Construction Of Phosphorus Photocyclic Metal Iridium(Ⅲ) And Platinum(Ⅱ)complexes With Intracellular And Extracellular Stimulation Responses And Their Application As Antitumor Diagnostic And Therapeutic Reagents

Cancer has become one of the main causes of human death.Scientists have developed platinum complexes such as cisplatin and carboplatin as anticancer drugs,but their side effects are serious,and the most important thing is acquired drug resistance.In order to overcome these limitations,an effective strategy is to change the metal core of the complex and introduce different coordination modes of the metal core,thus the cyclometalated complex comes into being.In recent years,materials with optical properties that can change under different external stimuli have great application potential in various biomedical fields.In addition to traditional organic small molecules,cyclic metal complexes have attracted much attention due to their abundant excited states,high sensitivity to small changes in the surrounding environment,adjustable ligand and metal centers,and long luminous life.Based on the above background,the research content of this paper is as follows:1.Phosphorescent complexes with the structure of Ir(Ⅲ)with single,double and tetrad nucleated rings were synthesized using bpy as a mononucleate ligand.It was found that the dissociation rate of mononucleate ligand was mononucleate>binucleate>tetrad under external stimuli such as light and GSH.At the same time,the free metal center will bind to the histidine or the protein containing histidine group in the cell,and the orange phosphorescence of the complex at 625±20 nm and the green phosphorescence at 490±20 nm in the solution will be reduced.The changes in fluorescence intensity of the two channels observed by flow cytometry and laser confocal can be used for real-time monitoring of dual-channel imaging of living cells.Further studies showed that with the extension of incubation time of the complex to 4h,the orange and green luminescence of the complex could be transferred from the cytoplasm of living cells to the nucleus,at the same time,the active oxygen species of living cells could be increased,mitochondrial membrane potential could be depolarized,and the nucleus could be damaged and broken,effectively inducing programmed apoptosis of tumor cells.2.Three sets of cyclic metallized platinum(II)complexes were designed and synthesized as dynamic self-assembly mediated near-infrared(NIR)red phosphorescence opening probes for specific anions in aqueous solutions.As the number of aromatic rings in the NN bidentate ligand increases from 2 to 5,the Pt-Pt interaction between the molecules weakens,showing a decrease in the intensity of near-infrared switching phosphorescence emission.The increase in ligand hindrance is 138.32 folds when the ligand hindrance is small,and 6.64 folds when the hindrance is large.In addition,we studied for the first time the effect of different substituents in CN ligands on the specific recognition of multiple anions.Compared with complexes with electron donor groups containing S atoms or similar structures without any substituents,Pt complexes with electron withdrawing groups substituted by F atoms showed the best specific sexual selection for Br~-.More interestingly,the bright green emission caused by the interaction between cellular biomolecules and Pt(II)complexes facilitates real-time monitoring of the subcellular positions of Pt(II)complexes under different interactions.The changes in luminescence intensity of the two channels(red and green)recorded by flow cytometry can reflect the dynamic self-assembly processes of the complexes in living cells,further indicating the changes of platinum complexes in their interactions with different molecules.In addition,it was found for the first time that these complexes can activate a relatively unusual mode of death in cancer cells-cell oncosis.Further suggesting that our work may provide a promising strategy for developing a new type of drug to treat cancer.