Synthesis, Properties And Anticancer Activity Of Ionic Metal Iridium And Ruthenium Complexes

The successful research and development of the anticancer drug cisplatin has made medical inorganic chemistry an independent subject.However,with many problems in the clinical application of cisplatin,scientists are focusing more on the development of anti-cancer drugs based on other metals(tin,palladium,silver,iridium,ruthenium,copper and titanium).These iridium and ruthenium metal-based anticancer drugs are mainly concentrated in the semi-sandwich iridium(?),ruthenium(?)complex and cycloiridium(?)complex,and most of them are neutral and cationic.In order to explore the effect of the charge and substitution pattern of the biodentate ligands on the biological activity of the complexes,the first system in this paper mainly studied the synthesis,characterization and biological activity of the zwitterionic half-sandwich iridium(?)and ruthenium(?)complexes and the zwitterionic cyclometalated iridium(?)complexes.In the other system,a solvent was involved in the rearrangement reaction,resulting in the accidental synthesis of a five-coordination half-sandwich ruthenium(?)complex.The reaction mechanism and biological properties of the complexes were evaluated.The anticancer complexes of the two systems can improve the understanding of the structure-activity relationship of the novel anticancer complex of transition metal.1.Previous studies on neutral and cationic half-sandwich iridium(?)and ruthenium(?)complexes have shown that the bidentate ligands have significant effects on their bioactivity due to their charge and substitution modes as well as the properties of counterbalance ions.However,few studies have been done on zwitterionic and cationic iridium(?)and ruthenium(?)complexes containing sulfonated groups.A series of zwitterionic and cationic iridium(?)and ruthenium(?)complexes have been prepared and characterized.The position of counterbalance ions in these two complexes has a great influence on the killing activity of cancer cells.Various possible mechanisms of action were examined by flow cytometry.This study is the first to reveal the difference in bioactivity between zwitterionic and cationic half-sandwich metal complexes.2.In the previous section,we reported a series of zwitterionic and cationic half-sandwiched iridium(?)and ruthenium(?)complexes,and compared the differences in the anticancer mechanisms between the two types of complexes.Among them,the cationic complexes showed good anticancer activity.Unfortunately,the antitumor activity of zwitterionic complexes is low.The two different biological behaviors may be caused by the difference in hydrophobicity between the zwitterionic and cationic complexes.This conjecture allows us to further modify the zwitterionic ion type complex,so that the complex has better anticancer activity.Studies have shown that fluorine substitution strategy is widely used in the design of organic small molecule drugs.The introduction of fluorine atoms or fluorine-containing groups into organic small molecules can effectively increase the lipophilicity of the drugs.Thus,a series of zwitterionic half-sandwich iridium(?)complexes containing different fluorine substituents in the ?5-CpR ring are reported in this section.The effect of substituents on the ?5-CpR ring of zwitterionic complexes on their anticancer activity was systematically studied.Happily,the presence of fluorine substituents significantly increased the anticancer activity.Lipophilicity and cellular uptake levels of these complexes may be the main factors influencing cytotoxicity in this system.Micromechanism studies showed that complex Ir10 entered A549 cancer cells through an energy-dependent pathway,mainly located in lysosomes.In addition,increased ROS levels,induction of cell apoptosis and disturbance of cell cycle jointly promote the anticancer ability of these zwitterionic complexes.3.Metallic anticancer drug development is mainly focused on half-sandwich iridium(?),ruthenium(?)complexes and cyclometalated iridium(?)complexes.The first two sections were mainly composed of zwitterionic half-sandwiched iridium(?)complexes,followed by four fluorescent zwitterionic cyclometalated iridium(?)complexes(Ir14-Ir17)containing different sulfonated imidopyridine ligands.The solid molecular structure of Ir14 was determined by X-ray crystal diffraction.These fluorescent zwitterionic complexes are very stable in aqueous solution and have detectable fluorescence.The fluorescence properties of the complexes make it possible to determine their microscopic mechanisms by cell imaging and to study the manner of cell death by flow cytometry.4.A series of unsaturated half-sandwich ruthenium(?)complexes were accidentally synthesized and characterized by solvent rearrangement reaction.The electrochemical behavior and luminescent properties of the complexes were also studied.Compared with cisplatin,this complexes is stable enough to have higher anticancer activity against A549(human lung cancer cells),He La(human cervical cancer cells)and Hep G2(liver cancer cells).By studying the structure-activity relationship of the complexes,it was found that Ru5 with hydrophobic groups had stronger anticancer activity compared with Ru5 and Ru7 containing hydroxyl groups.The complex Ru5 entered A549 cells through a non-energy dependent pathway and was mainly accumulated in lysosomes.