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

Abstract

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)]+ (4; bpy = 2,2′-bipyridine, dppn = benzo[i]dipyrido[3,2-a:2′,3′-c]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]+ (3; 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]+ (5; pap = 2-(phenylazo)pyridine) was also synthesized and structurally characterized as a new precursor for the preparation of tris-heteroleptic dyes.