THE PRINCIPLE OF MAXIMUM CHIRAL DISCRIMINATION - CHIRAL RECOGNITION IN PERMETHYL-BETA-CYCLODEXTRIN

Five guest molecules, isomenthone, pulegone, 1-fluoro-1-phenylethane, 1-phenylethanol, and 2-methylbutanoic acid, binding to permethyl-beta- cyclodextrin, a chiral host molecule, have been simulated by molecular dynamics techniques. From the simulations we find the preferred bindi ng site to be the interior of the macrocyclic cavity. A new technique was used for locating the host's most enantiodiscriminating domain, wh ich was also found to be inside the macrocyclic cavity. It is conclude d that this particular host molecule displays its enhanced chiral disc riminating capacity because of this spatial coincidence. Also evaluate d in this paper are the types and magnitudes of intermolecular forces responsible for diastereomeric complexation and chiral discrimination; in both cases the short-range dispersion forces dominate. This study illustrates the ''principle of maximum chiral recognition'', the idea that maximum chiral recognition can be achieved by maintaining a spati al congruence between the host's domain of greatest enantiodifferentia tion with the guest's preferred binding site.