RESOLUTION OF NON-RACEMIC MIXTURES IN ACHIRAL CHROMATOGRAPHIC SYSTEMS- A MODEL FOR THE ENANTIOSELECTIVE EFFECTS OBSERVED

Resolution of non-racemic samples in achiral chromatographic systems c an occur when the solute undergoes self-association, e.g., typically t o dimers. In the resulting diastereomeric homo- and hetero-structures, the enantiomers are distributed in a non-symmetric fashion when the s ample or sample fraction has an enantiomeric excess (e.e.) larger than 0%. In this paper, a new model for the resolution mechanism is presen ted. 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 o f monomers to dimers. Simple equations are given expressing the differ ence in the capacity factors of the enantiomers in a non-racemic envir onment on the basis of the time fraction spent by each of the antipode s in the form of the possible molecular species and their respective c apacity factors. The process is thus represented in terms of the migra tion of the enantiomers. This approach leads to a better understanding of the resolution and of certain aspects of the order of elution. Dif ferent scenarios are considered with the dimerization taking place eit her 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 si multaneously. Their relative importance will vary with the experimenta l conditions. Analysis of the equilibrium concentrations showed that r esolution can occur only if the dimers differ in stability.