Light-activated cytotoxicity of dicarbonyl Ru() complexes with a benzimidazole coligand towards breast cancer

Reaction between [RuCl 2 (CO) 2 ] n and 1 H -benzimidazol-2-ylmethyl-( N -phenyl)amine ligands (L R ) functionalized with various electron-donating and electron-withdrawing substituents on the phenyl ring (R = H, 4-CH 3 , 4-Cl, 4-COOCH 3 , and 3-COOCH 3 ) afforded the dark-stable photoactivatable carbon monoxide prodrugs of the general formula [RuCl 2 (CO) 2 L R ]. Release of the CO molecules from the Ru( ii ) compounds was examined by monitoring the electronic and IR spectra upon illumination at 365 nm. A noticeable decrease in the intensities of the two characteristic ν (C&z.tbd;O) modes for Ru(CO) II 2 species, and the growth of two new bands for the mono-carbonyl species and free CO, were the main features of the photolysis profiles. The cytotoxicity of the complexes towards breast cancer (MCF-7) cells was assessed with and without illumination at 365 nm. All the complexes except that with a 4-COOCH 3 group (IC 50 = 45.08 ± 3.5 μM) are nontoxic under dark conditions. Upon illumination, all the compounds acquired cytotoxicity in the following order: H > 4-COOCH 3 > 4-CH 3 > 4-Cl > 3-COOCH 3 . Investigation of the cytotoxicity of the CO-depleted fragments showed that the light-induced cytotoxicity can be attributed to the liberated CO and CO-depleted metal fragments, including the liberated benzimidazole ligands. Upon photoinduced CO release, all the Ru( ii ) complexes acquired cytotoxicity against MCF-7 that may be attributed to the liberated CO and CO-depleted metal fragments including the liberated Coligands. Ru( ii ) complex of the unsubstituted ligand exhibited the highest activity.