Photoactivatable Organometallic Pyridyl Ruthenium(II) Arene Complexes

Abstract

The synthesis and characterization of a family of piano-stool Ru II arene complexes of the type [(η 6 -arene)Ru(N,N′)(L)][PF 6 ] 2, where arene is p -cymene ( p -cym), hexamethylbenzene (hmb), or indane (ind), 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 [(η 6 - p -cym)Ru(bpm)(4-MePy)] 2+ ( 2 ), [(η 6 - p -cym)Ru(bpm)(4-BzPy)] 2+ ( 6 ), [(η 6 - p -cym)Ru(bpm)(trz)] 2+ ( 7 ), [(η 6 - p -cym)Ru(phen)(Py)] 2+ ( 10 ), and [(η 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 [(η 6 -arene)Ru(N,N′)(OH 2 )] 2+ that otherwise would not form in the dark. The photoproducts were characterized by UV–vis absorption and 1 H 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 Ru II pyridine complexes follow a relatively similar photochemical L-ligand dissociation mechanism, likely to occur from a series of 3 MC 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 Ru II arene complexes [(η 6 - p -cym)Ru(bpm)(Py)] 2+ ( 1 ), [(η 6 - p -cym)Ru(bpm)(4-MeOPy)] 2+ ( 3 ), [(η 6 - p -cym)Ru(4,4′-bpy)] 2+ ( 4 ), [(η 6 -hmb)Ru(bpm)(Py)] 2+ ( 8 ), [(η 6 -ind)Ru(bpm)(Py)] 2+ ( 9 ), [(η 6 - p -cym)Ru(phen)(Py)] 2+ ( 10 ), [(η 6 - p -cym)Ru(bathophen)(Py)] 2+ ( 12 ), [(η 6 - p -cym)Ru(bpm)(NA)] 2+ ( 15 ), and [(η 6 - p -cym)Ru(bpm)(MN)] 2+ ( 16 ) were cytotoxic toward A2780 human ovarian cancer cell line in the absence of photoirradiation (IC 50 values in the range of 9.0–60 μM).