Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5418229 | Journal of Molecular Structure: THEOCHEM | 2006 | 6 Pages |
Abstract
The chemical behaviour of the penicillin nucleus towards nucleophilic attack by two thiols of disparate basicity such as 2-mercaptoethanol (1) and 2-mercaptoethylamine (2) was studied using density functional theory computations at the B3LYP/6-31+Gâ level. The crucial role of the intramolecular bond in the β-lactam nitrogen was examined. Based on the energy values obtained, the formation of the tetrahedral intermediate (T in Scheme 1) is the rate-determining step of the process. The energies of activation for the process suggest general acid catalysis in 2 as a result of the presence of an effective proton donor group in β in the starting thiolate. This reduces the energy of formation of the tetrahedral intermediate from 12.04 kcal/mol for 1 to 4.51 kcal/mol for 2 - which possesses a more acidic group. This disparate behaviour is consistent with the experimental rate constant for the degradation of benzyl-penicillin in the presence of 2 [k1(2) = 1.3 Ã 10â1 molâ1 dm3 sâ1], which is roughly two orders of magnitude higher than for other thiols of similar basic strength.
Related Topics
Physical Sciences and Engineering
Chemistry
Physical and Theoretical Chemistry
Authors
Rafael C. GarcÃas, Miguel Coll, Josefa Donoso, Francisco Muñoz,