Thiol-catalysed hydrolysis of benzylpenicillin

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

Research output: Contribution to journalArticle

16 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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Penicillin G
Sulfhydryl Compounds
Hydrolysis
Anions
Alkalinity
Isotopes
Activation energy
Nuclear magnetic resonance
Catalysts
Kinetics
Acids
Water

Cite this

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
Llinás, Antonio ; Donoso, Josefa ; Vilanova, Bartolomé ; Frau, Juan ; Muñoz, Francisco ; Page, Michael I. / Thiol-catalysed hydrolysis of benzylpenicillin. In: Journal of the Chemical Society. Perkin Transactions 2. 2000 ; No. 7. pp. 1521-1525.
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Llinás, A, Donoso, J, Vilanova, B, Frau, J, Muñoz, F & Page, MI 2000, 'Thiol-catalysed hydrolysis of benzylpenicillin', Journal of the Chemical Society. Perkin Transactions 2, no. 7, pp. 1521-1525. https://doi.org/10.1039/B001091J

Thiol-catalysed hydrolysis of benzylpenicillin. / Llinás, Antonio; Donoso, Josefa; Vilanova, Bartolomé; Frau, Juan; Muñoz, Francisco; Page, Michael I.

In: Journal of the Chemical Society. Perkin Transactions 2, No. 7, 07.2000, p. 1521-1525.

Research output: Contribution to journalArticle

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