Density functional theory study of the thiolysis reaction in penicillins

Show simple item record Garcias, Rafael C. Coll, Miguel Donoso Pardo, Josefa Laurentina Muñoz Izquierdo, Francisco 2018-10-26T13:11:14Z
dc.description.abstract [eng] 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+G* level. The crucial role of the intramolecular bond in the beta-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 b 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 <br> 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 · 10-1 mol-1 dm3 s-1], which is roughly two orders of magnitude higher than for other thiols of similar basic strength.
dc.format application/pdf
dc.relation.isformatof Versió postprint del document publicat a:
dc.relation.ispartof Journal of Molecular Structure-Theochem, 2006, vol. 773, p. 29-34
dc.subject.classification 54 - Química
dc.subject.other 54 - Chemistry. Crystallography. Mineralogy
dc.title Density functional theory study of the thiolysis reaction in penicillins
dc.type info:eu-repo/semantics/article
dc.type info:eu-repo/semantics/acceptedVersion 2018-10-26T13:11:14Z info:eu-repo/date/embargoEnd/2075-01-01
dc.embargo 2075-01-01
dc.rights.accessRights info:eu-repo/semantics/embargoedAccess

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