以5,5-二甲基海因为原料, 通过多步合成策略制备了一系列不同长度spacer的双子(Gemini)季铵盐氯胺抗菌剂N,N-双(3-(3-氯-4,4-二甲基-2,5-二氧亚基咪唑烷-1-基)丙基)-N,N,N,N-四甲基丁烷-1,4-二铵氯化物(6)~N,N-双(3-(3-氯-4,4-二甲基-2,5-二氧亚基咪唑烷-1-基)丙基)-N,N,N,N-四甲基癸烷-1,10-二铵氯化物(9), 采用核磁共振波谱(NMR)和高分辨质谱(HRMS)表征了前体和氯胺结构. 以E. coli (ATCC 25922)和S. aureus (ATCC 25923)为模式菌株, 以已报道的Gemini-季铵盐氯胺5为对照, 初步测试了氯胺6~9抗菌活性. 抗菌数据表明, 5~9抗菌活性随结构中spacer增大呈现了先减弱后增强的趋势, 其中spacer为C₁₀H₂₀的氯胺9抗菌活性达到了最佳, 明显优于具有“团队”抗菌效应的5~6, 这可能是9达到了分子触杀所需最佳的亲疏水平衡状态所致. 表明spacer大小决定了“团队”协同抗菌作用的强弱, 且双亲氯胺亲疏水状态对分子触杀贡献极大. 合成了一系列高效阳离子型氯胺抗菌剂, 为今后更高效氯胺抗菌剂研发提供重要参考.

A series of Gemini-quaternary ammonium (QA) N-chloramine biocides N,N-bis(3-(3-chloro-4,4-dimethyl-2,5-di- oxoimidazolidin-1-yl)propyl)-N,N,N,N-tetramethylbutane-1,4-diaminium chloride (6)~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 5~9 declined first and then increased as the spacer length increased. Specifically, 9 (with spacer of C₁₀H₂₀) demonstrated the towering antibacterial capability, superior to 5~6 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.