Determination of acidic dissociation constants of glutamine and isoleucine in water using ab initio methods

Objective: In this study, pKa values of glutamine and isoleucine were determined in aqueous solution by ab initio and DFT methods. To explain the obtained values of pKa, the molecular conformations and solute-solvent interactions of the anions, cations, and neutrals molecules of glutamine and isoleucine were investigated. The experimental determination of these values, apart from been laborious, is a challenge because of the low water solubility of these compounds. Methods: We have evaluated different models to determination of pKa, using the density functional theory (DFT) method at the B3LYP level of the theory. Results: this study shows the several ionization reactions and equilibriums in protic solvent, which possess a high hydrogen-band-donor capability. These reactions and equilibriums constitute the indispensable theoretical basis for calculation of glutamine and isoleucine acidity constants. Tomasi’s method was used to analyze the formation of intermolecular hydrogen bonds between the existent species and water molecules. In this way, it is proposed that in alkaline aqueous solutions the cation, anion, and neutral species of glutamine and isoleucine are solvated with one, two, three, and four molecules of water, respectively. In this study, there is comparable agreement between the experimental and calculated pKa values for the acid-base reactions proposed. Conclusion: In this paper, The calculations performed at the B3LYP/6-31+G(d) levels of theory using Tomasi’s method allowed us to prove that cations, neutral molecules, and anions form IHBs with some molecules of water. It is shown that, theoretically calculated pKa values are in good agreement with the existing experimental pKa values, which are determined from potentiometric titration and UV–visible spectrophotometric measurements.