Synthesis, Characterization And Anti-tumor Application Of Triphenylamine-modified Metal Iridium(?)N^N And C^N Complexes

At present,due to the genetic and environmental carcinogenic factors,human beings worldwide are suffering a fatal blow to cancer.Therefore,it is urgent to develop anticancer drugs.Among which metal anticancer drugs have attracted more and more attention.Cisplatin has been used clinically as a representative of metal anticancer drugs and has shown good therapeutic effects.However,serious toxic side effects and drug resistance cannot be ignored.Therefore,the development of new metal anticancer drugs is urgently needed.Among them,although iridium itself has the characteristics of inertia,compared with the clinically used anticancer complexes cisplatin,the metal iridium?III?complexes often show an octahedral structure,which makes the structure of the metal iridium complex variable and provides a broader space for its structure modification.In addition,iridium anticancer complexes have good anticancer ability,high stability,extensive biological applications and anticancer mechanisms different from platinum anticancer complexes.This article mainly designs and synthesizes two types of triphenylamine modified half-sandwiched structure metal iridium?III?anticancer complexes:?[??⁵-Cp^x?Ir?N^N?Cl]PF₆?and?[??⁵-Cp^x?Ir?C^N?Cl]?.The complexes were characterized by X-ray single crystal diffraction,nuclear magnetic hydrogen spectrum?¹H NMR?,nuclear magnetic carbon spectrum(¹³C NMR),mass spectrometry?ESI-MS?,fluorescence spectrum,and ultraviolet spectrum.In addation,the MTT method was used to test the anti-cancer ability of these complexes against different cancer cells and to screen representative complexes for the study of anti-cancer mechanisms.Finally,the localization of typical complexes in A549 cancer cells was tracked by laser confocal microscopy.The details are as follows:1.In this study,six triphenylamine modified half-sandwiched structure metal iridium?III?Schiff base?N^N?anticancer complexes?[??⁵-Cp^x?Ir?N^N?Cl]PF₆?were designed and characterized.First,the cytotoxicity of this series of complexes on cancer cells was obtained?MTT method?,which showed that the anti-cancer activity of these complexes(IC₅₀:1.4±0.1?M?11.5±0.5?M)were significantly improved.The introduction of coordination group of triphenylamine Schiff base was found to be an important reason.It is worth noting that this series of complexes have the ability to inhibit cell migration while exhibiting antitumor activity,which lays the foundation for its anticancer application.In addation,the catalytic oxidation of the coenzyme nicotinamine-adenine dinucleoside?NADH?experiments and flow cytometry confirmed that such complexes can promote the production of reactive oxygen species?ROS?in A549 cells,which leading to tumor cell death,confirming its oxidation anti-cancer mechanism.At the same time,the laser confocal test confirmed that these complexes can enter tumor cells through an energy-dependent uptake mechanisms and targeted lysosomes tissue of A549 cells?confocal coefficient Pearson:?0.75?,and resulting in lysosomal damage,disrupting the cell growth cycle,the mitochondrial membrane potential is induced to decline,and eventually leading to apoptosis.2.In this study,ten triphenylamine modified half-sandwiched structure metal iridium?III?Phenylpyridine?C^N?anticancer complexes?[??⁵-Cp^x?Ir?C^N?Cl]?were designed and characterized.The anticancer activity of complexes 1-10 on A549?human lung cancer cells?and HeLa?human cervical cancer cells?were measured by MTT method.These complexes all showed good anticancer effects and inhibited migration ability.Among them,complex 5 has the best activity,which is 8 times that of cisplatin.Laser confocal microscopy confirmed that these complexes entered cells in an energy-independent manner and were localized to lysosomes tissue in A549 tumor cells,and causing lysosomal damage.In addition,it was confirmed that these complexes may bind to proteins,through serum protein transport,catalyze the oxidation of NADH,and increase intracellular ROS levels by UV spectroscopy and flow cytometry,eventually leading to apoptosis.In general,triphenylamine modified half-sandwiched structure metal iridium?III?complexes exhibit dual antitumor functions that inhibit tumor cell migration and induce lysosomal damage,eventually leading to apoptosis,which provides a basic platform for the structural design of organometallic complexes.