The Role of Ancillary Ligands on Benzodipyridophenazine Based Ru(II)/Ir(III) Complexes for Dark and Light Toxicity against TNBC Cells¥

Abstract

The study investigated the impact of benzodipyridophenazine-based Ru(II) and Ir(III) complexes (Ru1, Ru2, Ir1, and Ir2) on their anticancer activity. Metal complexes displayed three significant absorption bands because of intra-ligand charge transfer (ILCT), ligand-to-ligand charge transfer (LLCT), and metal-to-ligand charge transfer (MLCT). Binding studies with biomolecules has been performed with the complexes along with the ligand, and it was found that after attaching with Ru(II)/Ir(III),properties of the ligands has enhanced. In vitro, screening identified that, complex [(η5-Cp*)IrIIICl(κ2-N, N-benzo[i]dipyrido[3,2-a:2',3'-c])phenazine (Ir1) exhibited the highest potency and selectivity (IC50 ~ 2.14 µM, PI > 13) under yellow light irradiation. The photo-toxicity trend was Ir1>Ru1>Ir2>>Ru2, which was found to be directly correlated with the release of singlet oxygen quantum yield (1O2). Chloro-substituted complexes (Ir1, Ru1) are effective for hypoxic tumor treatment, particularly Ir1 which can generate high amounts of reactive oxygen species (ROS, Type I PDT) in cells under photo irradiation. The high value of fluorescence quantum yield (fφ = 0.26) and significant emission at λ = 571 nm of Ir1 certainly helps in a bio-imaging application. Colocalisation study and DCFDA studies with Ir1 revealed that, it can accumulates in the mitochondria, leading to the depolarization of the mitochondrial membrane. These studies confirms the complex Ir1 is a promising candidate for TNBC treatment in hypoxic tumors, with efficacy comparable to the current PDT drug, photofrin.