Biodegradable polycaprolactone metallopolymer–antibiotic bioconjugates containing phenylboronic acid and cobaltocenium for antimicrobial application

Abstract

This paper reports antimicrobial metallopolymers containing biodegradable polycaprolactone as the backbone with boronic acid and cobaltocenium as the side chain. While boronic acid promotes interactions with bacterial cells via boronolectin with lipopolysaccharides, cationic cobaltocenium facilitates the unique complexation with anionic β-lactam antibiotics. The synergistic interactions in these metallopolymer–antibiotic bioconjugates were evidenced by re-sensitized efficacy of penicillin-G against four different Gram-negative bacteria (E. coli, P. vulgaris, P. aeruginosa and K. pneumoniae). The degradability of the polyester backbone was validated through tests under physiological pH (7.4) and acidic pH (5.5) or under enzymatic conditions. These metallopolymers exhibited time-dependent uptake and reduction of cobalt metals in different organs of mice via in vivo absorption, distribution, metabolism, and excretion (ADME) tests.