Quaternary Ammonium(QA)N-chloramine Bactericidal Agents:Chemical Synthesis And Study On Structure-antibacterial Activity Relationship

Nowadays pathogen contaminations and cross infections represented by pathogenic microorganism,have been recognized as global prseeing public healthcare issues.Recently,the large-scale outbreak of 2019-n COV has haunted many countries.Therefore,it is of great significance to develop efficacious bactericidal agents to effectively control spread of pathogenic microorganisms.Due to the particular advantages of broad-spectrum,high efficacy and facile rechargeability,N-chloramine based antibacterial materials were successively developed.However,N-chloramines（N-Cl）usually bear reduced hydrophilicity,which greatly restricts contact killing efficacy and practical applications.As such,QA structure etc.were introduced into N-chloramine to obtain ionic N-chloramine antibacterial agents.The introduced cationic unit greatly improved aqueous solubility as well as significantly enhanced biocidal efficacy of N-Cl scaffold.In addition,further improved antibacterial efficacy was achieved if the structural methylene linker between DMH unit and cationic centre increases to-C₁₂H₂₅.This is due to the synergistic effect of long-chain alkyl onium salts and N-chloramines.At the same time,the Gemini-QA N-chloramine reported by this group recently exhibited significant team antibacterial effect.To further exploit structure-antibacterial activity relationship of cationic N-chloramines,this work intends to chemically synthesize a series of QA N-chloramines.The contents are as follows:A series of QA N-chloramine 14～20,21～26（Chapter two）,31～34（Chapter three）and35～38（Chapter four）starting from 5,5-dimethyl-hydantoin as row materials,were chemically synthesized with alkylation,quaternization and chlorination and characterized by NMR and HRMS analysis.Antibacterial activity of such newly synthetic N-chloramines was then investigated by challenging against E.coli（ATCC 25922）and S.aureus（ATCC 25923）.Antibacterial activity showed that the structural methylene linker between DMH unit and QA center was crucial for the overall antibacterial efficacy.Particularly,N-chloramine 14,with the simplest QA structure and if the charge-to-mass ratio is constant,21 with intact long alkyl chains can produce the superior antibacterial activity;as the linker between Gemini-QA and N-chloramine increases,the antibacterial activity first weakens and then increases,and the linker is the longest（34）among the antibacterial activity homologues,which is better than the reported Gemini-QA N-chloramine.It is speculated that the improvement of antibacterial activity is due to the change of the length of the alkyl chain between the QA unit and N-chloramine unit,as well as the special team antibacterial effect of Gemini structure;among trimethyl-derived QA N-chloramine,37 has the most outstanding antibacterial activity.It is speculated that the QA hydrophilic group at the end of 37 carries-C₄H₉ alkyl chains,which increases the hydrophobicity and has the QA hydrophilic head to achieve balance,which makes the N-chloramine easier to contact and sterilize.