Mechanistic studies of La3+- and Zn2+-catalyzed methanolysis of aryl phosphate and phosphorothioate triesters. Development of artificial phosphotriesterase systems.
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 degrees C. Brønsted plots of the logk2 values vs. pKa for the phenol leaving groups give beta(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.
Liu
Tony
T
Department of Chemistry, Queen's University, Kingston, Ontario, Canada.
Neverov
Alexei A
AA
Tsang
Josephine S W
JS
Brown
R Stan
RS
D002384:Catalysis; D002412:Cations / Q000737:chemistry; D004951:Esterification; D007811:Lanthanum / Q000737:chemistry*; D000432:Methanol / Q000737:chemistry*; D015394:Molecular Structure; D010755:Organophosphates / Q000737:chemistry*; D009946:Organothiophosphorus Compounds / Q000737:chemistry*; D044345:Phosphoric Triester Hydrolases / Q000378:metabolism*; D015032:Zinc / Q000737:chemistry*
D002412:Cations; D010755:Organophosphates; D009946:Organothiophosphorus Compounds; D007811:Lanthanum; D044345:Phosphoric Triester Hydrolases; D015032:Zinc; D000432:Methanol