title: Hydrosulfide Adducts of Organo-Iridium Anticancer Complexes.
abstract: Novel half-sandwich hydrosulfidoiridium(III) complexes [(η(5)-Cp*)Ir(phen)(SH)]PF6 (1), [(η(5)-Cp*)Ir(bpy)(SH)]PF6 (2), [(η(5)-Cp(biph))Ir(phen)(SH)]PF6 (3), and [(η(5)-Cp(biph))Ir(bpy)(SH)]PF6 (4) were prepared from the chlorido complexes by dechlorination and treatment with excess NaSH·xH2O; phen = 1,10-phenanthroline, bpy = 2,2'-bipyridine, Cp* = 1,2,3,4,5-pentamethylcyclopentadienyl, and Cp(biph) = 1,2,3,4-tetramethyl-5-biphenylcyclopentadienyl. Complexes 1-4 were characterized by various techniques including electrospray ionization mass spectrometry, NMR spectroscopy (δ(SH) ca. -2 ppm), and a single-crystal X-ray analysis. Complex [(η(5)-Cp*)Ir(phen)(SH)]BPh4 (1') shows a typical piano-stool geometry with Ir-S bond length of 2.388(2) Å. Cp(biph) complexes 3 (IC50 = 0.98 μM) and 4 (IC50 = 0.61 μM) showed significantly higher (p < 0.005) in vitro antiproliferative activity against A2780 human ovarian cancer cells, as compared with their Cp* analogues 1 (IC50 = 49.5 μM) and 2 (IC50 = 48.4 μM), and potency similar to the anticancer drug cisplatin. The complexes were relatively stable in aqueous solution toward hydrolysis and reactions with reduced glutathione (GSH), 9-ethylguanine, or 9-methyladenine. Interestingly, GSH was readily oxidized to glutathione disulfide in the presence of Cp(biph) complexes 3 and 4, as judged by (1)H NMR, perhaps indicative of a possible redox-linked mechanism of action.
authors: Regional Centre of Advanced Technologies and Materials, Department of Inorganic Chemistry, Faculty of Science, Palacký University , 17. listopadu 12, 77146 Olomouc, Czech Republic.|Department of Chemistry, University of Warwick , Gibbet Hill Road, Coventry CV4 7AL, U. K.
authors: Pavel
authors: P
authors: Štarha
authors: Department of Chemistry, University of Warwick , Gibbet Hill Road, Coventry CV4 7AL, U. K.
authors: Abraha
authors: A
authors: Habtemariam
authors: Department of Chemistry, University of Warwick , Gibbet Hill Road, Coventry CV4 7AL, U. K.
authors: Isolda
authors: I
authors: Romero-Canelón
authors: Department of Chemistry, University of Warwick , Gibbet Hill Road, Coventry CV4 7AL, U. K.
authors: Guy J
authors: GJ
authors: Clarkson
authors: Department of Chemistry, University of Warwick , Gibbet Hill Road, Coventry CV4 7AL, U. K.
authors: Peter J
authors: PJ
authors: Sadler
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000737:chemistry*; D007495:Iridium / Q000737:chemistry*; D009930:Organic Chemicals / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D009930:Organic Chemicals; D007495:Iridium; D006862:Hydrogen Sulfide