Theoretical Chemistry Accounts

, 135:251 | Cite as

Theoretical determination of aqueous acid–base pK values: electronic structure calculations and steered molecular dynamic simulations

  • S. TolosaEmail author
  • J. A. Sansón
  • A. Hidalgo
  • N. Mora-DiezEmail author
Regular Article


The equilibrium constant (K) of several acid–base equilibria involving isomers of acetohydroxamic acid in aqueous solution is studied from a theoretical point of view applying electronic structure methods (at the M06-2X-SMD/6-311++G(d,p) and MP2-PCM/6-311++G(d,p) levels of theory) and steered molecular dynamic (SMD) simulations. The similarity of the results obtained indicates that SMD simulations can be successfully used to evaluate Gibbs energy changes in acid–base reactions in solution and pK values since these properties are in agreement with those found with quantum calculation and thermodynamic cycles. In the process of proton transfer from the imide isomers (the ZI and EI structures) toward the anion Z-amide, the deprotonation of the ZI(COH) molecule is the most favorable process kinetically and thermodynamically. It is observed that pK values are slightly higher for E-isomers and, particularly, for the deprotonation from the oxime group EI(NOH). Finally, we must emphasize the goodness of SMD simulations in solution to calculate this property as an alternative to using continuum solvation methods.


Aqueous pK calculations Acid–base equilibria SMD simulations M06-2X MP2 



This research was sponsored by the Consejería de Infraestructuras y Desarrollo Tecnológico de la Junta de Extremadura (Project GR15003) and the Natural Sciences and Engineering Research Council of Canada (NSERC).

Supplementary material

214_2016_2008_MOESM1_ESM.docx (32 kb)
Tables S1 and S2 collects the thermodynamic data. Table S3 presents the Cartesian coordinates for each molecule calculate at M06-2X-SMD and MP2-PCM levels, and Table S3 shows the Cartesian coordinates of transition state and product systems from SMD simulations (DOCX 32 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Departamento de Ingeniería Química y Química FísicaUniversidad de ExtremaduraBadajozSpain
  2. 2.Department of ChemistryThompson Rivers UniversityKamloopsCanada

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