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

The synthesis and characterization of a series of heteroleptic ruthenium(II) dyads derived from pyrrole-2-carboxylate 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, whereupon 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 selectivit...