CAPILLARY ELECTROPHORESIS WITH CHIRAL SELECTORS - OPTIMIZATION OF SEPARATION AND DETERMINATION OF THERMODYNAMIC PARAMETERS FOR BINDING OF TIOCONAZOLE ENANTIOMERS TO CYCLODEXTRINS

A systematic approach is outlined for optimization of enantiomeric sep arations in free solution capillary electrophoresis using chiral mobil e-phase additives. Maximum electrophoretic mobility difference between the enantiomers occurs when the concentration of free selector is equ al to the reciprocal of the average binding constant. General equation s and data analysis methods are presented to relate mobilities to equi librium constants in simple and competitive binding equilibria and use d to determine thermodynamic parameters for host-guest complexation of tioconazole enantiomers with a range of cyclodextrin selectors. Selec tivities are found to be in the reverse order of binding constants in the series dimethyl-beta-cyclodextrin (K-1 = 6.9 X 10(3) M(-1), alpha = 1.10) to hydroxypropyl-beta-cyclodextrin (K-1 = 0.72 x 10(3) M(-1), alpha = 1.29). For beta-cyclodextrin (K-1 = 1.32 x 10(3) M(-1), alpha = 1.20), Delta H degrees provides the dominant contribution to binding but Delta Delta H degrees and T Delta Delta S degrees terms give comp arable contributions to the selectivity. Addition of alcohol does not affect the selectivity, but allows displacement of the optimum separat ion conditions to higher cyclodextrin concentration through either com petitive binding (with cyclohexanol) or preferential solvation of reac tants (with methanol).