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

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)]Cl-2 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 (MLCT)-M-3 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 mu M with PI values as high as >200 vs. MCF7. Computational studies were used to predict the energies of the (MLCT)-M-3 and (MC)-M-3 states. An inaccessible (MC)-M-3 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 (MLCT)-M-3 state for O-1(2) generation explains the excellent photocytotoxicity of 2.