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

Abstract

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.