Benzothiophenyl-Imidazophenanthroline-Based Ru(II) and Ir(III) Half-Sandwich Complexes Induce Mitochondrial ROS-Mediated Apoptosis for Dual Chemotherapy and Photodynamic Therapy against MDA-MB-231 Breast Cancer Cells

Benzothiophene-conjugated imidazophenanthroline-based Ru(II) and Ir(III) complexes, ruthenium (RuL) and iridium (IrL), were synthesized, and their toxicity under dark and light conditions was assessed in the MDA-MB-231 cell line. Preliminary investigations of singlet-state lifetime measurements, time-resolved phosphorescence decay studies, and time-dependent density functional theory corroborate the photodynamic characteristics of the complexes. Furthermore, investigations involving reactive oxygen species with various agents (DPBF, NADH, methylene blue, and TMB) demonstrate that these complexes can participate in both Type I and Type II pathways crucial for photodynamic treatment. Cytotoxicity studies demonstrated light-induced cytotoxic effects against the MDA-MB-231 cell line, with RuL showing significant phototoxicity (phototoxicity index (PI) = 5.1), which is >3-fold higher than that of IrL (PI = 1.4). Furthermore, biological investigations revealed the mitochondrial colocalization of both RuL and IrL, with RuL exhibiting enhanced mitochondrial colocalization when subjected to light irradiation. Complex RuL furthermore induced depolarization of the mitochondrial membrane and selectively promoted cell cycle arrest at the G2/M phase.