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Photoactivatable Organometallic Pyridyl Ruthenium(II) Arene Complexes

Soledad Betanzos-Lara, Luca Salassa, Abraha Habtemariam, Olga Novakova, Ana M. Pizarro, Guy J. Clarkson, Barbora Liskova, Viktor Brabec, and Peter J. Sadler.

The synthesis and characterization of a family of piano-stool Ru^II arene complexes of the type [(η⁶-arene)Ru(N,N′)(L)][PF₆]_2, 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 Ru^II 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 Ru^II arene complexes were cytotoxic toward A2780 human ovarian cancer cell line in the absence of photoirradiation (IC₅₀ values in the range of 9.0–60 μM).