INFLUENCE OF INORGANIC COUNTERION ON THERMODYNAMIC QUANTITIES OF MICELLAR SOLUBILIZATION OF CHIRAL PHARMACEUTICAL COMPOUNDS IN AQUEOUS-SOLUTIONS OF N-DODECOXYCARBONYLVALINE USING MICELLAR ELECTROKINETIC CHROMATOGRAPHY

Using the van't Hoff relationship, the enthalpy and entropy of transfe r of 12 pairs of enantiomeric pharmaceutical compounds, including beta -agonists, beta-blockers, and other beta-amino alcohols, were measured from the aqueous phase to three different counterion (Li+, Na+, and K +) chiral micellar phases. Selectivities, distribution coefficients, a nd Gibbs free energies were also determined. Whereas the transfer of s olute from the aqueous phase to the chiral micellar phase was nearly a lways favorable from an enthalpic viewpoint (-23 < Delta H degrees < 1 kJ/mol), it was not always so from an entropic perspective (-25 < Del ta S degrees < 57 J/mol K). Dramatic differences in Delta H degrees an d Delta S degrees were often observed between enantiomers. The lithium counterion system gave the most favorable entropic contribution (posi tive Delta S) to the free energy of solute transfer, while the potassi um counterion system gave the most favorable enthalpic contribution (n egative Delta H degrees). The enthalpy and entropy changes for the sol utes follow a linear free-energy relationship for all counterion syste ms, indicating a similar enantiomeric mechanism of separation. Experim entally determined thermodynamic parameters were related to changes in the polarity of the N-dodecoxycarbonylvaline micelles as a function o f counterion to better understand the interactions of enantiomers with these micelles. In contrast to the large changes in Delta H degrees a nd Delta S degrees observed for individual solutes as the counterion w as changed, Delta G degrees and enantioselectivity remained similar, ( C) 1998 John Wiley & Sons, Inc.