Thiol-catalysed hydrolysis of benzylpenicillin

Antonio Llinás, Josefa Donoso, Bartolomé Vilanova, Juan Frau, Francisco Muñoz, Michael I. Page

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17 Citations (Scopus)

Abstract

Thiolysis of benzylpenicillin has been investigated by HPLC and 1H-NMR techniques. Thiols catalyse the hydrolysis of benzylpenicillin through the formation of a thioester intermediate. The catalytically reactive form of the thiol has been demonstrated to be the thiolate anion. Variation of reactivity with changing basicity of the thiolate anion generates a Brønsted βnuc value of 0.96, indicating that the breakdown of the tetrahedral intermediate is the rate-limiting step, as occurs in aminolysis and alcoholysis. Solvent kinetic isotope effects of 2.2-2.4 indicate that the solvent, water, probably acts as a general acid catalyst in the breakdown of the tetrahedral intermediate. PM3 theoretical calculations support the proposal that breakdown of the tetrahedral intermediate is rate-limiting. The experimental activation energies for the thiolysis of benzylpenicillin vary from 6.9 to 10.4 kcal mol-1.

Original languageEnglish
Pages (from-to)1521-1525
Number of pages5
JournalJournal of the Chemical Society. Perkin Transactions 2
Issue number7
Early online date24 May 2000
DOIs
Publication statusPublished - Jul 2000

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    Llinás, A., Donoso, J., Vilanova, B., Frau, J., Muñoz, F., & Page, M. I. (2000). Thiol-catalysed hydrolysis of benzylpenicillin. Journal of the Chemical Society. Perkin Transactions 2, (7), 1521-1525. https://doi.org/10.1039/B001091J