New Density Functional and Atoms in Molecules Method of Computing Relative pK_aValues in Solution

Abstract

A theoretical structure−property relation between pK a and Bader's atoms in molecules (AIM) energy of the dissociating proton was obtained by an approximation of the standard gas-phase expression for the equilibrium constant expressed in terms of molecular partition functions. This relation was then tested by solvated density functional computations on a series of aliphatic carboxylic acids, substituted benzoic acids, phenols, anilinium ions, and pyridinium ions using the COSMO solvation model. Comparison with accurate experimental values indicates that average unsigned errors of generally less than 0.2 pK a units can be achieved in the calculation of relative pK a values. The inclusion of specifically hydrogen-bonded water molecules in the vicinity of the dissociating proton was found to improve the agreement between theory and experiment greatly. Computed pK a values for some diprotic acids were also investigated.

Density functional theoretical study of pKa of RCOOH (RH, CH3, and C2H5) using the combination of the extended clusters‐continuum model

“…All the calculated pK a values at HF/6-311þþg(d,p) levels lead to very large error compared with the experimental data. Although Adam [17] thinks that carboxylic acid requires two water molecules to make an accurate pK a prediction, we suggest that an accurate pK a prediction requires three water molecules, which can be verified by Table III. To analyze the structure of the clusters (of Fig.…”

Theoretical calculations of the relative pKa values of some selected aromatic arsonic acids in water using density functional theory

“…Accordingly, many researchers are tending to calculation of pKa values using theoretical and computational approaches. 21,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] Recently quantum chemical calculations, using thermodynamical parameters such as Gibbs free energy, have reported good correlations between calculated and experimental acidities of a wide range of organic and inorganic acids. 18,[42][43][44][45][46][47][48][49][50] For example, gas phase and solution phase acidities of some organic compounds investigated by Namazian et al and Kheirjou et al reported good correlation between ab initio calculations of pKa values with the experimental data.…”

Improving the study of proton transfers between amino acid side chains in solution: choosing appropriate DFT functionals and avoiding hidden pitfalls

“…A good theoretical description of these reaction mechanisms therefore depends on the ability to predict accurately the solution pK a of the reacting functional groups. Several protocols for computational determination of pK a have been developed by several authors [1][2][3][4][5][6]. They all rely on the determination of gas-phase reaction energies, followed by computation of solvation energies of the basic and acidic forms of the molecular species under study using implicit solvent models [1][2][3]5,6] or the Poisson equation [4], in the presence [2,3,5,6] or absence [1,4,6] of a few explicit water molecules.…”