Antimicrobial Poly(2‐methyloxazoline)s with Bioswitchable Activity through Satellite Group Modification

Abstract

Biocides are widely used for preventing the spread of microbial infections and fouling of materials. Since their use can build up microbial resistance and cause unpredictable long-term environmental problems, new biocidal agents are required. In this study, we demonstrate a concept in which an antimicrobial polymer is deactivated by the cleavage of a single group. Following the satellite group approach, a biocidal quaternary ammonium group was linked through a poly(2-methyloxazoline) to an ester satellite group. The polymer with an octyl-3-propionoate satellite group shows very good antimicrobial activity against Gram-positive bacterial strains. The biocidal polymer was also found to have low hemotoxicity, resulting in a high HC50 /MIC value of 120 for S. aureus. Cleaving the ester satellite group resulted in a 30-fold decrease in antimicrobial activity, proving the concept valid. The satellite group could also be cleaved by lipase showing that the antimicrobial activity of the new biocidal polymers is indeed bioswitchable.

Copolymers of acrylonitrile with quaternizable thiazole and triazole side-chain methacrylates as potent antimicrobial and hemocompatible systems

“…This result agrees well with recently reported examples showing that hydrophilicity diminishes hemotoxicity and then increases selectivity [64,66,[72][73][74][75][76][77]. However, there has to be a correct balance between the hydrophilic and hydrophobic segments, since it has been also reported that the increase on hydrophobicity can lead to lower hemocytotoxicity [78,79]. Additionally, no differences were found between mono and biscationic side-chain tails.…”

Amide side chain amphiphilic polymers disrupt surface established bacterial bio-films and protect mice from chronic Acinetobacter baumannii infection

“…Degradation or deactivation of the polymer after required therapeutic effect has been achieved is important to avoid the long-term environmental problems and to release in-active M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 5 degradation by-products. Tiller and co-workers reported antimicrobial polymers with degradable ester satellite group that possess bio-switchable activity [52]. We show that cyclization and optimum hydrophobicity of side chains in these amphiphilic polymers influence the selective toxicity to bacteria sparing the mammalian cells.…”

Controlling macromolecular structures towards effective antimicrobial polymers

“…8) [99]. Cationic ring-opening polymerization of 2-methyl-2-oxazoline was used to prepare the polymer while termination with the biocidal group N,N-dimethyldodecylamine introduced antimicrobial activity (Table 4C).…”