DETERMINING 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 from the aqueous to a chiral micellar phase was measured for 12 pair s of enantiomeric pharmaceutical compounds, including beta-agonists, b eta-blockers, and other beta-amino alcohols. Selectivities, distributi on coefficients, and Gibbs free energies were also determined. Whereas the transfer of solute from aqueous phase to the chiral micellar phas e was always favorable from an enthalpic viewpoint (-19 < Delta H degr ees < -4 kJ/mol), it was not always so from an entropic perspective (- 12.1. < Delta S degrees < 56.9 J mol(-1) K-1). Dramatic differences in Delta H degrees and -->Delta S degrees were often observed between en antiomers. The enthalpy and entropy changes for the solutes follow a l inear free-energy relationship, indicating a similar enantiomeric mech anism of separation. Relationships between analyte structure and therm odynamic parameters were investigated to better understand the interac tions of enantiomers with N-dodecoxycarbonylvaline micelles. (C) 1996 John Wiley & Sons, Inc.