Study On The Antibacterial Activity Of Iridium(?) Or Ruthenium(?) Complexes

Nowadays,the bacterial infectious diseases are one of the major challenges facing the global public health community.Bacterial infection causes more and more diseases,causing concern from all walks of life.However,the problem of bacterial resistance has become increasingly serious.What's more,drug-resistant bacteria have brought many difficulties to clinical treatment.Therefore,the study of new antimicrobial agents is particularly important for humans.The researchers mainly aimed at modifying the structure of existing existiing synthetic antimicrobial agents,drug resistance mechanism and structure-activity relationship.Although the early metal antibacterial drug Safanfusan and the early anticancer drug cisplatin have achieved great successes in antibacterial and antitumor.They have large toxic and side effects,which have caused widespread concern.Compared with cisplatin,ruthenium???complexes have the advantages of small toxic and side effects,good antibacterial and anticancer effects,which made it popular to researchers.In addition,iridium???complexes also have good anticancer and antibacterial activities.Finding new antibacterial agents and studying on their antibacterial mechanisms can improve drug resistance to pathogenic bacteria.Therefore,this paper mainly studies the synthesis and antibacterial activity of iridium???and ruthenium???metal complexes.The first chapter mainly introduces the research of bacteria,organic antibacterial agents,and metal complex antibacterial agents.The Chapter 2,we synthesize four Iridium???complexes,inclouding[FIr?dfppy?₂]Cl?Ir-1??[FIr?bzq?₂]Cl?Ir-2??[FIr?thpy?₂]Cl?Ir-3?and[FIr?ppy?₂]Cl?Ir-4?.These complexes were characterized by elemental analysis,mass spectrometry,and nuclear magnetic resonance proton spectroscopy.The antimicrobical activity of Ir???complexes were tested in vitro against S.aureus?ATCC 25923?,E.coli?ATCC 25922?and A.fumigatus?ATCC 1022?bacteria.As for the preliminary screen,the complex Ir-3 exhibited the best antibacterial effect.The results of bacterial colocalization showed that Ir-3 complexes selectively target RNA over DNA in vitro.The changes in morphology and membrance integrity of S.aureus?E.coli and A.fumigatus treated with complex Ir-3were evaluated by SEM images.Ir-3 complex caused the bacterical death through cell membrane disruption.Furthermore,the MIC of complex Ir-3toward S.aureus did not change even after 24 passages,whereas the MIC of streptomycin increased by 256-fold.Thus,bacteria are less likely to acquire resistance complex Ir-3 compared to clinically used untibitotics such as streptomycin.In addition,the accumulation of Ir-3 complex in the three bacterial strains was shown to increase with increasing incubation temperature.Whereas,the relative increase in accumulation greater with E.coli and A.fumigatus was observed.No decrease in accumulation was observed for Ir-3 complex in ATP-inhibited cells.Carbonyl cyanide m-chlorophenyl hydrazone?CCCP?did depolarize the cell membrane,and no reduction in the accumulation of Ir-3 complex was observed.In addition,Ir-3 complex was allowed a greater quantity of the membrane-impermeable dye TO-PRO-3 taken up by S.aureus?E.coli and A.fumigatus.The chapter 3,we synthesize three mononuclear metal ruthenium???complexes,including[CMRu?dmb?₂]Cl₂?Ru-1??[CMRu?dip?₂]Cl₂?Ru-2??[CMRu?phen?₂]Cl₂?Ru-3?.These complexes were characterized by elemental analysis,mass spectrometry,and ¹H NMR.For a preliminary antibacterial activity study,the antibacterial activity was evaluated by the minimal inhibitory concentration?MIC?and minimum bactericidal concentration?MBC?.As for the preliminary screen,Ru-1complex had the best antibacterial effect.The changes in morphology and membrance integrity of S.aureus?E.coli and A.fumigatus treated with complex Ru-1 were evaluated by SEM images.Ru-1 complex caused the bacterical death through cell membrane disruption.The results of bacterial colocalization showed that the Ru-1 complex selectively target RNA over DNA in vitro.Furthermore,the MIC of complex Ru-1 toward S.aureus did not change even after 24 passages,whereas the MIC of streptomycin increased by 256-fold.Thus,bacteria are less likely to acquire resistance complex Ru-1 compared to clinically used untibitotics such as streptomycin.In addition,the accumulation of Ru-1 complex in the three bacterial strains was shown to increase with increasing incubation temperature.whereas,the relative increase in accumulation greater with E.coli and A.fumigatus was observed.No decrease in accumulation was observed for Ru-1 complex in ATP-inhibited cells.Carbonyl cyanide m-chlorophenyl hydrazone?CCCP?did depolarize the cell membrane,and no reduction in the accumulation of Ru-1 complex was observed.In addition,Ru-1 complex was allowed a greater quantity of the membrane-impermeable dye TO-PRO-3 taken up by S.aureus?E.coli and A.fumigatus.The chapter 4,Synthesis of three iridium???complexes by changing the dimeric bridge structure of the ligand and the ring metal iridium???,including[CMIr?ppy?₂]Cl?Ir-5?,[[CMIr?thpy?₂]Cl?Ir-6?,CMIr?bzq?₂]Cl?Ir-7?.These complexes were characterized by elemental analysis,mass spectrometry,and ¹H NMR.As for the preliminary screen,iridium???complexes had shown appreciable antibacterial activity against Staphulococcus aureus and methicillin-resistant?MRSA?.The changes in morphology and membrance integrity of S.aureus and MRSA treated with complex Ir-5were evaluated by SEM images.Ir-5 complex caused the bacterical death through cell membrane disruption.The results of bacterial colocalization showed that the Ir-5 complex selectively target RNA over DNA in vitro.Furthermore,the MIC of complex Ir-5 toward S.aureus did not change even after 24 passages,whereas the MIC of streptomycin increased by256-fold.Thus,bacteria are less likely to acquire resistance complex Ir-5compared to clinically used untibitotics such as streptomycin.