Abstract
Deuterium isotope effects on acid–base equilibrium have been investigated using a combined path integral and free-energy perturbation simulation method. To understand the origin of the linear free-energy relationship of versus , we examined two theoretical models for computing the deuterium isotope effects. In Model 1, only the intrinsic isotope exchange effect of the acid itself in water was included by replacing the titratable protons with deuterons. Here, the dominant contribution is due to the difference in zero-point energy between the two isotopologues. In Model 2, the medium isotope effects are considered, in which the free energy change as a result of replacing H2O by D2O in solute–solvent hydrogen-bonding complexes is determined. Although the average change from Model 1 was found to be in reasonable agreement with the experimental average result, the dependence of the solvent isotope effects is absent. A linear free-energy relationship is obtained by including the medium effect in Model 2, and the main factor is due to solvent isotope effects in the anion–water complexes. The present study highlights the significant roles of both the intrinsic isotope exchange effect and the medium solvent isotope effect.
Highlights
The free energy difference between different isotopologues in Equations (6b) and (7b) defined in each pair of square brackets is related to the ratio of the quantum mechanical partition functions of two isotopic isomers, which can be directly obtained from path integral-free energy perturbation (PI-FEP) theory in molecular dynamics simulations in an explicit solvent [34]
It is significant that the present study unequivocally showed that the trend of pKaH2 O dependence of the solvent isotope effects on the acid–base equilibrium constant is due to the medium effect, originating from the isotope effects in the specific hydrogen bonding interactions of the acid and its conjugated base to donate and to accept a hydrogen bond from the solvent H2O or D2O
Deuterium isotope effects on the acid–base equilibrium of a series of organic acids consisting of alcohols, phenol derivatives, and carboxylic acids have been determined using a mixed path integral and free-energy perturbation simulation method
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Two important factors have been proposed to contribute to the observed acidity change of organic acids, including (1) the difference in zero-point energy of the acids in water and in heavy water and (2) isotope effects on intermolecular interactions between solute and solvent molecules [3,4,15,16,17] The former is due to the isotope exchange effect of the acid, corresponding to the replacement of a protium (considering only one titratable site) of the acid by a deuterium, whereas the latter is a medium effect as a result of the removal of the solute (acid and its conjugate base) from water into heavy water [3,4]. We present and discuss the computational results along with a summary of the mai
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