Marked Improvement in Photoinduced Cell Death by a New Tris-heteroleptic Complex with Dual Action: Singlet Oxygen Sensitization and Ligand Dissociation

The new tris-heteroleptic complex [Ru(bpy)(dppn)(CH3CN)(2)](2+) (3, bpy = 2,2'-bipyridine, dppn = benzo[i]dipyrido[3,2-a;2',3'-c]phenazine) was synthesized and characterized in an effort to generate a molecule capable of both singlet oxygen (O-1(2)) production and ligand exchange upon irradiation. Such dual reactivity has the potential to be useful for increasing the efficacy of photochemotherapy drugs by acting via two different mechanisms simultaneously. The photochemical properties and photoinduced cytotoxicity of 3 were compared to those of [Ru(bpy)(2)(dppn)](2+) (1) and [Ru(bpy)(2)(CH3CN)(2)](2+) (2), since 1 sensitizes the production of O-1(2) and 2 undergoes ligand exchange of the monodentate CH3CN ligands with solvent when irradiated. The quantum yield of O-1(2) production was measured to be 0.72(2) for 3 in methanol, which is slightly lower than that of 1, F = 0.88(2), in the same solvent (lambda irr = 460 nm). Complex 3 also undergoes photoinduced ligand exchange when irradiated in H2O (lambda irr = 400 nm), but with a low quantum efficiency (<1%). These results are explained by the presence of the low-lying ligand-centered (3)pp* excited state of 3 localized on the dppn ligand, thus decreasing the relative population of the higher energy (3)dd state; the latter is associated with ligand dissociation. Cytotoxicity data with HeLa cells reveal that complex 3 exhibits a greater photocytotoxicity index, 1110, than does either 1 and 2, indicating that the dual-action complex is more photoactive toward cells in spite of its low ligand exchange quantum yield.