Mechanistic studies of La3+- and Zn2+-catalyzed methanolysis of aryl phosphate and phosphorothioate triesters. Development of artificial phosphotriesterase systems

Abstract

The methanolyses of a series of O,O-diethyl O-aryl phosphates (2,5) and O,O-diethyl S-aryl phosphorothioates (6) promoted by methoxide and two metal ion systems, (La³⁺)₂(⁻OCH₃)₂ and 4:Zn²⁺:⁻OCH₃ (4 = 1,5,9-triazacyclododecane) has been studied in methanol at 25 °C. Brønsted plots of the logk₂ values vs.^s_spK_a for the phenol leaving groups give β_lg values of −0.70, −1.43 and −1.12 for the methanolysis of the phosphates and −0.63, −0.87 and −0.74 for the methanolysis of the phosphorothioates promoted by the methoxide, La³⁺ and Zn²⁺ systems respectively. The kinetic data for the metal-catalyzed reactions are analyzed in terms of a common mechanism where there is extensive cleavage of the P–XAr bond in the rate-limiting transition state. The relevance of these findings to the mechanism of action of the phosphotriesterase enzyme is discussed.