Herein,we have designed,synthesized,and characterized two novel coumarin-6-based Ir(Ⅲ)photo-catalysts viz.[Ir(CO_(6))_(2)(dppz)]Cl(Ir1)and[Ir(CO_(6))_(2)(aip)]Cl(Ir2),where CO6=coumarin 6,dppz=dipyrido[3,2-a:2’,3’-...Herein,we have designed,synthesized,and characterized two novel coumarin-6-based Ir(Ⅲ)photo-catalysts viz.[Ir(CO_(6))_(2)(dppz)]Cl(Ir1)and[Ir(CO_(6))_(2)(aip)]Cl(Ir2),where CO6=coumarin 6,dppz=dipyrido[3,2-a:2’,3’-c]phenazine,and aip=2-(anthracen-9-yl)-1H-imidazo[4,5-f][1,10]phenanthroline.Coumarin 6 introduced a green light absorption property.When exposed to green light,complexes Ir1 and Ir2 demonstrated catalytic NADH photo-oxidation with a TOF of ca.840–1000 h^(−1) in PBS,comparable to or higher than the highest achieved TOF with previously reported Ir(Ⅲ)-based photo-catalysts for NADH oxidation.Ir1 and Ir2 also generated^(1)O_(2)on green light irradiation.Both the complexes showed remarkable photo-toxicities against human lung adenocarcinoma cells(A549)and human cervical cancer cells(HeLa)with the IC_(50)and PIs(dark IC_(50)/light IC_(50))in the range of 0.5–1.6μM and>28–71,respectively.Interestingly,these complexes did not show any notable toxicities toward the normal human bronchial epithelial(BEAS-2B)cell line under dark conditions.The selectivity index(SI=light IC_(50)in normal cells/light IC_(50)in cancer cells)of Ir1 and Ir2 for the killing of cancer cells was in the range of 7–19.Moreover,Ir1 and Ir2 also showed good phototoxicity against A549 cancer cells under hypoxic conditions,revealing their potential for hypoxic tumor treatment.The mechanistic investigation of the most potent complex Ir2 in A549 cells revealed that it localized in the mitochondria,generated ROS and oxidized NADH during light exposure,ultimately causing cell apoptosis via mitochondrial depolarization.This strategy of killing cancer cells by combining type-Ⅰ and type-Ⅱ mechanisms,i.e.via NADH oxidation,H2O2,•OH,and 1O2 generation,could provide efficient photo-activated chemotherapy.展开更多
基金We thank BRNS(54/14/08/2022-BRNS-R),the Government of India,for financial support.
文摘Herein,we have designed,synthesized,and characterized two novel coumarin-6-based Ir(Ⅲ)photo-catalysts viz.[Ir(CO_(6))_(2)(dppz)]Cl(Ir1)and[Ir(CO_(6))_(2)(aip)]Cl(Ir2),where CO6=coumarin 6,dppz=dipyrido[3,2-a:2’,3’-c]phenazine,and aip=2-(anthracen-9-yl)-1H-imidazo[4,5-f][1,10]phenanthroline.Coumarin 6 introduced a green light absorption property.When exposed to green light,complexes Ir1 and Ir2 demonstrated catalytic NADH photo-oxidation with a TOF of ca.840–1000 h^(−1) in PBS,comparable to or higher than the highest achieved TOF with previously reported Ir(Ⅲ)-based photo-catalysts for NADH oxidation.Ir1 and Ir2 also generated^(1)O_(2)on green light irradiation.Both the complexes showed remarkable photo-toxicities against human lung adenocarcinoma cells(A549)and human cervical cancer cells(HeLa)with the IC_(50)and PIs(dark IC_(50)/light IC_(50))in the range of 0.5–1.6μM and>28–71,respectively.Interestingly,these complexes did not show any notable toxicities toward the normal human bronchial epithelial(BEAS-2B)cell line under dark conditions.The selectivity index(SI=light IC_(50)in normal cells/light IC_(50)in cancer cells)of Ir1 and Ir2 for the killing of cancer cells was in the range of 7–19.Moreover,Ir1 and Ir2 also showed good phototoxicity against A549 cancer cells under hypoxic conditions,revealing their potential for hypoxic tumor treatment.The mechanistic investigation of the most potent complex Ir2 in A549 cells revealed that it localized in the mitochondria,generated ROS and oxidized NADH during light exposure,ultimately causing cell apoptosis via mitochondrial depolarization.This strategy of killing cancer cells by combining type-Ⅰ and type-Ⅱ mechanisms,i.e.via NADH oxidation,H2O2,•OH,and 1O2 generation,could provide efficient photo-activated chemotherapy.
