Trifluoromethyl substitution enhances photoinduced activity against breast cancer cells but reduces ligand exchange in Ru(ii) complex.

A series of five ruthenium complexes containing triphenyl phosphine groups known to enhance both cellular penetration and photoinduced ligand exchange, -[Ru(bpy)(P(-R-Ph))(CHCN)], where bpy = 2,2'-bipyridine and P(-R-Ph) represent -substituted triphenylphosphine ligands with R = -OCH (), -CH () -H (), -F (), and -CF (), were synthesized and characterized. The photolysis of in water with visible light ( ≥ 395 nm) results in the substitution of the coordinated acetonitrile with a solvent molecule, generating the corresponding aqua complex as the single photoproduct. A 3-fold variation in quantum yield was measured with 400 nm irradiation, , where is the most efficient with a = 0.076(2), and the least photoactive complex, with = 0.026(2). This trend is unexpected based on the red-shifted metal-to-ligand charge transfer (MLCT) absorption of as compared to that of , but can be correlated to the substituent Hammett parameters and p values of the ancillary phosphine ligands. Complexes are not toxic towards the triple negative breast cancer cell line MDA-MB-231 in the dark, but and are >4.2 and >19-fold more cytotoxic upon irradiation with blue light, respectively. A number of experiments point to apoptosis, and not to necrosis or necroptosis, as the mechanism of cell death by upon irradiation. These findings provide a foundation for understanding the role of phosphine ligands on photoinduced ligand substitution and show the enhancement afforded by -CF groups on photochemotherapy, which will aid the future design of photocages for photochemotherapeutic drug delivery.