Acid-base behaviour of tripeptides in solvents used in liquid chromatography. Correlation between pK values and solvatochromic parameters of acetonitrile-water mixtures

The dissociation constant values of a series of tripeptides 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 pronounced change in the acid-base pK values of carboxylic and phenolic groups was observed as the solvent was enriched in acetonitrile. Dissociation constant values of protonated terminal amino groups are slightly influenced by the addition of acetonitrile. The variation of pK values was explained by taking into account the preferential solvation of electrolytes in acetonitrile-water mixtures and electrostatic effects. Correlations of pK values and different bulk and microscopic properties of the solvents were examined and the Linear Solvation Energy Relationships (LSER) methodology was applied. The equation obtained permits calculation of pK values of the tripeptides in any acetonitrile-water mixture up to 50% (w/w) and can help to clarify the acid-base behaviour of tripeptides in the widely used acetonitrile-water mixed solvents.