Water-soluble photolabile ruthenium(II) complex with a terpyridyl-dicarboxylate ligand: photocytotoxicity triggered by structural strain

Abstract

Structural distortions in the excited state can facilitate the photorelease of kinetically labile groups in Ru(II) polypyridyl complexes. Leveraging on this, here we report, for the first time, the design of a water-soluble Ru(II) complex containing terpyridine-dicarboxylate pentadentate ligand (LH2), formulated [Ru{ptpy(COO-)2}(DMSO)] (RuL), engineered for efficient photosolvolyis of the bound monodentate DMSO ligand by H2O in aqueous medium. This work presents a novel idea for inducing axial Ru-L bond lability from the conformational strain originating from a pentadentate ligand in a Ru(II) complex, triggering photosolvolysis to create potent cytotoxic species for phototherapeutic application. The molecular identity, photophysical features, and solution speciation of the RuL were examined. The blue light-triggered photo substitution was studied to gain insight into potential adduct formation with biological targets relevant to photoactivated chemotherapeutic (PACT) uses. The geometry-optimized structure and the nature of the frontier molecular orbitals associated with its photo physics and photo-lability have been determined using DFT calculations. The photo-substitution quantum yield (Φ) in acetonitrile was thirteen times greater than in water, highlighting the significant influence of solvent on the photochemical efficiency. Notably, the RuL exhibited substantial cytotoxicity under blue light irradiation, while remain noncytotoxic in dark, underscoring its potential utility in Ru(II)-based photoactivated chemotherapy.