Study On The Antibacterial Activity Of Metal Complexes Of Ruthenium And Iridium

Bacteria are single-celled prokaryotic microorganism.Bacterial infection can induce various diseases or even death.The research and development of antibacterial drugs have never been stopped since the invention of antibiotics.However,the antibiotics and other antibacterial drugs have such shortcomings as narrow antibacterial spectrum and high resistance.As study continues,it is found that transition metal complexes have a high antibacterial activity.Above all,the ruthenium（Ⅱ）and iridium（Ⅲ）complexes have attracted broad attention for their favorable photochemical and photophysical property,biocompatibility and antibacterial activity.This paper elaborates on our efforts in three parts.We study the antibacterial activity of the complex by changing the structure of the main ligand,and increasing the number of central metals in the complex and ancillary ligands of different structures.The first chapter is an introduction to the structure of bacteria,and histories of antibacterial drugs of organic compounds,rare earth metals and transition metals.The second chapter introduces the design and synthesis of four new iridium（Ⅲ）complexes,[Ir（ppy）₂（BHPYP）]Cl（Ir1）,[Ir（ppy）₂（HHPYP）]Cl（Ir2）,[Ir（ppy）₂（OHPYP）]Cl（Ir3）and[Ir（ppy）₂（DHPYP）]Cl（Ir4）,composed of main ligands with different carbon chain length by changing the main ligands.Ir1 with the shortest carbon chain was determined to present the best antibacterial activity via minimal inhibitory concentration（MIC）,minimal bactericidal concentration（MBC）,inhibition zone test,plate test,cold field scanning electron microscope and ICP-MS test.The values of MIC against Staphylococcus aureus,Escherichia coli and Aspergillus fumigatus were 2μg/mL、2μg/mL and 4μg/mL respectively.Such tests as bacterial co-localization test,DNA gel electrophoresis test,competition assay of complexes and ethidium bromide（EB）,and the test of the impact of complexes on the expression of DNA repair gene related to the replication of the Escherichia coli proved that Ir1 could damage the escherichia coli DNA and inhibit the DNA replication by combining with the Escherichia coli DNA via intercalation.The third chapter introduces the design and synthesis of two new heteronuclear complexes containing ruthenium（Ⅱ）and iridium（Ⅲ）,[Ru（bpy）₂Ir（dfppy）₂（PNPY）]Cl₃（Ru-Ir1）and[Ru（bpy）₂Ir（tpy）₂（PNPY）]Cl₃（Ru-Ir2）,with increased number of central metals in the complexes.Ru-Ir1 was determined to present the best antibacterial activity via minimal inhibitory concentration（MIC）,minimal bactericidal concentration（MBC）,inhibition zone test,plate test,cold field scanning electron microscope and ICP-MS test.The values of MIC against staphylococcus aureus,escherichia coli and aspergillus fumigatus were 4μg/mL、6μg/mL and 12μg/mL respectively.Such tests as bacterial co-localization test,DNA gel electrophoresis test,competition assay of complexes and ethidium bromide（EB）,and the test of the impact of complexes on the expression of DNA repair gene related to the replication of the escherichia coli proved that Ru-Ir1 could damage the DNA and inhibit the DNA replication by combining with the escherichia coli DNA via intercalation.The fourth chapter introduces the design and synthesis of four iridium（Ⅲ）complexes,[Ir（ppy）₂（BHPP）]Cl（Ir5）,[Ir（dfppy）₂（BHPP）]Cl（Ir6）,[Ir（benz）₂（BHPP）]Cl（Ir7）and[Ir（tpy）₂（BHPP）]Cl（Ir8）,by changing the structure of ancillary ligands.The in vitro antibacterial activity of Iridium（Ⅲ）complexes in this chapter against escherichia coli,staphylococcus aureus and aspergillus fumigatus were investigated via minimal inhibitory concentration（MIC）,minimal bactericidal concentration（MBC）,inhibition zone test,plate test,cold field scanning electron microscope,ICP-MS test,etc.The results demonstrated that Ir8 presented the best antibacterial activity,and the values of MIC against staphylococcus aureus,escherichia coli and aspergillus fumigatus were 1.58μg/mL、3.25μg/mL and 6.25μg/mL respectively.The bacterial co-localization test demonstrated that Ir8specifically accumulated in ribosome RNA of escherichia coli and aspergillus fumigatus.