Structural and temperature effects on enantiomer separations of bicyclo[2.2.2]octane-based 3-amino-2-carboxylic acids on cinchona alkaloid-based zwitterionic chiral stationary phases

Abstract

Procedures for the direct high-performance liquid chromatographic enantiomer separation of four bicyclo[2.2.2]octane-based 3-amino-2-carboxylic acids were developed in polar-ionic mode on zwitterionic chiral stationary phases (CSPs) based on cinchonane alkaloide quinine, quinidine and chiral sulfonic acid motifs. The effects of the mobile phase composition including the type of acid and base additives, the structures of the analytes and temperature were investigated.Experiments were performed at constant mobile phase compositions in the temperature range 10–50°C in order to study the effects of temperature, and thermodynamic parameters were calculated from plots of ln k or ln α vs. 1/T. Some mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes. It was found that the enantiomeric separations were in most cases enthalpically driven, but entropically driven separation was also observed. The sequence of elution of the enantiomers on the pseudo-enantiomerically behaving CSPs was determined in all cases.