Shape Matters: Highly Selective Antimicrobial Bottle Brush Copolymers via a One-Pot RAFT Polymerization Approach

Abstract

The one-pot synthesis of antimicrobial bottle brush copolymers is presented. Reversible addition–fragmentation chain-transfer (RAFT) polymerization is used for the production of the polymeric backbone, as well as for the grafts, which were installed using a grafting-from approach. A combination of N-isopropyl acrylamide and a Boc-protected primary amine-containing acrylamide was used in different compositions. After deprotection, polymers featuring different charge densities were obtained in both linear and bottle brush topologies. Antimicrobial activity was tested against three clinically relevant bacterial strains, and growth inhibition was significantly increased for bottle brush copolymers. Blood compatibility investigations revealed strong hemagglutination for linear copolymers and pronounced hemolysis for bottle brush copolymers. However, one bottle brush copolymer with a 50% charge density revealed strong antibacterial activity and negligible in vitro blood toxicity (regarding hemolysis and hemagglutination tests) resulting in selectivity values as high as 320. Membrane models were used to probe the mechanism of shown polymers that was found to be based on membrane disruption. The trends from bioassays are accurately reflected in model systems indicating that differences in lipid composition might be responsible for selectivity. However, bottle brush copolymers were found to possess increased cytotoxicity against human embryonic kidney (HEK) cells compared with linear analogues. The introduced synthetic platform enables screening of further, previously inaccessible parameters associated with the bottle brush topology, paving the way to further improve their activity profiles.

Trendbericht: Makromolekulare Chemie 2023

“…41) Gleichsam untersuchten Hartlieb und Team die Struktur-Eigenschaftsbeziehungen antimikrobieller Polymerbürsten. 42) Ebenfalls antimikrobielle Eigenschaften wiesen die Polyethersulfonmembranen auf, die Börner und Mitarbeitende entworfen und mit Photosensibilisatoren ausgerüstet hatten. 43) Fortschritte in der Synthese biomedizinisch wirksamer Makromoleküle erzielten Hartmann, Snyder und Hoffmann: Ihnen gelang die Festphasensynthese von sulfatierten Glykomakromolekülen als Analoga für biologisch aktive sulfatierte Glykosaminoglykane.…”

Influence of Polymer Side Chain Size and Backbone Length on the Self‐Assembly of Supramolecular Polymer Bottlebrushes

“…Furthermore, establishing a robust supramolecular platform would allow a versatile variation of attached polymers, while the elongated shape of the SPBs remains unaffected. [65,66] Moreover, such a systematic study allows cross-correlations with other systems and might lead to more general understanding on the influence of the polymer architecture on the final morphology. [12,[67][68][69] In this study, we therefore attached polymers of different length and side chain size to the established benzene trisurea (BTU) and benzene tris(phenylalanine) (BTP, formerly also called benzene trispeptide) core motifs to provide fundamental structure-property relations between the sterical demand of the attached polymers and the preservation of fiber formation in these promising supramolecular building blocks.…”

Amphiphilic star copolymers composed of curcumin core for bacterial inactivation

“…and Laroque et al 25 . Bottlebrush copolymers have also demonstrated increased activity compared to that of the linear form 26–28 …”

“…Even less employed, star polymers may present extended antimicrobial activity compared with their linear counterparts, 23 as demonstrated by Lam et al 24 and Laroque et al 25 Bottlebrush copolymers have also demonstrated increased activity compared to that of the linear form. [26][27][28] Star-shaped polymers prepared by reversible deactivation radical polymerization techniques are typically achieved using the core-first or arm-first methods. 29 Core-first methods use a multifunctional core from which the linear arms will grow, whereas by the arm-first method, the linear arms are obtained in the first step and then a bifunctional monomer, a crosslinker, is used to react with the linear chains and subsequently with other crosslinker molecules, resulting in a spherical polymeric topology.…”