Synthesis And Antimicrobial Application Of Betaine N-Chloramines

Communicable diseases caused by pathogenic infections have seriously threatened people's health and consequently resulted in huge economic loss.There is an urgent need to develop highly effective antimicrobial agents and antimicrobial materials to inhibit or kill pathogenic microorganisms.Over past decades,N-chloramines have been widely favored because of high-efficiency and broad-spectrum antimicrobial activity.However,the relative ly poor hydrophilicity limits their practicality greatly.To this end,our group developed quaternary ammonium?QA?N-chloramines,pyridinium salt N-chloramines and quaternary phosphonium N-chloramines recently.The introduced onium salt unit resulted in greatly enhanced aqueous solubility as well as increased the antibacterial activity.It has been well documented that betaine compounds usual y possess excel ent water solubility,biocompatibilit y,biodegradability,bactericidal and antifouling properties.Given this consideration,a series of betaine N-chloramines,which covalently linked an N-chloramine moiety and a zwitterio nic moiety,were designed and chemically synthesized.Escherichia coli?ATCC 25922?and Staphylococcus aureus?ATCC 25923?were used as modal strains to test its antibacteria l activity.The main contents are as follows:Two novel betaine N-chloramines,sulfobetaine N-chloramine and carboxybetaine N-chloramine,were chemical synthesized using 5,5-dimethyhydatoin,1,3-dibromopropane,1,3-propane sultone and sodium chloroacetate as raw materials.The structures of these two N-chloramines and all intermediates were characterized by NMR and HRMS analysis.A series of sulfobetaine N-chloramines,which contains varied linker length between the two opposite charged groups,were chemical synthesized by quaternization,sulfonation and chlorina t io n using DMH,1,n-dibromoalkane and sodium sulfite as raw materials.All prepared sulfobeta ine N-chloramines and intermediates were characterized by NMR and HRMS analysis.The previously reported QA N-chloramine was used as control for our antibacterial tests.Antimicrobial tests showed the bactericidal activity of sulfobetaine N-chloramine was slight ly inferior to that of QA N-chloramine,while the carboxybetaine N-chloramine was superior to QA N-chloramine.The result may be attributed to their hydrophilicity,charge density of betaine headgroup and the distribution density of biocides on the cell surface.In addition,antimicrobial tests also showed that with the linker length between the charged groups increased from the-?CH₂?₂-to-?CH₂?₈-,antimicrobial activity declined in turn,except the sulfobetaine N-chloramine with the linker of-?CH₂?₆-which displayed exceptiona l antimicrobial activity probably owing to the existence of noticeable ring strain.Meanwhile,sulfobetaine N-chloramine with the linker of-?CH₂?₁₀-exhibited the highest the bactericida l activity among all the synthetic N-chloramines,probably due to its neutral structure nature in aqueous conditions.