Synthesis And In Vitro Anticancer Activity Of Complexes Of Iridium And Ruthenium With Imine Nitrogen Heterocyclic Carbene Metal

Cancer is one of the greatest challenges facing humanity in today's world.Platinum chemotherapeutic drugs represented by cisplatin are widely used in clinical treatment of different cancers,but serious side effects and gradually acquired drug resistance limit their further development.As a result,more and more researchers are working to develop different metal anticancer drugs to overcome the limitations of platinum-based chemotherapy drugs.In recent years,the transition metal iridium???and ruthenium???complexes bearing some advantages,such as,the structural variability,the tendency to undergo ligand exchange reaction and the anti-tumor mechanism different from cisplatin et al,which has attracted extensive attention from the metal organic chemistry community.Based on the structural variability and modification of the iridium???and ruthenium???complexes,a series of iridium???and ruthenium???complexes with different substituents were synthesized by reasonable structural design.Moreover,their chemical properties,reaction with biomolecules,anticancer structure-activity relationship,and anticancer activity mechanisms also been exploited.The following is a brief introduction to the research content:The first part reports the synthesis of the imine-N-heterocyclic carbene ligands and the synthesis,characterization,anticancer and antibacterial activity of 12 new half-sandwich iridium???complexes[??⁵-Cp^x?Ir?C^N?Cl]PF₆[Cp^x=pentamethylcyclopentadienyl?Cp*?;tetramethyl?biphenyl?-cyclopentadienyl(Cp^xbiph);C^N=imine-N-heterocyclic carbene ligands with different substituents].The structure of these complexes was confirmed by ¹H NMR,X-ray single crystal diffraction,mass spectrometry and elemental analysis.Moreover,the structural-activity relationship of these complexes against A549 cells was established,and the antitumor activity mechanism was tested by flow cytometry and confocal microscopy imaging.In the second part,ten kinds of novel imine-N-heterocyclic carbene half-sandwich ruthenium???complexes were designed and synthesized,and their structural formula is[??⁶-p-cymene?Ru?C^N?Cl]PF₆.In the ligand framework of this complex,the influence of the substituent effect of the three tunable domains on the antitumor activity and the catalytic ability in converting coenzyme NADH to NAD⁺was discussed.Despite the structural similarities of these complexes,such complexes exhibited significantly different anticancer activity against A549 cancer cells.In the third part,five cyclometalated iridium???complexes[Ir?ppy?₂?C^N?]PF₆ containing imine-N-heterocyclic carbene were synthesized and fully characterized.All complexes Ir1–Ir5showed high cytotoxicity against A549 cells with IC₅₀ values ranging from 1.78 to 4.95?M.Ir5was particularly potent towards A549 cancer cells(IC₅₀=1.78?M)and had ca.12-fold higher cytotoxicity than cisplatin.In addition,the absorption and emission spectra of such complexes are systematically investigated.Complexes Ir2 and Ir5 show moderate binding affinity to BSA and the fluorescence quenching of BSA by the iridium???complexes is due to the static quenching.