form a thiolate ion which then is oxidized by hydrogen peroxide to a disulfide. The obtained polydisulfides are semicrystalline in nature. The crystallinity as well as the melting temperature of polydisulfides increases with increasing alkyl chain length. These polydisulfides are degradable under basic conditions. KW - RAFT-Polymerisation KW - Aminolyse KW - Funktionalisierung KW - Vesikel KW - Polydisulfide KW - RAFT polymerization KW - aminolysis KW - functionalization KW - vesicle KW - poly(disulfide)s Y1 - 2021 ER - TY - JOUR A1 - Kuroki, Agnes A1 - Tchoupa, Arnaud Kengmo A1 - Hartlieb, Matthias A1 - Peltier, Raoul A1 - Locock, Katherine E. S. A1 - Unnikrishnan, Meera A1 - Perrier, Sebastien T1 - Targeting intracellular, multi-drug resistant Staphylococcus aureus with guanidinium polymers by elucidating the structure-activity relationship JF - Biomaterials : biomaterials reviews online N2 - Intracellular persistence of bacteria represents a clinical challenge as bacteria can thrive in an environment protected from antibiotics and immune responses. Novel targeting strategies are critical in tackling antibiotic resistant infections. Synthetic antimicrobial peptides (SAMPs) are interesting candidates as they exhibit a very high antimicrobial activity. We first compared the activity of a library of ammonium and guanidinium polymers with different sequences (statistical, tetrablock and diblock) synthesized by RAFT polymerization against methicillin-resistant S. aureus (MRSA) and methicillin-sensitive strains (MSSA). As the guanidinium SAMPs were the most potent, they were used to treat intracellular S. aureus in keratinocytes. The diblock structure was the most active, reducing the amount of intracellular MSSA and MRSA by two-fold. We present here a potential treatment for intracellular, multi-drug resistant bacteria, using a simple and scalable strategy. KW - Antimicrobial KW - Intracellular bacteria KW - Block copolymers KW - RAFT polymerization Y1 - 2019 U6 - https://doi.org/10.1016/j.biomaterials.2019.119249 SN - 0142-9612 SN - 1878-5905 VL - 217 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Laroque, Sophie A1 - Reifarth, Martin A1 - Sperling, Marcel A1 - Kersting, Sebastian A1 - Kloepzig, Stefanie A1 - Budach, Patrick A1 - Hartlieb, Matthias A1 - Storsberg, Joachim T1 - Impact of multivalence and self-assembly in the design of polymeric antimicrobial peptide mimics JF - ACS applied materials & interfaces N2 - Antimicrobial resistance is an increasingly serious challenge for public health and could result in dramatic negative consequences for the health care sector during the next decades. To solve this problem, antibacterial materials that are unsusceptible toward the development of bacterial resistance are a promising branch of research. In this work, a new type of polymeric antimicrobial peptide mimic featuring a bottlebrush architecture is developed, using a combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and ring-opening metathesis polymerization (ROMP). This approach enables multivalent presentation of antimicrobial subunits resulting in improved bioactivity and an increased hemocompatibility, boosting the selectivity of these materials for bacterial cells. Direct probing of membrane integrity of treated bacteria revealed highly potent membrane disruption caused by bottlebrush copolymers. Multivalent bottlebrush copolymers clearly outperformed their linear equivalents regarding bioactivity and selectivity. The effect of segmentation of cationic and hydrophobic subunits within bottle brushes was probed using heterograft copolymers. These materials were found to self-assemble under physiological conditions, which reduced their antibacterial activity, highlighting the importance of precise structural control for such applications. To the best of our knowledge, this is the first example to demonstrate the positive impact of multivalence, generated by a bottlebrush topology in polymeric antimicrobial peptide mimics, making these polymers a highly promising material platform for the design of new bactericidal systems. KW - RAFT polymerization KW - ROMP KW - antimicrobial polymers KW - antimicrobial peptide KW - mimics KW - bottlebrush copolymers Y1 - 2020 U6 - https://doi.org/10.1021/acsami.0c05944 SN - 1944-8244 SN - 1944-8252 VL - 12 IS - 27 SP - 30052 EP - 30065 PB - American Chemical Society CY - Washington ER -