Study On The Targeting And Anticancer Mechanism Of Organotin (IV) And Iridium (III) Compounds With AIE Effec

In the process of drug development,it is indispensable to study its targeting and metabolic cycle.The common research idea is to endow drugs with fluorescence characteristics,and using fluorescence to track and monitor drugs in cells real-time.However,aggregation-caused quenching(ACQ)causes the fluorescence quenching of most fluorescent materials at a certain concentration,which is difficult to trace.Since the 21 st century,a large number of compounds with aggregation-induced emission(AIE)characteristics have been designed and synthesized,showing the opposite characteristics of ACQ effect.That is,the luminescence in solution is weak,but improved in solid state,which providing a new idea for the design of fluorescent probes and fluorescent drugs.In view of the potential application value of organotin(Ⅳ)compounds and cycloiridium(Ⅲ)complexes in the anticancer field,and the anticancer mechanism is not clear up to now,a series of organotin(Ⅳ)acylhydrazone compounds and cycloiridium(Ⅲ)bipyridine complexes with AIE properties were designed and developed in this paper,and their AIE luminescence mechanism was also studied.The targeting,anticancer mechanism,absorption mechanism and anticancer channel of these compounds were studied by using their good fluorescence characteristics.The details are as follows:1.A triphenyltin(Ⅳ)-triphenylamine acylhydrazone compound(Sn TPA)with AIE properties was designed and developed.The introduction of acylhydrazone groups and triphenylamine molecules with large steric hindrance inhibited π-π stacking between adjacent molecules,resulting in obvious fluorescence improvement in the aggregated state.The absolute fluorescence quantum yield of Sn TPA in solid state is 12.6%,showing a blue-green fluorescence emission.The change of luminescence intensity of Sn TPA was studied by regulating the viscosity of solution.The accumulation of molecules in the aggregation state was also studied.The restriction of intramolecular rotation(RIR)was the main mechanism of AIE properties of Sn TPA.Using the excellent luminescence,confocal test confirmed that Sn TPA could target lysosomes of A549 cells,induce lysosome damage,and show anticancer activity.Flow cytometry further confirmed that Sn TPA could block the cell growth cycle(S phase),induce the accumulation of intracellular reactive oxygen species(ROS),and eventually lead to cell apoptosis.In addition,Sn TPA not only showed good inhibitory activity on the proliferation of A549 lung cancer cells,but also could inhibit the migration of A549 cells,showing obvious bi-functional characteristics.2.A series of triphenyl/diphenyltin(Ⅳ)-tetraphenylethylene(TPE)acylhydrazone compounds with AIE properties were designed and developed,the diphenyltin(Ⅳ)chloride(Cl Sn TPE)had the highest absolute fluorescence quantum yield(25.2%),showing a blue-green emission and AIE property with a mechanism of limited intramolecular rotation.Laser confocal detection showed that Cl Sn TPE could accumulate in the mitochondria of A549 cells,reduce the mitochondrial membrane potential,increase the intracellular ROS,block cell growth cycle(G1 phase),and ultimately induce apoptosis.In terms of structure-activity relationship,the diphenyltin(Ⅳ)compounds showed better antiproliferative activity than the triphenyltin(Ⅳ)compound,and could effectively inhibit the migration of A549 cells.3.Two triphenylamine/phenylcarbazole-modified cycloiridium(Ⅲ)bipyridine complexes with AIE properties were designed and developed.The introduction of triphenylamine and phenylcarbazole gives these complexes excellent AIE properties.The absolute fluorescence quantum yield in the aggregated state is 10.6%(Ir-CA).The luminescence mechanism is limited intramolecular rotation.Targeted studies have confirmed that Ir-CA can accumulate in the lysosomes of A549 cells,induce lysosome damage,lead to the changes of nuclear morphology,decrease mitochondrial membrane potential,and ultimately induce apoptosis.Western blotting also confirmed the existence of lysosome-mitochondria anticancer pathway.In addition,Ir-CA could inhibit the migration of A549 cells,disrupt the cell growth cycle(G1 phase),lead to the accumulation of intracellular ROS,then exhibit anticancer activity.