Synthesis of Gemini-Quaternary Ammonium N-Chloramine Biocides for Antibacterial Applications

A series of Gemini-quaternary ammonium (QA) N-chloramine biocides N,N-bis(3-(3-chloro-4,4-dimethyl-2,5-di-oxoimidazolidin1-yl)propyl)-N,N, N,N-tetramethylbutane-1,4-diaminium chloride (6)similar to N,N-bis(3-(3-chloro-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)propyl)-N,N, N,N-tetramethyldecane-1,10-diaminiumchloride (9) with varied spacers were synthesized via ploy-step strategy started from commercial 5,5-dimethylhydantoin. The structures of precursors and corresponding N-chloramines were characterized by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectra (HRMS). Antibacterial activity of N-chloramines was preliminarily tested against E. coli (ATCC 25922) and S. aureus (ATCC 25923) using previous Gemini-QA N-chloramine 5 as control. Antibacterial data showed that antibacterial potency of 5 similar to 9 declined first and then increased as the spacer length increased. Specifically, 9 (with spacer of C10H20) demonstrated the towering antibacterial capability, superior to 5 similar to 6 that exerted noticeable biocidal team effort. The greatly enhanced efficacy of 9 was probably caused by its preferable hydrophilic-lipophilic balance. It means that spacer length determines team effort biocidal and hydrophilic-lipophilic characteristic greatly contributes efficient contact killing. This study provides a series of efficacious cationic N-chloramine disinfectants, and also offers a vital reference for developing new N-chloramine antimicrobials with even higher efficacy.