Computing pK_a Values in Different Solvents by Electrostatic Transformation

Abstract

We introduce a method that requires only moderate computational effort to compute pKa values of small molecules in different solvents with an average accuracy of better than 0.7 pH units. With a known pKa value in one solvent, the electrostatic transform method computes the pKa value in any other solvent if the proton solvation energy is known in both considered solvents. To apply the electrostatic transform method to a molecule, the electrostatic solvation energies of the protonated and deprotonated molecular species are computed in the two considered solvents using a dielectric continuum to describe the solvent. This is demonstrated for 30 molecules belonging to 10 different molecular families by considering 77 measured pKa values in 4 different solvents: water, acetonitrile, dimethyl sulfoxide, and methanol. The electrostatic transform method can be applied to any other solvent if the proton solvation energy is known. It is exclusively based on physicochemical principles, not using any empirical fetch factors or explicit solvent molecules, to obtain agreement with measured pKa values and is therefore ready to be generalized to other solute molecules and solvents. From the computed pKa values, we obtained relative proton solvation energies, which agree very well with the proton solvation energies computed recently by ab initio methods, and used these energies in the present study.

Absolute proton hydration free energy, surface potential of water, and redox potential of the hydrogen electrode from first principles: QM/MM MD free-energy simulations of sodium and potassium hydration

“…Clearly, the formulation of a consistent single-ion solvation thermodynamics also involves analogous determinations pertaining to other solvents, 151,322 relevant in particular in the context of transfer free energies, 323,324 and charge-asymmetric solvation effects. 17,325 Furthermore, not only the values of these quantities are of relevance, but also that of their P-or/and T -derivatives, related to the partial molar enthalpies, entropies, compressibilities, and expansivities.…”

Molecular acidity: An accurate description with information‐theoretic approach in density functional reactivity theory

“…Essential in many chemical and biological phenomena and processes, molecular acidity, the ability for a Brønsted–Lowry acid to lose a proton, is one of the fundamental, intrinsic, and most important physiochemical properties of a molecular system. Yet, its accurate prediction is still an unaccomplished task in the literature . Molecular acidity can be represented by the p K a value as the measure of its acidity strength.…”

“…Yet, its accurate prediction is still an unaccomplished task in the literature. [1][2][3][4][5][6][7][8][9][10][11][12] Molecular acidity can be represented by the pK a value as the measure of its acidity strength. In principle, the pK a value of an acid, HA, is defined as the negative logarithm, pK a 5 2log 10 K a , of the equilibrium constant K a of the acid dissociation reaction, HA 5 A -1 H 1 , with K a 5 [A -][H 1 ]/ [HA].…”

Large‐Sized Ammonia Clusters and Solvation Energies of the Proton in Ammonia

“…Several investigations have been performed to determine the solvation energies of the proton in water . Besides, only few authors have been interested in the solvation energies of the proton in other solvents such as methanol, acetonitrile, dimethyl sulfoxide, acetone, benzene, ethanol, and ammonia .…”

“…Several investigations have been performed to determine the solvation energies of the proton in water. [5][6][7][8][9][10][11][12][13][14][15] Besides, only few authors have been interested in the solvation energies of the proton in other solvents such as methanol, acetonitrile, dimethyl sulfoxide, acetone, benzene, ethanol, and ammonia. [4,[16][17][18][19][20][21][22][23] Recently, we reported the solvation free energy and the solvation enthalpy of the proton in ammonia and in methanol at a wide range of temperatures.…”