Thiol-catalysed hydrolysis of benzylpenicillin
Llinás, Antonio; Donoso, Josefa; Vilanova, Bartolomé; Frau, Juan; Muñoz, Francisco; Page, Michael I.; Llinás Antonio; Department of Chemical and Biological Sciences, The University of Huddersfield; Donoso Josefa; Departament de QuÃmica, Facultat de Ciències, Universitat de les Illes Balears; Vilanova Bartolomé; Departament de QuÃmica, Facultat de Ciències, Universitat de les Illes Balears; Frau Juan; Departament de QuÃmica, Facultat de Ciències, Universitat de les Illes Balears; Muñoz Francisco; Departament de QuÃmica, Facultat de Ciències, Universitat de les Illes Balears; Page Michael I.; Department of Chemical and Biological Sciences, The University of Huddersfield
Журнал:
Journal of the Chemical Society, Perkin Transactions 2
Дата:
2000
Аннотация:
Thiolysis of benzylpenicillin has been investigated by HPLC and <sup>1</sup>H-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 2.2â 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<sup>â 1</sup>.1 kcalâ =â 4.184 kJ.
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