New RuII pincer complexes: synthesis, characterization and biological evaluation for photodynamic therapy

Abstract

Three new ruthenium(II) complexes of NCN pincer and phenylcyanamide derivative ligands of the formula [Ru(L)(Ph₂phen)(3,5-(NO₂)₂pcyd)], 1, [Ru(L)(Me₂phen)(3,5-(NO₂)₂pcyd)], 2, and [Ru(L)(Cl₂phen)(3,5-(NO₂)₂pcyd)], 3 (HL: 5-methoxy-1,3-bis(1-methyl-1H-benzo[d]imidazol-2-yl)benzene, 3,5-(NO₂)₂pcyd: 3,5-(NO₂)₂pcyd, Ph₂phen: 4,7-diphenyl-1,10-phenanthroline, Me₂phen: 4,7-dimethyl-1,10-phenanthroline, Cl₂phen: 4,7-dichloro-1,10-phenanthroline) have been synthesized and studied as potential photosensitizers (PSs) in photodynamic therapy (PDT). The complexes exhibited promising ¹O₂ production quantum yields comparable with PSs available on the market. The DNA-binding interactions of the complexes with calf thymus DNA have been studied by absorption, emission, and viscosity measurements. All complexes cleave SC-DNA efficiently on photoactivation at 350 nm with the formation of singlet oxygen (¹O₂) and hydroxyl radicals (˙OH) in type-II and photoredox pathways. Complexes 1–3 showed very good uptake in cervical cancer cells (HeLa). The compounds studied were found to exhibit low toxicity against HeLa cells (IC₅₀ > 300 μM) and, remarkably, on non-cancerous MRC-5 cells (IC₅₀ > 100 μM) in the dark. However, 1 showed very promising behavior with an increment of about 90 times, in its cytotoxicity upon light illumination at 420 nm in addition to very good human plasma stability.