The prevalence of drug-resistant bacterial infections is an eminent health issue facing society today.This surge in tolerance has curbed our arsenal of effective antimicrobials, causing a precarious situation that has been exacerbated by the declining number of new antibiotics introduced in recent years. There is thus a dire need for novel classes of antimicrobials to be developed, particularly with alternative modes of action that exhibit reduced propensity towards resistance development.To this end, biodegradable antimicrobial polymers have recently emerged as a promising solution for combating drug-resistant pathogens while being tolerant towards resistance development due to the physical nature of its antimicrobial mechanism. It has been widely established that the balance between cationic charge and hydrophobicity (i.e. amphiphilic balance) is pertinent in influencing the biological properties of antimicrobial polymers. While considerable design efforts has been directed towards tuning the amphiphilic balance via copolymerization of disparate cationic and hydrophobic monomers (i.e. 'segregated monomer' approach), the 'same centered' design (i.e. hydrophobic moiety directly conjugated to cationic component) has insofar been warranted insufficient attention. We posit that such a design strategy would allow for a more prudent control of the polymer's global amphiphilicity and effectively delineate pivotal structural determinants that might have a significant bearing on its activity and selectivity. Herein, using a model polycarbonate platform, we will discuss a rational 'same centered' design strategy to develop potent and highly selective macromolecular antimicrobials. 

Rational "same centered" design strategy for the development of potent and highly selective antimicrobial polycarbonates

248th National Meeting (2014)

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