Highly Efficient Ir(III)-Coumarin Photo-Redox Catalyst for Synergetic Multi-Mode Cancer Photo-Therapy

Abstract

Four photo-catalysts of the general formula [Ir(CO6/ppy)2(L)]Cl where CO6=coumarin 6 (Ir1–Ir3), ppy=2-phenylpyridine (Ir4), L=4′-(3,5-di-tert-butylphenyl)-2,2′ : 6′,2′′-terpyridine (Ir1), 4′-(3,5-bis(trifluoromethyl)phenyl)-2,2′ : 6′,2′′-terpyridine (Ir2 and Ir4), and 4-([2,2′ : 6′,2′′-terpyridin]-4′-yl)-N,N-dimethylaniline (Ir3) were synthesized and characterized. These photostable photo-catalysts (Ir1–Ir3) showed strong visible light absorption between 400–550 nm. Upon light irradiation (465 and 525 nm), Ir1–Ir3 generated singlet oxygen and induced rapidly photo-catalytic oxidation of cellular coenzymes NAD(P)H. Ir1–Ir3 showed time-dependent cellular uptake with excellent intracellular retention efficiency. Upon green light irradiation (525 nm), Ir2 provided a much higher photo-index (PI=793) than the clinically used photosensitizer, 5-aminolevulinicacid (5-ALA, PI>30) against HeLa cancer cells. The observed necro-apoptotic anticancer activity of Ir2 was due to the Ir2 triggered photo-induced intracellular redox imbalance (by NAD(P)H oxidation and ROS generation) and change in the mitochondrial membrane potential. Remarkably, Ir2 showed in vivo photo-induced catalytic anticancer activity in mouse models. © 2021 Wiley-VCH GmbH.