LOCATING REGIONS OF MAXIMUM CHIRAL DISCRIMINATION - A COMPUTATIONAL STUDY OF ENANTIOSELECTION ON A POPULAR CHIRAL STATIONARY-PHASE USED IN CHROMATOGRAPHY

The concept of maintaining spatial congruence between substrate bindin g site and regions of greatest enantiodifferentiation to ensure effici ent chiral recognition in host-guest chemistry is described in this pa per. Regions of maximum chiral recognition were located by determining Boltzmann weighted intermolecular energies of chiral probe molecules placed at well-defined grid points around a molecule and then evaluati ng the magnitude of (dis)similarity of interaction at each grid point. Sites having little or no energy differences between enantiomeric pro bes are nondiscriminatory while those of greatest energy difference co rrespond to regions of maximum chiral discrimination. Seven analyte mo lecules containing a diverse set of organic functional groups were eva luated when binding to permethylated beta-cyclodextrin, a popular chir al stationary phase used in chromatography. The preferred binding site for host-guest association is the interior of the cyclodextrin, and t he region of maximum discrimination is found to coincide with this loc ation for all analytes studied. Forcing the guests to bind to the exte rior of the macrocycle by blocking the interior of the cyclodextrin is predicted to reduce or eliminate resolution. A literature report conf irming this prediction is cited.