title: Bis-picolinamide Ruthenium(III) Dihalide Complexes: Dichloride-to-Diiodide Exchange Generates Single trans Isomers with High Potency and Cancer Cell Selectivity.
abstract: A library of new bis-picolinamide ruthenium(III) dihalide complexes of the type [RuX2L2] (X=Cl or I, L=picolinamide) have been synthesised and characterised. The complexes exhibit different picolinamide ligand binding modes, whereby one ligand is bound (N,N) and the other bound (N,O). Structural studies revealed a mixture of cis and trans isomers for the [RuCl2L2] complexes but upon a halide exchange reaction to yield [RuI2L2], only single trans isomers were detected. High cytotoxic activity against human cancer cell lines was observed, with the potencies of some complexes similar to or better than cisplatin. The conversion to [RuI2L2] substantially increased the activity towards cancer cell lines by more than twelvefold. The [RuI2L2] complexes displayed potent activity against the A2780cis (cisplatin-resistant human ovarian cancer) cell line, with a more than fourfold higher potency than cisplatin. Equitoxic activity was observed against normoxic and hypoxic cancer cells, which indicates the potential to eradicate both the hypoxic and aerobic fractions of solid tumours with similar efficiency. The activity of selected complexes against non-cancer ARPE-19 cells was also tested. The [RuI2L2] complexes were found to be more potent than the [RuCl2L2] analogues and also more selective towards cancer cells with a selectivity factor in excess of sevenfold.
authors.affiliation: School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
authors.forename: Aida M
authors.initials: AM
authors.lastname: Basri
authors.affiliation: School of Chemistry and Forensic Sciences, University of Bradford, Bradford, BD7 1DP, UK.
authors.forename: Rianne M
authors.initials: RM
authors.lastname: Lord
authors.affiliation: School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, UK.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Allison
authors.affiliation: School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rodríguez-Bárzano
authors.affiliation: School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lucas
authors.affiliation: School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
authors.forename: Felix D
authors.initials: FD
authors.lastname: Janeway
authors.affiliation: School of Physical Sciences, University of Kent, Canterbury, Kent, CT2 7NH, UK.
authors.forename: Helena J
authors.initials: HJ
authors.lastname: Shepherd
authors.affiliation: School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Pask
authors.affiliation: School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, UK.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Phillips
authors.affiliation: School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: McGowan
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000737:chemistry*; D002945:Cisplatin / Q000633:toxicity; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D018360:Crystallography, X-Ray; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D007454:Iodides / Q000737:chemistry*; D007536:Isomerism; D008024:Ligands; D008968:Molecular Conformation; D012428:Ruthenium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D002712:Chlorides; D056831:Coordination Complexes; D007454:Iodides; D008024:Ligands; D012428:Ruthenium; D002945:Cisplatin
keywords: antitumor agents; cytotoxicity; isomers; ligand effects; ruthenium