A water-soluble photolabile ruthenium(ii) complex with a terpyridyl-dicarboxylate ligand: photocytotoxicity triggered by structural strain

Abstract

Structural distortions from the ideal octahedral geometry are known to facilitate the photorelease of kinetically inert groups in Ru(II) polypyridyl complexes. Building on this principle, here we report, for the first time, the design of a water-soluble Ru(II) complex containing a terpyridine-dicarboxylate pentadentate ligand (LH₂), formulated as [Ru{ptpy(COO⁻)₂}(DMSO)] (RuL), engineered for efficient photorelease of the bound monodentate DMSO ligand in aqueous medium. This work presents a novel idea for inducing axial Ru–DMSO bond photolability from the conformational strain originating from a pentadentate ligand in an Ru(II) complex, triggering photodissociation to create potent cytotoxic species for phototherapeutic application. The molecular identity, and photophysical and electrochemical features with 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 photo-activated chemotherapeutic (PACT) uses. The geometry-optimized structure and the nature of the frontier molecular orbitals have been determined using DFT calculations. The photosubstitution quantum yield (Φ_PS) in acetonitrile was thirteen times greater than that in water, highlighting the significant influence of solvent on the photochemical efficiency. Notably, the RuL ligand exhibited substantial cytotoxicity under light irradiation, while remaining non-cytotoxic in the dark, underscoring its potential utility in Ru(II)-based photo-activated chemotherapy.