Light-responsive and Protic Ruthenium Compounds Bearing Bathophenanthroline and Dihydroxybipyridine Ligands Achieve Nanomolar Toxicity towards Breast Cancer Cells

We report new ruthenium complexes bearing the lipophilic bathophenanthroline (BPhen) ligand and dihydroxybipyridine (dhbp) ligands which differ in the placement of the OH groups ([(BPhen)₂ Ru(n,n'-dhbp)]Cl₂ with n = 6 and 4 in 1_A and 2_A , respectively). Full characterization data are reported for 1_A and 2_A and single crystal X-ray diffraction for 1_A . Both 1_A and 2_A are diprotic acids. We have studied 1_A , 1_B , 2_A , and 2_B (B = deprotonated forms) by UV-vis spectroscopy and 1 photodissociates, but 2 is light stable. Luminescence studies reveal that the basic forms have lower energy ³ MLCT states relative to the acidic forms. Complexes 1_A and 2_A produce singlet oxygen with quantum yields of 0.05 and 0.68, respectively, in acetonitrile. Complexes 1 and 2 are both photocytotoxic toward breast cancer cells, with complex 2 showing EC₅₀ light values as low as 0.50 μM with PI values as high as >200 vs. MCF7. Computational studies were used to predict the energies of the ³ MLCT and ³ MC states. An inaccessible ³ MC state for 2_B suggests a rationale for why photodissociation does not occur with the 4,4'-dhbp ligand. Low dark toxicity combined with an accessible ³ MLCT state for ¹ O₂ generation explains the excellent photocytotoxicity of 2.