Synthesis and Photobiological Activity of Ru(II) Dyads Derived from Pyrrole-2-carboxylate Thionoesters

The synthesis and characterization of a series of [GRAPHIC] heteroleptic ruthenium(II) dyads derived from pyrrole-2carboxylate thionoesters are reported. Ligands bearing a conjugated thiocarbonyl group were found to be more reactive toward Ru(II) complexation:Compared to analogous all-oxygen pyrrole-2-carboxylate esters, and salient features of the resulting complexes were determined using X-ray crystallography, electronic absorption, and NMR spectroscopy, Selected complexes were evaluated for their potential in photobiolOgical applications, where-upon all compounds demonstrated in vitro photodynamic therapy effects in HL-60 and SK-MEL-28 cells, with low nanomolar activities, observed, and exhibited some of the largest photocytotoxicity indices to date (>2000). Importantly, the Ru(II) dyads could be activated by relatively soft doses of visible (100 J cm (-2) 29 mW cm(-2)) or red light (100 J cm(-2), 34 mW cm(-2)), which is compatible with therapeutic applications. Some compounds even demonstrated up to five=fold selectivity for malignant cells over noncancerous cells. These complexes were also shown to photocleave, and in some cases unwind, DNA in cell-free-experiments. Thus, this new class of RU(II)dyads has the capacity to interact with and.damage biological macromolecules in the cell, making them attractive agents for photoclynarnic therapy.