Deuterium Isotope Effects on Acid-Base Equilibrium of Organic Compounds

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 ΔpKa=pKaD2O−pKaH2O versus pKaH2O, 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 ΔpKa change from Model 1 was found to be in reasonable agreement with the experimental average result, the pKaH2O 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.

Symmetry of Hydrogen Bonds: Application of NMR Method of Isotopic Perturbation and Relevance of Solvatomers

“…This arbitrariness merely leads to a halving of the effect possible from double labeling at one carboxyl). The equilibrium constant between the two tautomers, K T , or the ratio of 16 O and 18 O acidity constants, is >1, owing to differences in zero-point energies [34][35][36][37]. The 18 O-protonated tautomer is favored and thus weighted more heavily in the averaging.…”