A preferential solvation model that relates solute properties with solvent
composition in binary mixtures has been applied to the dissociation pK(a) v
alues of a set of 28 substituted phenols in methanol-water mixtures. The pa
rameters of the model allow estimation of the pK(a) value of each phenol fo
r any methanol-water composition. Moreover, it is demonstrated that the pK(
a) values of the whole set of phenols at any methanol-water composition are
linearly related to the pK(a) values of the phenols in water. Equations th
at relate the correlations' slope and intercept values with the solvent com
position have been derived and tested with the set of phenols. The general
parameters obtained for these equations allow an accurate calculation of th
e pK(a) value of any phenol, even of those not included in the original set
, at any methanol-water composition solely from the pK(a) value of the phen
ol in water. These calculated pK(a) values can be used for quantitative str
ucture-HPLC retention relationships. The method is tested by comparison of
the calculated pK(a) values with the HPLC determined pK(a) values of 26 phe
nols in a polymeric column with a 50% methanol as mobile phase. (C) 2000 El
sevier Science B.V. All rights reserved.