Spatial Evolution of Antimicrobial Metallopolymers toward the Main Chain Topology

Synthetic polymers and peptides with spatial control have emerged as effective molecular agents for addressing antimicrobial resistance (AMR). We report on one of the first kinds of studies on how spatial compositions in cationic metallopolymers can be tuned to control their antimicrobial efficacy. As a representative, the evolution of cobaltocenium cation from side chain to main chain has shown drastic impacts on polymer-cell interactions and consequential killing of microbes. A main-chain cobaltocenium polymer exhibited broad-spectrum activity against multidrug-resistant (MDR) bacteria, primarily targeting bacterial cell membranes and outer leaflets. The polymer also showed a strong efficacy in treating mature biofilms across multiple bacterial strains. Resistance development was evaluated over 20 passages, with no detectable resistance. Overall, these findings reveal spatial control of cationic centers in metallopolymers as a unique molecular platform for combating MDR pathogens and alleviating the AMR burden on global healthcare settings.