Conversion of oligo(ethyleneglycol)s into non-toxic highly selective biocompatible poly(ethyleneglycol)s: synthesis, antimicrobial and antibiofilm activity†

Abstract

Designing non-toxic, non-hemolytic, selective antimicrobials remains an important and challenging research problem. Herein, we report an affordable synthetic route to prepare a series of ten multifunctional polyethylene glycols (PEGs) via a cascade reaction approach involving aza-Michael polyaddition followed by post-polymerization modifications using triazolinedione-based click reactions. All polymers are characterized by NMR, IR, SEC, DSC and TG analyses. Antimicrobial and hemolytic studies reveal that structure plays a pivotal role in tuning the antimicrobial efficacy and selectivity (HC/MIC) of the functional PEGs. The selectivity (HC/MIC) reported for the best prototype (InPEG₇₀₀-C₁₂-TAD) is 129, 33 and 39 against P. aeruginosa, E. coli and S. aureus, respectively. Additionally, all the polymers are non-cytotoxic, as revealed by the MTT assay, and exhibit excellent antibiofilm activity.