THEORETICAL STUDIES ON THE DECARBOXYLATION REACTION IN THIAMIN CATALYSIS

摘要

The conformational behavior and the stability of thiazolium and thiamin diphosphate (ThDP) adducts formed by the C2 addition of the substrates pyruvate and glyoxylate to the corresponding thiamin systems are investigated within the force-field version PIMM90 as well as the semiempirical AM1 and PM3 methods. Moreover, the reaction coordinate of the decarboxylation process of the adducts with respect to the C2 alpha-COO- bond are calculated by PM3 and AM1. The calculations on the key intermediates of the Breslow mechanism are performed in order to study the steric aspects of both substrate adducts that show a different pathway in the catalytic cycle. The alternative structural findings for the decarboxylation products are compared with first 6-31G* studies on the corresponding thiazolium model systems. Especially, the PM3 calculations show that the elimination of CO2 is favored if the arrangement of the carboxylate group is nearly perpendicular to the plane of the thiazolium ring. These results support the least-motion maximum-overlap mechanism in the enzymatic decarboxylation reaction, proposed by Kluger. The most stable conformers of the ThDP adducts and its decarboxylation products are characterized by V-like structures and the formation of a significant intramolecular hydrogen bonding under participation of the 4'-aminopyrimidine ring. (C) 1996 John Wiley & Sons, Inc. [References: 14]