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)]+ (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.