New RuIIpincer complexes: synthesis, characterization and biological evaluation for photodynamic therapy.
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 promising1O2production 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.
Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111, Iran. l.tabrizi@ch.iut.ac.ir Chinif@cc.iut.ac.ir.
Leila
L
Tabrizi
Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111, Iran. l.tabrizi@ch.iut.ac.ir Chinif@cc.iut.ac.ir.
Hossein
H
Chiniforoshan
D000818:Animals; D001554:Benzene / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D004705:Endocytosis; D006367:HeLa Cells; D006801:Humans; D008027:Light; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010618:Phenanthrolines / Q000737:chemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology; D026082:Singlet Oxygen / Q000737:chemistry
D009942:Organometallic Compounds; D010618:Phenanthrolines; D017319:Photosensitizing Agents; D026082:Singlet Oxygen; D012428:Ruthenium; D004247:DNA; D001554:Benzene; C025205:1,10-phenanthroline