Transition State of the Base-Promoted Ring-Opening of Isoxazoles. Theoretical Prediction of Catalytic Functionalities and Design of Haptens for Antibody Production

Autor:	K. N. Houk, Donald Hilvert, Jim Na
Rok vydání:	1996
Předmět:	Formic acid General Chemistry Activation energy Biochemistry Catalysis Reaction rate chemistry.chemical_compound Colloid and Surface Chemistry chemistry Computational chemistry Organic chemistry Formate Carboxylate Methanol Isoxazole
Zdroj:	Journal of the American Chemical Society. 118:6462-6471
ISSN:	1520-5126 0002-7863
Popis:	In previous research, Hilvert and co-workers developed an antibody which catalyzes the decomposition of a nitrobenzisoxazole with a rate >108 times faster than the acetate-catalyzed reaction in water. Quantum mechanical calculations were carried out on a model system, the reaction of isoxazole with formate. The orientation of the carboxylate group has a significant effect on the rate. Complexation of the formate base by one water retards the reaction by approximately 5 kcal/mol; hence desolvation of the catalytic base could account for as much as four orders of magnitude in reaction rate. It was also determined that hydrogen-bonding to the forming oxide could potentially lead to greater rate acceleration. The gas phase activation barriers predict that water is the most effective general acid, lowering the activation energy by 9.5 kcal/mol. Methanol and formic acid are also effective, lowering the activation energy by 7.5 and 7.8 kcal/mol, respectively. Our calculations suggest that the combined effects of...
Databáze:	OpenAIRE
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