Electronic Effects And Counter Ion Effects In Metal Iridium Anticancer Complexes

Cancer has become a disease that seriously affects human health,Platinum（II）metal antitumor drugs represented by cisplatin have been successfully used in clinical chemotherapy for cancer treatment,but Platinum（II）drugs have the disadvantages of large side effects and easy to produce drug resistance.Therefore,it was necessary to find alternatives to cisplatin anti-tumor drugs.The organometallic iridium（III）complexes were structurally multifunctional,potential redox properties and the wide range of ligand modifiability have attracted the interest of researchers.The paper discusses the following two parts:1)The effect of electronic effects on the reactivity and anticancer activity of half-sandwich iridium（III）complexes;2)The effect of different counterions on the anticancer activity of complex salts of iridium（III）complexes:Twelve iridium（III）complexes of two systems were synthesized,the complex 4was reported previously.The first part was the introduction of electron-donating groups（-NH₂,-OH,-OCH₃）and electron-withdrawing groups（-Cl,-NO₂）on N,N-bipyridyl chelate ligands of half-sandwich iridium（III）complexes.To study the effect of electronic effects on the reactivity and anticancer activity of complexes.The crystal structures of complexes 1,3,5 and 6 were obtained.The structures were characterized by means of nuclear magnetic resonance（NMR）and elemental analysis.The chemical and catalytic activities were tested.It has been found that different electron groups have a certain influence on the hydrolyzability and catalytic activity of compounds.The electron-donating groups cause the reduction of the anti-cancer activityoutsidethecomplex,whilethe complexescontainingthe electron-withdrawing groups have enhanced anti-cancer activity.Complex 1 and 6showed a certain selectivity for A549 human lung cancer cells and human bronchial epithelial normal cells BEAS-2B and 16HBE.The surface electrostatic potential of the complex was calculated using density functional theory（DFT）.Flow cytometry instrument to detect the cancer cells in vitro,cell cycle and cell apoptosis in the study of reactive oxygen species,found that complex 6 containing the strongest electron-withdrawing groups NO₂ have better bioactivity than others,demonstrated the influence of electronic effect on complexes antitumor activity.The second part was the study of the effect of counteranion size and coordination ability on the anticancer activity of N,N-dipyridyl chelated iridium（III）complexes.Synthesize the iridium complexes with Cl^-,BF₄^-,SbF₆^-,CF₃SO₃^-,BPh₄^-,and BArF^-（[3,5-（CF₃）₂Ph]₄B^-）to obtain the crystal structure of complex 11.Studies have shown that there were weakπ-πinteractions in the complexes of large and weakly coordinated counter anions BPh₄^-.Complexes 7-10 containing small volume counter-ions exhibited good in vitro anti-cancer activity against A549 human lung cancer cells,whereas complexes 11,12 containing large volume counter anions did not exhibit cellular activity.Changes in counterions can affect the chemical and catalytic activity of complexes and have an effect on cell cycle,apoptosis,intracellular reactive oxygen species levels and mitochondrial membrane potential.The complex 10 with anticancer activity blocked the cell cycle,induced apoptosis and significantly changed the level of reactive oxygen species and mitochondrial membrane potential in cancer cells;However,complex 11 without anticancer activity had almost no apparent effect when tested under the same conditions.The specific mechanism of action on apoptosis and cycle needs further studied.In this paper,the influence of electron effect and counter ion on the chemical and anti-cancer activity of metal iridium complex was studied.The new strategy was provided for the design of anticancer drug for metal complex.