Determination of Acidic Dissociation Constants of Glycine, Valine, Phenylalanine, Glycylvaline, and Glycylphenylalanine in Water Using ab Initio Methods

Abstract

In this study, pKa values of glycine, valine, phenylalanine, glycylvaline, and glycylphenylalanine were determined in aqueous solution by an ab initio method. To explain the acidic dissociation constants obtained, we investigated the molecular conformations and solute−solvent interactions of the peptides and amino acid anions, using the density functional theory (DFT) method. Several ionization reactions and equilibria in protic solvents, which possess a high hydrogen-band-donor capability, are shown. The mentioned reactions and equilibria constitute the indispensable theoretical basis to calculate the acidity constants of glycine, valine, phenylalanine, glycylvaline, and glycylphenylalanine. Basis sets at the B3LYP/6-31+G(d) level of theory were used for calculations. Tomasi’s method was used to analyze the formation of intermolecular hydrogen bonds between the existent species and water molecules. In this way, it was determined that in alkaline aqueous solutions the cation, anion, and neutral species of glycine, valine, phenylalanine, glycylvaline, and glycylphenylalanine are solvated with one, two, three, and four molecules of water, respectively. In this study, there is comparable agreement between the experimentally determined pKa values for the acid−base reactions selected by potentiometric and those reported in the literature demonstrating the theoretically calculated pKa values.