First Principle Studies of Acidities of Some Amino Acids and Dipeptides

In some industries such as food and chemicals, accurate prediction of acidity constants isvitally important. Many compounds that are used as drugs are weak acids or bases. Enzymekinetic in living organisms depends on the acidity constants of compounds present in the cell.For synthesis of transition metal complexes with special characteristics, the acidity constants ofligands need to be determined. At a glance, prediction of acidity constants is very important inchemistry, biochemistry, medicine, and so on [1,2]. The pKa values are usually measured throughexperimental methods such as voltammetry, spectroscopy, potentiometry, conductometry,capillary electrophoresis and competitive reactions [3]. However, experimental measurements ofpKa values of various compounds are still estimated. Also, these measurements are not easy orpractical for all compounds. As a result, nowadays there is a great interest in using computationalmethods to determine the acidity or basicity constants of a big number of different moleculessuch as amino acids that are part of a larger polypeptide chain. Among the computationalmethods for determining acidity constants, using thermodynamic cycles is more common. In theprevious works, some of us calculated pKa values of some drug using computational approaches[4-5]. In the present work, pKa values of some amino acids and its corresponding dipeptides werecalculated through direct thermodynamic cycle. For this aim, various DFT functionals, levels oftheory, cavity models, and solvation models were applied to find the best method. The obtainedresults were consistent with the available pKa values for the studied compounds. It can beconcluded that pKa determination approaches based on thermodynamic cycle can be reliable andaccurate if the suitable computational methods be selected.

Keywords:

pKa , Amino acids , Dipeptides , Computational Methods , Solvation Models