title: Ruthenium(II) arene PTA (RAPTA) complexes: impact of enantiomerically pure chiral ligands.
abstract: Organometallic ruthenium(II) arene complexes containing the PTA ligand ([Ru(η(6)-arene)Cl(2)(PTA)], PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane, termed RAPTA) show pharmacologically relevant anti-tumour properties in vitro. Two new enantiomeric pairs of RAPTA compounds, containing the chiral arene (R)- or (S)-2-phenyl-N-(1-phenylethylene)acetamide and either dichlorido or oxalato ligands were synthesised and fully characterised. The stability of the complexes towards hydrolysis was assessed and the dichlorido complexes were found to be more stable towards hydrolysis than the prototype complex RAPTA-C, ([Ru(η(6)-p-cymene)Cl(2)(PTA)]). The cytotoxicity of the compounds towards human ovarian cancer cells is moderate to good with a degree of selectivity towards the cancer cells over healthy cells. More significantly, for the first time we were able to establish the influence of a bulky, chiral group attached to the arene on the cytotoxicity of this class of compound, with the S-enantiomer being more cytotoxic than the R-enantiomer.
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: Shona M
authors.initials: SM
authors.lastname: Cammack
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Clavel
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dyson
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000081007:Cymenes; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D006868:Hydrolysis; D008024:Ligands; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D000081007:Cymenes; D008024:Ligands; D009942:Organometallic Compounds; C530402:dichloro(4-cymene)(1,3,5-triaza-7-phosphatricyclo(3.3.1.1)decane)ruthenium(II)