Cyclic and linear cationic polymers based on metathesis polymerization for antibacterial and antifungal Applications

Abstract

Cationic polymers have emerged as a significant class of materials in the fight against antimicrobial resistance. The macromolecular topology, polymer size, cationic and hydrophobic moieties and their distribution within these polymers, play crucial roles in determining their antimicrobial properties and selectivity. In this study, we report the synthesis of cyclic cationic polymers via the combination of ring-expansion metathesis polymerization (REMP) and click chemistry, using a single cyclic poly(norbornenyl azlactone) platform. Notably, this methodology, recently reported by our group, has also been successfully applied to producing glycopolymers with lectin-binding ability. Herein, we employ a double post-polymerization modification (PPM) of these scaffolds, with number-average degrees of polymerization (DP_n) of 25 and 100. The azlactone moiety undergoes click aminolysis using N-Boc-ethylenediamine (BEDA) as a cationic precursor and 10 % n-hexylamine or n-dodecylamine as lipophilic side chains, in a one-pot process followed by Boc deprotection. This approach enabled the synthesis of a library of six cyclic and six linear cationic polymer analogues, which were characterized in detail using size-exclusion chromatography (SEC), FT-IR, and ¹H NMR spectroscopy. The antibacterial and antifungal properties of these polymers were assessed against a panel of microbial pathogens, including Gram-positive bacteria (methicillin resistant S. aureus), Gram-negative bacteria (E. coli, K. pneumoniae, P. aeruginosa, A. baumannii), and fungi (C. albicans, C. auris, C. krusei, C. tropicalis, C. neoformans, C. deuterogattii, C. gattii). Their cell cytotoxicity against human red blood cells and mammalian HEK293 cells was also investigated.