Photo-iniferter (PI)-RAFT polymerization, the direct activation of chain transfer agents via light, is a fascinating polymerization technique, as it overcomes some restriction of conventional RAFT polymerization. As such, we elucidated...
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.
The one-pot synthesis of antimicrobial bottle brush copolymers is presented. RAFT polymerization is used for production of the polymeric backbone, as well as for the grafts, which were installed using a grafting from approach. A combination of N-iso propyl acrylamide and a Boc protected primary amine-containing acrylamide was used in different composition. After deprotection polymers featuring different charge densities were obtained in both, linear and bottle brush topology. Antimicrobial activity was tested against three clinically relevant bacteria strains and growth inhibition was significantly increased in 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 strong antibacterial activity and negligible blood toxicity resulting in selectivity values as high as 320. Membrane models were used to probe the mechanism of shown polymers, which was found to be based on membrane disruption. The trends from biology are accurately reflected in model systems indicating that differences in lipid composition are responsible for selectivity. However, bottle brush copolymers were found to possess increased cytotoxicity against HEK cells when compared with linear analogues. The introduced synthetic platform enables screening of further parameters associated to bottle brush copolymers, which might lead to even better activity profiles.
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