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
李令东 1张维伦 2刘鹏飞 2周子杰 2周豪 2杜中田1
作者信息
- 1. 大连理工大学精细化工国家重点实验室 辽宁盘锦 124221;大连理工大学化工海洋与生命学院 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
- 折叠
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.
Abstract
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-l-yl)propyl)-N,N,N,N-tetramethyldecane-l,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 tow-ering 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 bio-cidal and hydrophilic-lipophilic characteristic greatly contributes efficient contact killing.This study provides a series of effi-cacious 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Key words
Gemini-QA N-chloramine/ploy-step chemical synthesis/antibacterial activity/hydrophilic-lipophilic balance/biocidal team effort引用本文复制引用
基金项目
国家自然科学基金(41977197)
国家自然科学基金(22172010)
出版年
2024
NETL
NSTL
万方数据