Chiral discrimination in the solid state

Abstract

The methods of enantiomeric resolution have been studied extensively, and involve the process of spontaneous resolution by crystallisation, diastereomer formation, enzymatic transformations and chromatographic methods. However, to our knowledge, no detailed study of the correlation between structure in the solid state and enantiomeric resolution has been carried out. We have taken a different approach to the question of enantiomeric resolution in order to understand the mechanism of the molecular recognition that drives the differentiation of the resolving agent for one particular enantiomer. A series of supramolecular systems was analyzed to investigate the mechanism of chiral discrimination in the solid state. We have set up a series of competition experiments where the resolving agent was exposed to mixtures of enantiomers, and the mole fraction of the starting mixture were varied systematically. The ensuing solutions were allowed to crystallise and the mole fraction of the entrapped enantiomer were measured by analysing the crystal structure. This is an extension of the technique employed to measure the selectivity prole of a given host compound (H) towards a pair of guests A and B, whereby the host, H is dissolved in a series of solutions where the mole fraction XA varies in steps from 0 to 1. The resulting crystals are analysed, yielding mole fractions of XA as ZA. The selectivity coefcient at each point is then defined as and is a measure of the discrimination of the host for a given guest. In our case the two guests were replaced by (R)- and (S)-enantiomers. One obtains more information regarding the resolution process when the selectivity is relatively poor and the targeted (R)- and (S)-enantiomers are both entrapped in the same crystal, although in different proportions. In this manner, one can assess the forces that impinge on both guests as they are entrapped in the crystal structure and the resultant conformation changes that occur in the host in order to best accommodate these guests.