Photoactivatable Organometallic Pyridyl Ruthenium(II) Arene Complexes

The synthesis and characterization of a family of piano-stool Ru-II arene complexes of the type [(eta(6)-arene)Ru(N,N')(L)][PF6](2), where arene is p-cymene (p-cym), hexamethylbenzene (limb), or indane (id), N,N' is 2,2'-bipyrimidine (bpm), 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione (phendio), or 4,7-diphenyl-1,10-phenanthroline (bathophen), and L is pyridine (Py), 4-methylpyridine (4-MePy), 4-methoxypyridine (4-MeOPy), 4,4'-bipyridine (4,4'-bpy), 4-phenylpyridine (4-PhPy), 4-benzylpyridine (4-BzPy), 1,2,4-triazole (trz), 3-acetylpyridine (3-AcPy), nicotinamide (NA), or methyl nicotinate (MN), are reported, including the X-ray crystal structures of [(eta(6)-p-cym)Ru(bpm)(4-MePy)](2+) (2), [(eta(6)-p-cym)Ru(bpm)(4-BzPY)](2+) (6), [(eta(6)-p-cym)Ru(bpm)(trz)](2+) (7), [(eta(6)-p-cym)Ru(phen)(Py)](2+) (10), and [(eta(6)-ind)Ru(bpy)(Py)](2+) (13). These complexes can selectively photodissociate the monodentate ligand. (L) when excited with UVA or white light, allowing strict control of the formation of the reactive aqua species [(eta(6)-arene)Ru(N,N')(OH2)](2+) that otherwise would not form in the dark. The photoproducts were characterized by UV-vis absorption and H-1 NMR spectroscopy. DFT and TD-DFT calculations were employed to characterize the excited states and to obtain information on the photochemistry of the complexes. All the Run pyridine complexes follow a relatively similar photochemical L-ligand dissociation mechanism, likely to occur from a series of (MC)-M-3 triplet states with dissociative character. The photochemical process proved to be much more efficient when UVA-range irradiation was used. More strikingly, light activation was used to phototrigger binding of these potential anticancer agents with discriminating preference toward 9-ethylguanine (9-EtG) over 9-ethyladenine (9-EtA). Calf thymus (CT)-DNA binding studies showed that the irradiated complexes bind to CT-DNA, whereas the nonirradiated forms bind negligibly. Studies of CT-DNA interactions in cell-free media suggest combined weak monofunctional coordinative and intercalative binding modes. The Run arene complexes [(eta(6)-p-cym)Ru(bpm)(Py)](2+) (1), [(eta(6)-p-cym)Ru(bpm)(4-MeOPy)](2+) (3), [(eta(6)-p-cym)Ru(4,4'-bpy)](2+) (4), [(eta(6)-hmb)Ru(bpm)(Py)](2+) (8), [(eta(6)-ind)Ru(bpm)(Py)](2+) (9), [(eta(6)-p-cym)Ru(phen)(Py)](2+) (10), [(eta(6)-p-cym)Ru(bathophen)-(Py)](2+) (12), [(eta(6)-p-cym)Ru(bpm)(NA)](2+) (15), and [(eta(6)-p-cym)Ru(bpm)(MN)](2+) (16) were cytotoxic toward A2780 human ovarian cancer cell line in the absence of photoirradiation (IC50 values in the range of 9.0-60 mu M).