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

doi:10.6023/cjoc202312028

Chinese Journal of Organic Chemistry ›› 2024, Vol. 44 ›› Issue (6): 2041-2048.DOI: 10.6023/cjoc202312028 Previous Articles Next Articles

双子季铵盐氯胺的合成及抗菌应用

李令东^a^,^b^,^*(), 张维伦^b, 刘鹏飞^b, 周子杰^b, 周豪^b, 杜中田^a^,^b

a 大连理工大学精细化工国家重点实验室辽宁盘锦 124221
b 大连理工大学化工海洋与生命学院辽宁盘锦 124221

收稿日期:2023-12-29 修回日期:2024-02-08 发布日期:2024-03-12
基金资助:
国家自然科学基金(41977197); 国家自然科学基金(22172010)

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

Lingdong Li^a^,^b,*(), Weilun Zhang^b, Pengfei Liu^b, Zijie Zhou^b, Hao Zhou^b, Zhongtian Du^a^,^b

a State Key Laboratory of Fine Chemicals, Dalian University of Technology, Panjin, Liaoning 124221
b School of Chemical Engineering and Life & Ocean Science, Dalian University of Technology, Panjin, Liaoning 124221

Received:2023-12-29 Revised:2024-02-08 Published:2024-03-12
Contact: * E-mail: lild@dlut.edu.cn
Supported by:
National Natural Science Foundation of China(41977197); National Natural Science Foundation of China(22172010)

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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-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.

Key words: Gemini-QA N-chloramine, ploy-step chemical synthesis, antibacterial activity, hydrophilic-lipophilic balance, biocidal team effort

Cite this article

Lingdong Li, Weilun Zhang, Pengfei Liu, Zijie Zhou, Hao Zhou, Zhongtian Du. Synthesis of Gemini-Quaternary Ammonium N-Chloramine Biocides for Antibacterial Applications[J]. Chinese Journal of Organic Chemistry, 2024, 44(6): 2041-2048.

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细菌	化合物	活性氯/(mmol•L^–1)	接触5 min		接触10 min
细菌	化合物	活性氯/(mmol•L^–1)	减少量/%	log减少值	减少量/%	log减少值
S. aureus^a	5a	0	0	0	0	0
	5	0.56	83.99±2.94	0.80±0.07	100	6.79
	6a	0	0	0	0	0
	6	0.56	75.49±2.36	0.61±0.03	99.35±0.33	2.18±0.30
	7a	0	0	0	0	0
	7	0.56	41.18±1.96	0.23±0.02	98.37±0.33	1.79±0.08
	8a	0	0	0	0	0
	8 9a 9	0.56 0 0.56	52.61±0.65 0 99.35±0.33	0.32±0.01 0 2.18±0.30	100 0 100	6.79 0 6.79
E. coli^b	5a	0	0	0	0	0
	5	0.56	88.07±3.67	0.92±0.12	100	6.34
	6a	0	0	0	0	0
	6	0.56	87.16±1.83	0.89±0.06	100	6.34
	7a	0	0	0	0	0
	7	0.56	62.39±1.83	0.42±0.09	100	6.34
	8a	0	0	0	0	0
	8	0.56	86.14±3.67	0.86±0.10	100	6.34
	9a	0	0	0	0	0
	9	0.56	100	6.34	100	6.34

细菌	化合物	活性氯/(mmol•L^–1)	接触5 min		接触10 min
细菌	化合物	活性氯/(mmol•L^–1)	减少量/%	log减少值	减少量/%	log减少值
S. aureus^a	5a	0	0	0	0	0
	5	0.56	83.99±2.94	0.80±0.07	100	6.79
	6a	0	0	0	0	0
	6	0.56	75.49±2.36	0.61±0.03	99.35±0.33	2.18±0.30
	7a	0	0	0	0	0
	7	0.56	41.18±1.96	0.23±0.02	98.37±0.33	1.79±0.08
	8a	0	0	0	0	0
	8 9a 9	0.56 0 0.56	52.61±0.65 0 99.35±0.33	0.32±0.01 0 2.18±0.30	100 0 100	6.79 0 6.79
E. coli^b	5a	0	0	0	0	0
	5	0.56	88.07±3.67	0.92±0.12	100	6.34
	6a	0	0	0	0	0
	6	0.56	87.16±1.83	0.89±0.06	100	6.34
	7a	0	0	0	0	0
	7	0.56	62.39±1.83	0.42±0.09	100	6.34
	8a	0	0	0	0	0
	8	0.56	86.14±3.67	0.86±0.10	100	6.34
	9a	0	0	0	0	0
	9	0.56	100	6.34	100	6.34

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

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