Chemical reaction mechanisms in solution from brute force computational Arrhenius plots
2015 (English)In: Nature Communications, ISSN 2041-1723, Vol. 6, 7293Article in journal (Refereed) Published
Decomposition of activation free energies of chemical reactions, into enthalpic and entropic components, can provide invaluable signatures of mechanistic pathways both in solution and in enzymes. Owing to the large number of degrees of freedom involved in such wcondensed-phase reactions, the extensive configurational sampling needed for reliable entropy estimates is still beyond the scope of quantum chemical calculations. Here we show, for the hydrolytic deamination of cytidine and dihydrocytidine in water, how direct computer simulations of the temperature dependence of free energy profiles can be used to extract very accurate thermodynamic activation parameters. The simulations are based on empirical valence bond models, and we demonstrate that the energetics obtained is insensitive to whether these are calibrated by quantum mechanical calculations or experimental data. The thermodynamic activation parameters are in remarkable agreement with experiment results and allow discrimination among alternative mechanisms, as well as rationalization of their different activation enthalpies and entropies.
Place, publisher, year, edition, pages
2015. Vol. 6, 7293
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
IdentifiersURN: urn:nbn:se:uu:diva-259120DOI: 10.1038/ncomms8293ISI: 000357171100007PubMedID: 26028237OAI: oai:DiVA.org:uu-259120DiVA: diva2:843290
FunderSwedish Research CouncilKnut and Alice Wallenberg Foundation