Theoretical study of omeprazole behavior: Racemization barrier and decomposition reaction

Nenhuma Miniatura disponível

Data

2008-05-01

Orientador

Coorientador

Pós-graduação

Curso de graduação

Título da Revista

ISSN da Revista

Título de Volume

Editor

John Wiley & Sons Inc

Tipo

Artigo

Direito de acesso

Acesso restrito

Resumo

omeprazole is a substituted benzimidazole which suppresses gastric-acid secretion by means of H+, K+-ATPase inhibition. It is an optically active drug with the sulfur of the sulfoxide being the chiral center. This pro-drug can be easily converted into its respective sulfenamide at low pH. In this work, omeprazole has been studied in relation to racemization barrier and decomposition reaction. Quantum chemistry coupled to PCA chemometric method were used to find all minimum energy structures. Conformational analysis and calculation of racemization barriers were carried out by PM3 semiempirical method (Gaussian 98). The average racemization energy barrier for all minimum energy structures (43.56 kcal mol(-1)) can be related to the velocity constant in Eyring's equation. The enormous half-life time at 100 degrees C (9.04 x 10(4) years) indicates that the process cannot be observed in human time scale. on the other hand, the difference of free energy change (Delta(Delta G) = -266.78 kcal mol(-1)) for the decomposition reaction shows that the process is favorable to the sulfenamide formation. The highly negative Delta(Delta G) obtained for the decomposition reaction shows that this process is extremely exothermic. This result explains why omeprazole decomposes and does not racemize. (C) 2008 Wiley Periodicals, Inc.

Descrição

Idioma

Inglês

Como citar

International Journal of Quantum Chemistry. Hoboken: John Wiley & Sons Inc, v. 108, n. 6, p. 1097-1106, 2008.

Itens relacionados

Financiadores