title: Cytotoxicity of cyclometallated ruthenium complexes: the role of ligand exchange on the activity.
abstract: The cyclometallated Ru(II) complexes cis-[Ru(phpy)(phen)(CH3CN)2](PF6) (1; phpy(-)=deprotonated 2-phenylpyridine, phen=1,10-phenanthroline) and cis-[Ru(phpy)(bpy)(CH3CN)2](PF6) (2; bpy=2,2'-bipyridine) were investigated as potential agents for photodynamic therapy. The presence of phpy(-) in the coordination sphere results in a red-shift of the Ru→phen and Ru→bpy metal-to-ligand charge transfer of 1 and 2, respectively, thus improving the tissue penetration of light while maintaining the efficient photo-induced ligand exchange required for DNA binding. The 14-fold enhancement of OVCAR-5 cell death that occurs upon irradiation with 690 nm light can be attributed to photo-aquation. The role of glutathione (GSH) on the toxicity of the complex was also explored. Complexes 1 and 2 undergo ligand substitution in the presence of GSH in the dark, such that the metal may covalently bind to biomolecules. The combination of photo-induced ligand exchange and GSH-facilitated ligand exchange may explain the observed cytotoxicity.
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43214, USA.
authors.forename: Alycia M
authors.initials: AM
authors.lastname: Palmer
authors.forename: Bruno
authors.initials: B
authors.lastname: Peña
authors.forename: R Bryan
authors.initials: RB
authors.lastname: Sears
authors.forename: Olivia
authors.initials: O
authors.lastname: Chen
authors.forename: Maya
authors.initials: M
authors.lastname: El Ojaimi
authors.forename: Randolph P
authors.initials: RP
authors.lastname: Thummel
authors.forename: Kim R
authors.initials: KR
authors.lastname: Dunbar
authors.forename: Claudia
authors.initials: C
authors.lastname: Turro
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D008027:Light; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D010778:Photochemotherapy / Q000379:methods*; D012428:Ruthenium / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D012428:Ruthenium
keywords: glutathione; ligand exchange; photochemistry; photodynamic therapy; ruthenium