Antimicrobial Polycarbonates: Investigating the Impact of Nitrogen-Containing Heterocycles as Quaternizing Agents

Abstract

Synthetic polymeric antimicrobials have received enormous attention recently on the back of increasing multidrug-resistance microbes. While conventional small molecular antibiotics act on specific targets to inhibit microbe activities, macromolecular antimicrobials physically destroy cell membranes of the organism rendering them ineffective; the mechanism of the latter aids in the prevention of developing drug-resistance microbes. In this investigation, we report on the synthesis of biodegradable cationic polycarbonates containing propyl and hexyl side chains quaternized with various nitrogen-containing heterocycles, such as imidazoles and pyridines, and their <i>in vitro</i> antimicrobial application. These polymers demonstrate a wide spectrum of activity (using minimum inhibitory concentrations analysis) against <i>Staphylococcus aureus</i> (Gram-positive), <i>Escherichia coli</i> (Gram-negative), <i>Pseudomonas aeruginosa</i> (Gram-negative), and <i>Candida albicans</i> (fungus). Hemolysis experiments also show high selectivity toward the tested microbes over mammalian (rat) red blood cells (<i>r</i>RBCs). In particular, some of the polymers can achieve >250 times selectivity of <i>S. aureus</i> over <i>r</i>RBCs. In addition, the polymers function via a membrane-lytic mechanism; hence, they are less likely to develop drug resistance. All these properties make them ideal candidates as antimicrobial agents