VARIATION OF ACIDITY CONSTANTS OF PEPTIDES IN ACETONITRILE-WATER MIXTURES WITH SOLVENT COMPOSITION - EFFECT OF PREFERENTIAL SOLVATION

The dissociation constant values of a series of peptides in 5.54, 10, 16.30, 25.03 and 50% (w/w) acetonitrile-water mixed solvents at 298.15 K were determined according to the criteria endorsed by IUPAC. A pron ounced change in the acid-base pK values of carboxylic, phenol and thi ol groups was observed as the solvent was enriched in acetonitrile. By contrast, pK values of protonated amino-terminal groups were influenc ed slightly as the solvent was enriched in acetonitrile, although cont inually increasing pK values were observed. The variation of the pK va lues obtained, over the whole composition range studied, was explained by taking into account the preferential solvation of electrolytes in acetonitrile-water mixtures. To obtain pK values in all possible binar y solvent acetonitrile-water mixtures, relationships between pK values and different bulk properties were examined and the Linear Solvation Energy Relationships methodology was applied. The pK, values were then correlated with the Kamlet-Taft, pi, alpha and beta solvatochromic pa rameters of acetonitrile-water mixtures. The equations obtained allowe d calculation of the pK values of peptides in acetonitrile-water mixtu res up to 50% (w/w) and thus permitted the acid-base behavior of these substances in the widely used acetonitrile-water media to be known. ( C) Munksgaard 1997.