De terminati on of Acidic Dissociation Constants of ۵´-IMPand ۵´-UMP in Water using DFT Methods

Deriv atives of orthophosphoric acid, main ly as esters and anhydri des, are wid ely distributed in living systems. Th ey are part of the so-called phosph ate-sugar backbone of D NA and RN A; in the f orm of nucleotides th ey occur as coenzym es and intermediates [۱]. Inosine-۵'-mono phosphate ( IMP) is a nucleotide i mportant mo nophosphate in metabo lism. Uridine-۵'-mono phosphate ( UMP) is a nucleotide th at is used as a monom er in RNA. It is formed from Orotid ine-۵'-mon phosphate in a dec arboxylation reaction catalyzed by the enzyme orotidylate decarb oxylase [۲]. The acid-base behavio r of nucleot ides, nucleo sides, base s, and polyn ucleotides is essential to deduce the speciation and the possible conformational changes with p H in soluti on [۳]. On the other han d, during t he last two decades ther e has been much intere st in develop ing a metho dology ena bling theoretical prediction of pKa v alues, employing variou s quantum theoretical techniques. Kinds of polarizable continuum m odels have been applied to calculate free energy differenc es for cations, neutral compounds and their a nions. On the basis of solvation fre e energies, the pKa values were obtained for the compoun ds in question by using thermody namic equations; invo lving the combined e xperimental and calculated data [۴]. This paper deals with the influence of fact ors such as the SCRF model applied, choice of a particula r thermodynmic equations, atomic radii used to build a cavity in the solvent (water ), optimization of geom etry in water, inclusio n of electro n correlation , and the di mension of t he basis set on the solvation free en ergies and on the calculated pKa values. In this study, pKa values of IMP and UM P were determined in aqueous solution by ab initio method and tempe rature ۲۵°C.

کلیدواژه ها:

Dissociation constant ، IMP ، U MP ، DFT m ethod ، solvation free en ergy