A Synthetic Model for the Inhibition of Glutathione Peroxidase by Antiarthritic Gold Compounds

作者：Bhabak Krishna P; Mugesh Govindasamy^*

来源：Inorganic Chemistry, 2009, 48(6): 2449-2455.

DOI：10.1021/ic8019183

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-(NN-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 convened 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.

• 出版日期2009-3-16