侧链衍生季铵盐型氯胺的合成及抗菌应用  

Synthesis of Side Chain Derived Quaternary Ammonium N-Chloramines for Antibacterial Applications

作　　者：李令东[1,2] 张颂伟 张维伦 刘鹏飞[2] 于江际鸣 周豪[2] LI Ling-Dong;ZHANG Song-Wei;ZHANG Wei-Lun;LIU Peng-Fei;YU Jiang-Jiming;ZHOU Hao(State Key Laboratory of Fine Chemicals,Dalian University of Technology,Panjin 124221,China;School of Chemical Engineering,Life and Ocean Science,Dalian University of Technology,Panjin 124221,China)

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

出　　处：《应用化学》2024年第7期966-975,共10页Chinese Journal of Applied Chemistry

基　　金：国家自然科学基金(No.41977197)资助。

摘　　要：以5,5-二甲基海因(DMH)为原料,设计合成了一系列侧链衍生的季铵盐型氯胺抗菌剂(10-14),表征了前体和氯胺结构。以大肠杆菌(E.coli)和金黄葡萄球菌(S.aureus)为模式菌株,以三甲基季铵盐氯胺1为对照,初步测试了氯胺10-14的抗菌活性。结果表明,氯胺10-13抗菌能力随侧链变长先增强后减弱,其中三丁基季铵盐氯胺12对S.aureus和E.coli的杀灭对数(KL)值分别为1.07±0.09和6.49,表现出这一系列中相对更优的抗菌活性,这可能是12达到了分子触杀所需的最佳亲疏水平衡状态,与菌体细胞膜作用更强所致。此外,携羟乙基侧链氯胺14实现了对S.aureus和E.coli全杀,展现了10-14中最出色的抗菌性能,这可能和氯胺分子更易穿透菌体细胞膜有关。本工作制备的一系列高活性季铵盐氯胺抗菌剂,为更高效离子型氯胺抗菌剂的设计研发提供了参考借鉴。A series of side-chain derived quaternary ammonium(QA)N-chloramines(10-14)were designed and synthesized using commercial 5,5-dimethylhydantoin(DMH)as raw matesial,and the structures of precursors and corresponding N-chloramines were characterized.The antibacterial activity of chloramines 10-14 was preliminarily tested using Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)as model strains,and N-chloramine 1 as control.The results showed that antibacterial ability of 10-13 increased and then declined with the length of side chain increased.Namely,tributyl QA N-chloramine 12 with KL of 1.07±0.09 and 6.49 against S.aureus and E.coli,exhibited relatively higher antibacterial efficacy,possibly due to the preferable hydrophilic-lipophilic characteristic required for efficient contact killing.Furthermore,hydroxyethyl counterpart 14 achieved total killing of S.aureus and E.coli,demonstrating the towering antibacterial capability among N-chloramines 10-14,which may be attributed to its facile transportation across bacterial cell membrane.The series of efficacious N-chloramine disinfectants prepared in this work provide reference for the development of more efficient ionic N-chloramine antibacterial agents.

关 键 词：季铵盐型氯胺 多步合成 抗菌活性 亲疏水平衡 侧链衍生物 

分 类 号：O626.2[理学—有机化学]