New Ru^IIpincer 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)(Phphen)(3,5-(NO)pcyd)], 1, [Ru(L)(Mephen)(3,5-(NO)pcyd)], 2, and [Ru(L)(Clphen)(3,5-(NO)pcyd)], 3 (HL: 5-methoxy-1,3-bis(1-methyl-1H-benzo[d]imidazol-2-yl)benzene, 3,5-(NO)pcyd: 3,5-(NO)pcyd, Phphen: 4,7-diphenyl-1,10-phenanthroline, Mephen: 4,7-dimethyl-1,10-phenanthroline, Clphen: 4,7-dichloro-1,10-phenanthroline) have been synthesized and studied as potential photosensitizers (PSs) in photodynamic therapy (PDT). The complexes exhibited promising O 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 (O) 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 (IC > 300 μM) and, remarkably, on non-cancerous MRC-5 cells (IC > 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.

Novel Cyclometalated Fe(II) Complex with NCN Pincer and BODIPY‐Appended 4'‐Ethynyl‐2,2':6',2”‐terpyridine as Mitochondria‐Targeted Photodynamic Anticancer Agents

“…The complex 1 has Φ ( 1 O 2 ) value of 68% in acetonitrile (500 nm, direct method). The obtained value for 1 in acetonitrile is comparable with 1 O 2 quantum yields reported for related compounds [48b,49–51] . These data exhibit that the complex 1 has a great efficacy in the photosensitization of molecular oxygen.…”

“…The luminescence lifetime of complex 1 is 624 ns. This complex has higher quantum yields and longer lifetimes than [Ru(bpy) 3 ] 2+ and Ru(II) pincer complexes [46,48b] …”

“…Thus, the determination of 1 O 2 quantum yields of complex 1 was made upon irradiation at 500 nm (Table S1). The 1 O 2 photosensitizing properties of 1 were considered by direct and indirect measurement [48b] …”

“…The singlet oxygen quantum yields were measured by two different methods, direct and indirect evaluation, as previously reported [48b] …”

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

“…The compounds showed high uptake and effective photocytotoxicity in HeLa cells under light irradiation (350 nm) with the formation of 1 O 2 and hydroxyl radicals. 263 …”