title: A synthetic model for the inhibition of glutathione peroxidase by antiarthritic gold compounds.
abstract: In this paper, inhibition of the glutathione peroxidase activity of two synthetic organoselenium compounds, bis[2-(N,N-dimethylamino)benzyl]diselenide (5) and bis[2-(N,N-dimethylamino)benzyl]selenide (9), by gold(I) thioglucose (1), chloro(triethylphosphine)gold(I), chloro(trimethylphosphine)gold(I), and chloro(triphenylphosphine)gold(I) is described. The inhibition is found to be competitive with respect to a peroxide (H(2)O(2)) substrate and noncompetitive with respect to a thiol (PhSH) cosubstrate. The diselenide 5 reacts with PhSH to produce the corresponding selenol (6), which upon treatment with 1 equiv of gold(I) chlorides produces the corresponding gold selenolate complexes 11-13. However, the addition of 1 equiv of selenol 6 to complexes 11-13 leads to the formation of bis-selenolate complex 14 by ligand displacement reactions involving the elimination of phosphine ligands. The phosphine ligands eliminated from these reactions are further converted to the corresponding phosphine oxides (R(3)P=O) and selenides (R(3)P=Se). In addition to the replacement of the phosphine ligand by selenol 6, an interchange between two different phosphine ligands is also observed. For example, the reaction of complex 11 having a trimethylphosphine ligand with triphenylphosphine produces complex 13 by phosphine interchange reactions via the formation of intermediates 15 and 16. The reactivity of selenol 6 toward gold(I) phosphines is found to be similar to that of selenocysteine.
authors.affiliation: Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Krishna P
authors.initials: KP
authors.lastname: Bhabak
authors.forename: Govindasamy
authors.initials: G
authors.lastname: Mugesh
mesh_terms: D001168:Arthritis / Q000188:drug therapy*; D032701:Biomimetics; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017612:Gold Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008954:Models, Biological; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D017612:Gold Compounds; D016566:Organoselenium Compounds; D005979:Glutathione Peroxidase