CALCULATION OF ABSOLUTE AND RELATIVE ACIDITIES OF SUBSTITUTED IMIDAZOLES IN AQUEOUS SOLVENT

We calculate free energy changes of ionization reactions in aqueous so lvent using a self-consistent reaction field method. In the calculatio ns all species are treated as quantum mechanical solutes coupled to a solvent dielectric continuum. We show for a series of substituted imid azole compounds that both absolute and relative pK(a) values for the d eprotonation of nitrogen on the imidazole ring can be obtained with an average absolute deviation of 0.8 units from experiment. This degree of accuracy is possible only if the solutes are treated at the correla ted level using either G2 type or density functional theory. Inconsist encies in published experimental free energies of hydration that might undermine the reliability of the calculated absolute pK(a) values are discussed.