title: Ruthenium(II) and osmium(II) 1,2,3-triazolylidene organometallics: a preliminary investigation into the biological activity of 'click' carbene complexes.
abstract: Taking advantage of the facile and versatile synthetic properties of 'click' 1,2,3-triazolylidene N-heterocyclic carbenes (tzNHC's), a range of new organometallic Ru(II) and Os(II) arene complexes containing functionalised tzNHC ligands, [M(η(6)-p-cymene)(tzNHC)Cl2] [M = Ru(II), Os(II)], have been synthesised and fully characterised, including the X-ray crystal structure of one of the Os(II) complexes. The tzNHC ligands remain coordinated to the metal centres under relevant physiological conditions, and following binding to the model protein, ubiquitin. The in vitro cytotoxicity of the compounds towards human ovarian cancer cells is dependent on the substituent on the tzNHC ligand but is generally <50 μM and in some cases <1 μM, whilst still retaining a high degree of selectivity towards cancer cells over healthy cells (1.85 μM in A2780 ovarian cancer cells versus 435 μM in human embryonic kidney cells in one case).
authors.affiliation: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Kilpin
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Crot
authors.forename: Tina
authors.initials: T
authors.lastname: Riedel
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Kitchen
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dyson
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D018360:Crystallography, X-Ray; D057809:HEK293 Cells; D006801:Humans; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D008968:Molecular Conformation; D009992:Osmium / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D014230:Triazoles / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D014230:Triazoles; C030011:carbene; D009992:Osmium; D012428:Ruthenium; D008697:Methane