The Thermodynamics of Chromatography - Other Thermodynamic Methods that are Used for Studying Chromatographic Systems > Optimum Operating Conditions for Chiral Separations in Liquid Chromatography > Page 61


It is clear that there is yet another limitation of which to be aware when exploring the effect of solvent composition on retention and selectivity. It is important to examine the effect of solvent composition over a range of temperatures, to ensure that the true effect of solvent composition on selectivity is disclosed. If the distribution system is evaluated at, or close to that temperature where the separation ratio remains constant and independent of solvent composition, then the potential advantages that can be gained from an optimized solvent mixture will never be disclosed. Any evaluation of either a particular stationary phase, or solvent mixture, for the separation of closely eluting solutes must be carried out over a range of temperatures.



Optimum Operating Conditions for Chiral Separations in Liquid Chromatography

Thermodynamic reasoning need not be used exclusively to examine a chromatographic problem but can also be employed together with other aspects of chromatography theory to achieve a practical goal. The following example shows how thermodynamics can be used with appropriate optimizing equations to identify the optimum conditions for particular difficult types of separation.

In gas chromatography (GC), chiral selectivity is controlled by choice of stationary phase and operating temperature. From a practical point of view, chiral selectivity is achieved by introducing spatially oriented groups into the stationary phase molecules and, as a consequence, an additional entropic component to the standard energy of distribution. Physically, by choosing the right structure, a closer interaction of one solute enantiomer with the stationary phase, relative to that of the other can be achieved. This favored closer contact will result in stronger interactions between the chemical groups of that particular isomer and the neighboring groups on the stationary phase. As a consequence, both the entropic enthalpic contributions to the standard energy will be increased. Because the enthalpic contribution to the standard energy is temperature dependent, and the magnitude of the standard enthalpy of the two enantiomers will differ (irrespective of the nature of the stationary phase) the two curves relating Log(V') against 1/T must intersect (note bene the standard enthalpy is proportional to the slope of the curve relating the logarithm of the corrected retention volume to the reciprocal of the absolute temperature) Consequently, there must be a temperature at which the enantiomers co-elute and, in general, the chiral selectivity must also be temperature dependent,  However, the co-elution temperature may, or may not, fall in the practical temperature range of the separation and conequently may not be observable. In LC, the same situation exists, except that a third variable is present that controls retention and selectivity, and that is the composition of the mobile phase.