(571b) Rational Design of Antimicrobial Polycarbonates

Biodegradable antimicrobial polymers are a promising solution for combating drug resistant microbes. Unlike many small molecule antibiotics which work on the inner machinery of the bacteria, these macromolecules kill microbes through physical disruption of the cell wall. When designing these materials, the balance between cationic charge and hydrophobicity significantly affects the antimicrobial activity and selectivity towards microbes over mammalian cells. For bacterial cell lysis, current mechanistic understanding suggests the cationic portion of the antimicrobial polymer associates with the negatively charged microbial membrane to form an initial association. Once in close proximity, the hydrophobic portion of the antimicrobial polymer inserts into the bacterial lipid bilayer, causing membrane disruption and eventual lyses.  Considerable work has been performed on the variance of charge and hydrophobicity, but far less has been done on investigating the effect of where the cationic and hydrophobic moieties are located on the molecule. Herein, we will discuss rational antimicrobial polymer design to obtain active and selective antimicrobial polymers using a model polycarbonate platform.