Thermodynamic Principles of Enantiomer Separation

Analytical-scale enantiomer separations on CSPs are usually carried out under linear (non-overloaded) chromatographic conditions, under which the retention of the individual enantiomers can be expressed as 

The chromatographic enantioselectivity Kr s is given by the ratio of the retention factors observed for the individual enantiomers. 

By convention, apis calculated by dividing the retention factor of the more retained enantiomer by that of the less retained enantiomer (kR kg). 

During the chromatographic process, the reversible binding (and release) of enantiomers from the mobile phase to SO sites in the CSPs is usually fast relative to the chromatographic time scale, and is essentially under thermodynamic control. The magnitude of aR s can be related to the difference of the free energies (AAGr s) of the diastereomeric association equilibria between chiral SO and the SAs 

Equation (7.4) imphes that useful levels of enantiomer separation may even be achievable with very small AAGr s-values. For example, at ambient temperature (298 K) a free energy difference as small as 240 J mol corresponds to aR s = 1.1, a selectivity that may suffice to achieve baseline separation of enantiomers, even on moderately efficient chromatographic systems. 

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