Instigating Visible Light Inspired DNA Impairment by ROS Harvesting Ir(III)-Cyclometallated Imidazophenanthroline Complexes Against MDA-MB-231 Cells

Abstract

Difficulties to abate the vehemence of deleterious triple-negative breast cancer (TNBC) is an ardent issue in the current context of anticancer research due to the lack of a selective treatment modality. To address this issue, herein we have endeavored to establish the imidazophenanthroline-based Ir(III)-cyclometallated heteroleptic complexes, suited for the one-photon photodynamic therapy (OP-PDT) under irradiation of visible light (400–700 nm) possessing long-lived excited triplet state and significant photostability. Among three synthesized complexes, [L1Ir], [L2Ir], [L3Ir], the complex [L2Ir] has been recognized as the most competent complex to exhibit selective phototoxicity (IC₅₀=3.8 μM; PI^c=78.94) in MDA-MB-231 triple-negative breast cancer cells. The significant phototoxicity of the complexes has arisen due to the production of reactive singlet oxygen (¹O₂) following the type-II pathway (Φ_s=0.26). Also, the complexes have shown the proficiency in oxidation of reduced nicotinamide adenine dinucleotide (NADH) (TOF=37.82 h⁻¹) indicating the possibility of reactive oxygen species (O₂⋅⁻, ⋅OH) generation through type-I pathway upon visible light irradiation. Along with this, intracellular glutathione (GSH) depletion capabilities have endued the complexes to unarm the TNBC cells in front of the profuse amount of ROS instigating the programmed cell death (PCD) through substantial DNA damage.