Ring-opening metathesis polymerization of N -methylpyridinium-fused norbornenes to access antibacterial main-chain cationic polymers

Abstract

Cationic polymers have been identified as a promising type of antibacterial molecules, whose bioactivity can be tuned through structural modulation. Recent studies suggest that the placement of the cationic groups close to the core of the polymeric architecture rather than on appended side chains might improve both their bioactivity and selectivity for bacterial cells over mammalian cells. However, antibacterial main-chain cationic polymers are typically synthesized via polycondensations, which do not afford precise and uniform molecular design. Therefore, accessing main-chain cationic polymers with high degrees of molecular tunability hinges upon the development of controlled polymerizations tolerating cationic motifs (or cation progenitors) near the propagating species. Herein, we report the synthesis and ring-opening metathesis polymerization (ROMP) of N -methylpyridinium-fused norbornene monomers. The identification of reaction conditions leading to a well-controlled ROMP enabled structural diversification of the main-chain cationic polymers and a study of their bioactivity. This family of polyelectrolytes was found to be active against both Gram-negative ( Escherichia coli ) and Gram-positive (Methicillin-resistant Staphylococcus aureus ) bacteria with minimal inhibitory concentrations as low as 25 µg/mL. Additionally, the molar mass of the polymers was found to impact their hemolytic activity with cationic polymers of smaller degrees of polymerization showing increased selectivity for bacteria over human red blood cells.

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“…For instance, Hancock SN et al conducted a study wherein they synthesized novel cationic polymers through controlled ring-opening metathesis polymerization of N-methylpyridinium-fused norbornenes. These polymers exhibited selective activity against both Gram-positive and Gram-negative bacteria, while sparing human red blood cells [ 7 ]. Furthermore, research has explored the utility of antimicrobial polymers such as chitosan [ 8 , 9 ] and polyethyleneimine [ 10 ], demonstrating promising outcomes in rupturing bacterial cell membranes, resulting in bacterial demise.…”