Thermodynamics and Kinetics of Chiral Separations with β‐Cyclodextrin Stationary Phase: II. Effect of Temperature and Pressure

Abstract

In this study, a series of coumarin‐based compounds is separated using a β‐cyclodextrin stationary phase with a polar‐organic mobile phase. Temperature and pressure are varied in order to observe the effects and determine important thermodynamic and kinetic parameters. Increasing the temperature decreases the retention and chiral selectivity, but increases the mass transfer rates for all chiral compounds. Increasing the pressure decreases the retention, but does not significantly affect the chiral selectivity. Van't Hoff plots of the natural logarithm of retention factor versus inverse temperature are linear with positive slopes, indicating an enthalpically favorable transfer from mobile to stationary phase. The second eluted enantiomer has a more negative change in molar enthalpy than the first, suggesting an enthalpically more favorable transfer. For all compounds, both the differential change in molar enthalpy and the differential change in molar entropy between the two enantiomers are negative. From these values, the compensation temperature is determined and is above ambient temperature, indicating an enthalpy‐driven separation. Although all the compounds have similar structures, different compensation temperatures are determined and enthalpy‐entropy compensation is not observed. This suggests that the retention mechanism is distinctly different. The change in molar volume is positive, indicating that the compounds occupy more space in the stationary phase than in the mobile phase and that inclusion in the cyclodextrin cavity does not occur to a significant extent. With regard to the kinetic behavior, the rate constants generally increase with increasing retention factor for the coumarin‐based solutes. However, the second eluted enantiomer has a surprisingly faster rate constant than the first enantiomer. The activation energy is positive, and the second eluted enantiomer always has larger activation energy than the first enantiomer. These thermodynamic and kinetic measurements provide a detailed and comprehensive view of the chiral retention mechanism.