Photoresponsive Ruthenium(II) Isomeric Switches in Solution: Leveraging Asymmetry in Ligand Design for Precision in Photoactivated Chemotherapy

Ligand orientation is emerging as a powerful, underexploited lever for tuning the photoreactivity of Ru(II) complexes, although its mechanistic basis remains unclear. Herein, we report a systematic isomeric series, [RuII(ptpy)(N^N)(DMSO)]2+ (ptpy = 4′-phenyl-2,2′:6′,2″-terpyridine), based on unsymmetrical picolylamine/picolylimine N^N donors, alongside the bpy-based reference complex [3]. Crystal structures of four geometrical isomers ([1]AMD, [2]AMD, [1]IMD, [2]IMD) pinpoint how donor placement, which possibly could reshape the excited-state behavior. Visible-light irradiation in acetonitrile triggers clean DMSO photosubstitution, yet the amine and imine platforms diverge sharply in outcome, giving ∼3:2 vs. 1:3 Npy-cis-MeCN:Npy-trans-MeCN product ratios. Strikingly, isomers wherein −NH2 /═NH- trans to DMSO react substantially faster despite virtually invariant Ru–DMSO bond lengths across the series, showing that kinetic control arises in the excited state, not from ground-state structural perturbation. Light drives reversible switching between geometrical isomers via a plausible common pentacoordinate intermediate, revealing previously unrecognized structural flexibility in this ligand class. TDDFT calculations assign the 1MLCT absorptions and rationalize the photosubstitution-induced red shift to selective access to dissociative 3MC states, identifying this excited-state pathway as the origin of rate differences and a predictive design principle. Collectively, these findings establish ligand orientation as a rational, structure-based handle for engineering Ru(II) excited-state reactivity, positioning this thermally robust, visible-light-responsive scaffold as a promising PACT platform.