Antimicrobial Polymer with Enhanced Activity and Reduced Toxicity upon Grafting to Chitosan Oligosaccharide

The aim of this work was to develop a novel, nontoxic, bioactive antimicrobial material based on a natural polymer, chitosan oligosaccharides (COS), a natural pyrone compound, kojic acid (KA), and piperazine. The COS-based polymer (COS-O-MB) has been synthesized by selective partial alkylation reaction to graft kojic acid, KA, and piperazine onto the COS molecular chain. Then, physicochemical properties and bioactivity of the COS-O-MBs were evaluated and it was characterized by FT-IR, NMR spectroscopy, Mw, PID, antimicrobial activity, hemolysis assay, biocompatibility, animal toxicity, and antimicrobial action mode studies. The results revealed that the alkylation reaction took place at the C-6 position of COS, and the as-prepared COS-O-MB significantly enhanced the antimicrobial activity and biocompatibility and reduced the hemolytic activity in vitro in comparison with that of the free COS and KA. Meanwhile, the antimicrobial action mode studies proved that COS-O-MB can pass through the anionic microbial membrane, destroy the cytomembrane integrity, and potentially affect protein denaturation, demonstrating that exposure to COS-O-MB results in the death of microbial cells. But importantly, COS-O-MB is not toxic to human cells. Hence, low hemolytic activity to human red blood cells, and nontoxic nature to female mice of SLAC KM strain, made this novel polymer material a promising and effective compound for food and pharmaceutical industries.