Photoactivatable Organometallic Pyridyl Ruthenium(II) Arene Complexes

The synthesis and characterization of a family of piano-stool
RuII arene complexes of the type [(η6-arene)­Ru­(N,N′)­(L)]­[PF6]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 [(η6-p-cym)­Ru­(bpm)­(4-MePy)]2+ (2), [(η6-p-cym)­Ru­(bpm)­(4-BzPy)]2+ (6), [(η6-p-cym)­Ru­(bpm)­(trz)]2+ (7), [(η6-p-cym)­Ru­(phen)­(Py)]2+ (10), and [(η6-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 [(η6-arene)­Ru­(N,N′)­(OH2)]2+ that otherwise would not form in the dark.
The photoproducts were characterized by UV–vis absorption and 1H 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 RuII pyridine
complexes follow a relatively similar photochemical L-ligand dissociation
mechanism, likely to occur from a series of 3MC 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 RuII arene
complexes [(η6-p-cym)­Ru­(bpm)­(Py)]2+ (1), [(η6-p-cym)­Ru­(bpm)­(4-MeOPy)]2+ (3), [(η6-p-cym)­Ru­(4,4′-bpy)]2+ (4), [(η6-hmb)­Ru­(bpm)­(Py)]2+ (8), [(η6-ind)­Ru­(bpm)­(Py)]2+ (9), [(η6-p-cym)­Ru­(phen)­(Py)]2+ (10), [(η6-p-cym)­Ru­(bathophen)­(Py)]2+ (12), [(η6-p-cym)­Ru­(bpm)­(NA)]2+ (15), and [(η6-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 μM).