双子季铵盐氯胺的合成及抗菌应用  

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

作　　者：李令东[1,2] 张维伦 刘鹏飞[2] 周子杰 周豪[2] 杜中田[1,2] Lingdong Li;Weilun Zhang;Pengfei Liu;Zijie Zhou;Hao Zhou;Zhongtian Du(State Key Laboratory of Fine Chemicals,Dalian University of Technology,Panjin,Liaoning 124221;School of Chemical Engineering and Life&Ocean Science,Dalian University of Technology,Panjin,Liaoning 124221)

机构地区：[1]大连理工大学精细化工国家重点实验室,辽宁盘锦124221 [2]大连理工大学化工海洋与生命学院,辽宁盘锦124221

出　　处：《有机化学》2024年第6期2041-2048,共8页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.41977197,22172010)资助项目。

摘　　要：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.

关 键 词：双子季铵盐氯胺 化学多步合成 抗菌活性 亲疏水平衡 “团队”抗菌效应 

分 类 号：O626[理学—有机化学]