A computational study of the intramolecular deprotonation of a carbon acid in aqueous solution

Raman Sharma, Michelle Thorley, Jonathan P. McNamara, C. Ian F Watt, Neil A. Burton

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Proton transfer reactions are the rate-limiting steps in many biological and synthetic chemical processes, often requiring complex cofactors or catalysts to overcome the generally unfavourable thermodynamic process of carbanion intermediate formation. It has been suggested that quantum tunnelling processes enhance the kinetics of some of these reactions, which when coupled to protein motions may be an important consideration for enzyme catalysis. To obtain a better fundamental and quantitative understanding of these proton transfer mechanisms, a computational analysis of the intramolecular proton transfer from a carbon acid in the small molecule, 4-nitropentanoic acid, in aqueous solution is presented. Potential-energy surfaces from gas-phase, implicit and QM/MM (quantum mechanical/molecular mechanical) explicit solvation quantum chemistry models are compared, and the potential of mean force, for the full reaction coordinate, using umbrella-sampling molecular dynamics is analysed. Semi-classical multidimensional tunnelling corrections are also used to estimate the quantum tunnelling contributions and to understand the origin of the primary deuterium kinetic isotope effects (KIEs). The computational results are found to be in excellent agreement with the KIEs and the energetics obtained experimentally. © the Owner Societies.
    Original languageEnglish
    Pages (from-to)2475-2487
    Number of pages12
    JournalPhysical Chemistry Chemical Physics
    Volume10
    Issue number18
    DOIs
    Publication statusPublished - 2008

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