title: The Principle of Maximum Chiral Discrimination: Chiral Recognition in Permethyl-beta-cyclodextrin.
abstract: 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 binding site to be the interior of the macrocyclic cavity. A new technique was used for locating the host's most enantiodiscriminating domain, which was also found to be inside the macrocyclic cavity. It is concluded that this particular host molecule displays its enhanced chiral discriminating capacity because of this spatial coincidence. Also evaluated 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 spatial congruence between the host's domain of greatest enantiodifferentiation with the guest's preferred binding site.
authors.affiliation: Department of Chemistry, Indiana University-Purdue University at Indianapolis (IUPUI), 402 North Blackford Street, Indianapolis, Indiana 46202.
authors.forename: Kenny B.
authors.initials: KB
authors.lastname: Lipkowitz
authors.forename: Robert
authors.initials: R
authors.lastname: Coner
authors.forename: Michael A.
authors.initials: MA
authors.lastname: Peterson
authors.forename: Antonio
authors.initials: A
authors.lastname: Morreale
authors.forename: Jason
authors.initials: J
authors.lastname: Shackelford