New Generation of N-Chloramine/QAC Composite Biocides: Efficient Antimicrobial Agents To Target Antibiotic-Resistant Bacteria in the Presence of Organic Load

[Image: see text] We previously reported that covalently joining an amide-based N-chloramine with a quaternary ammonium compound (QAC) can yield a new composite biocide with faster inactivation of various bacteria. Importantly, the composite biocide was found to reduce the risk for potential bacterial resistance associated with QAC. However, similar to other N-chloramines and QACs, this high-performance composite biocide becomes less potent against pathogenic bacteria in the presence of high protein fluids. In this study, we substituted the amide-based N-chloramine moiety in the previously reported composite biocide with a secondary amine-based N-chloramine to improve the biocidal efficacy in biological fluids. The N–Cl bond in the synthesized tetramethylpiperidine-based composite biocides is more stable in a high protein medium (HPM) than that in the hydantoin (amide)-based composite biocides. The composite biocide, 2-[4-(1-chloro-2,2,6,6-tetramethyl-piperidin-4-yloxymethyl)-[1,2,3]triazol-1-yl]-ethyl-dodecyl-dimethyl-ammonium chloride (6a), showed the best antibacterial activity in both phosphate-buffered saline and HPM among various composite biocides and benzyldodecyldimethylammonium chloride used in this study.