Resolution of non-racemic mixtures in achiral chromatographic systems: A model for, the enantioselective effects observed

Abstract Resolution of non-racemic samples in achiral chromatographic systems can occur when the solute undergoes self-association, e.g. , typically to dimers. In the resulting diastereomeric homo- and hetero-structures, the enantiomers are distributed in a non-symmetric fashion when the sample or sample fraction has an enantiomeric excess (e.e.) larger than 0%. In this paper, a new model for the resolution mechanism is presented. It takes into consideration that all molecules in the sample have capacity factors that are not constant during resolution, but change rapidly with time, owing to the rapid and reversible interconversion of monomers to dimers. Simple equations are given expressing the difference in the capacity factors of the enantiomers in a non-racemic environment on the basis of the time fraction spent by each of the antipodes in the form of the possible molecular species and their respective capacity factors. The process is thus represented in terms of the migration of the enantiomers. This approach leads to a better understanding of the resolution and of certain aspects of the order of elution. Different scenarios are considered with the dimerization taking place either only in the mobile or the solid phase or in both phases. Assuming that association normally also proceeds in the solid phase, both the “dimer distribution” and the “chiral layer” mechanisms can occur simultaneously. Their relative importance will vary with the experimental conditions. Analysis of the equilibrium concentrations showed that resolution can occur only if the dimers differ in stability.