Turning the Spotlight Away from PDT: Chemodynamic Dominance of 2-(2-Bromopyridin-4-yl)-1H-imidazo[4,5-f][1,10]phenanthroline Based Ru(II)/Ir(III)/Re(I) Complexes against MDA-MB-231.

A series of ruthenium(II), iridium(III), and rhenium(I) complexes incorporating a 2-bromopyridine imidazophenanthroline ligand were synthesized and initially poised as photodynamic therapy candidates, supported by TD-DFT and excited-state lifetime data. Interestingly, cytotoxicity studies in triple negative cancer cells (MDA-MB-231) showed only marginal light-induced effects and low phototoxicity index values; the photodynamic therapeutic potential fell short. In contrast, the ruthenium complex [RuL] delivered striking anticancer activity in the dark, marking a clear shift toward chemodynamic therapy. Ruthenium complexes induced robust ROS generation, mitochondrial membrane disruption, and intrinsic apoptosis, all independent of light. Its mitochondrial localization, G0/G1 arrest, and gene modulation (↑TP53, ↑BAX, and ↓BCL-2) confirmed a mitochondria-targeted CDT mechanism.