title: Synthesis, molecular structure, computational study and in vitro anticancer activity of dinuclear thiolato-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) complexes.
abstract: Neutral dinuclear dithiolato-bridged pentamethylcyclopentadienyl Rh(III) complexes of the type (C5Me5)2Rh2(μ-SR)2Cl2 (R = CH2Ph, 1; R = CH2CH2Ph, 2) and cationic dinuclear trithiolato-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) complexes of the type [(C5Me5)2M2(μ-SR)3](+) (M = Rh, R = CH2Ph, 3; M = Rh, R = CH2CH2Ph, 5; M = Rh, R = CH2C6H4-p-(t)Bu, 7: M = Ir, R = CH2Ph, 4; M = Ir, R = CH2CH2Ph, 6; M = Ir, R = CH2C6H4-p-(t)Bu, 8) have been synthesized from the chloro-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) dimers (C5Me5)2M2(μ-Cl)2Cl2 by reaction with the corresponding thiol derivative (RSH). Complexes 3-8 were isolated as chloride salts. All complexes were obtained in good yield and were fully characterized by spectroscopic methods. The molecular structures of the neutral complexes (1 and 2) show interesting features: the two rhodium atoms are bridged by two thiolato ligands with no metal-metal bonds and the pentamethylcyclopentadienyl and chlorido ligands are oriented syn to each other, an uncommon conformation for such dinuclear complexes. These structural features were rationalized using DFT calculations. Additionally, the antiproliferative activity of the complexes was evaluated against the cancerous A2780 (cisplatin sensitive) and A2780cisR (cisplatin resistant) human ovarian cell lines and on the noncancerous HEK293 human embryonic kidney cells. All complexes were found to be active and the cationic iridium complexes , and are particularly cytotoxic, with IC50 values in the nanomolar range (IC50 < 0.1 μM). The catalytic activity of the complexes for the oxidation of glutathione (GSH) to GSSG was evaluated by NMR spectroscopy.
authors.affiliation: Institute of Chemistry, University of Neuchatel, Ave de Bellevaux 51, CH-2000 Neuchatel, Switzerland. bruno.therrien@unine.ch.
authors.forename: Gajendra
authors.initials: G
authors.lastname: Gupta
authors.forename: Amine
authors.initials: A
authors.lastname: Garci
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Murray
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dyson
authors.forename: Gabin
authors.initials: G
authors.lastname: Fabre
authors.forename: Patrick
authors.initials: P
authors.lastname: Trouillas
authors.forename: Federico
authors.initials: F
authors.lastname: Giannini
authors.forename: Julien
authors.initials: J
authors.lastname: Furrer
authors.forename: Georg
authors.initials: G
authors.lastname: Süss-Fink
authors.forename: Bruno
authors.initials: B
authors.lastname: Therrien
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D003517:Cyclopentanes / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007495:Iridium / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D012238:Rhodium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D003517:Cyclopentanes; D007495:Iridium; D012238:Rhodium; D005978:Glutathione