Cytotoxicity Studies of Cyclometallated Ruthenium(II) Compounds: New Applications for Ruthenium Dyes

The antiproliferative activity of four Ru­(II) dyes incorporating the cyclometallated ligand phpy^– (deprotonated 2-phenylpyridine) have been tested against HeLa cells. All of the compounds exhibit cytotoxic activity similar to that of cisplatin. The most active compound, [Ru­(phpy)­(bpy)­(dppn)]⁺ (<b>4</b>; bpy = 2,2′-bipyridine, dppn = benzo­[<i>i</i>]­dipyrido­[3,2-<i>a</i>:2′,3′-<i>c</i>]­phenazine), is 6 times more active than the platinum drug, and it is able to disrupt the mitochondria membrane potential. In addition, [Ru­(phpy)­(biq)₂]⁺ (<b>3</b>; biq = 2,2′-biqinoline), with strong absorption at 640 nm, exhibits enhanced activity upon irradiation with 633 nm light. These findings demonstrate that coordinatively saturated cyclometallated Ru dyes have the potential to emerge as a new family of organometallic anticancer compounds, both in the dark and upon irradiation with low-energy light. The compound [Ru­(phpy)­(pap)­(NCCH₃)₂]⁺ (<b>5</b>; pap = 2-(phenylazo)­pyridine) was also synthesized and structurally characterized as a new precursor for the preparation of tris-heteroleptic dyes