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Computer-assisted study on the reaction between pyruvate and ylide in the pathway leading to lactyl–ThDP

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Abstract

In this study the formation of the lactyl–thiamin diphosphate intermediate (L–ThDP) is addressed using density functional theory calculations at X3LYP/6-31++G(d,p) level of theory. The study includes potential energy surface scans, transition state search, and intrinsic reaction coordinate calculations. Reactivity is analyzed in terms of Fukui functions. The results allow to conclude that the reaction leading to the formation of L–ThDP occurs via a concerted mechanism, and during the nucleophilic attack on the pyruvate molecule, the ylide is in its AP form. The calculated activation barrier for the reaction is 19.2 kcal/mol, in agreement with the experimental reported value.

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Acknowledgments

The authors gratefully acknowledge financial support from Fondecyt, Grant No. 1100064.

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Authors and Affiliations

  1. Computational Biological Chemistry Group (QBC), Faculty of Chemical Sciences, Universidad de Concepción, Concepción, Chile

    Omar Alvarado, Gonzalo Jaña & Eduardo J. Delgado

  2. Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Sede Concepción, Universidad Andrés Bello, Concepción, Chile

    Gonzalo Jaña

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  1. Omar Alvarado
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  2. Gonzalo Jaña
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  3. Eduardo J. Delgado
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Correspondence to Eduardo J. Delgado.

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Alvarado, O., Jaña, G. & Delgado, E.J. Computer-assisted study on the reaction between pyruvate and ylide in the pathway leading to lactyl–ThDP. J Comput Aided Mol Des 26, 977–982 (2012). https://doi.org/10.1007/s10822-012-9589-3

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  • DOI: https://doi.org/10.1007/s10822-012-9589-3

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