A Hybrid Mechanism in Chiral Discrimination Induced by Crystallization of Supramolecular Compounds

Host–guest complexes formed in aqueous medium
between permethylated
β-cyclodextrin (TMβ-CD) and racemic 1-(p-fluorophenyl)­ethanol (p-F-PE) are studied. The
crystalline complexes are characterized and their crystal structures
are determined, revealing two sets of solid phases with specific abilities
for chiral discrimination: on the one hand, a stable complete solid
solution with two independent complexes per asymmetric unit exhibits
a limited chiral recognition, and on the other hand, two metastable
partial solid solutions with unusual 1:2 host–guest stoichiometries
behave as diastereomeric complexes. The structural features of the
1:2 complexes and their study by means of molecular modeling show
that these solid phases, described as cocrystals formed between one
host–guest inclusion complex and one non-engulfed p-F-PE molecule, present a significant chiral discrimination occurring
both inside the cyclodextrin and outside the macrocycle in a crystal
lattice cavity. Therefore, the enantioselectivity observed in this
system results from an interplay between molecular inclusion in the
cyclodextrin and lattice inclusion. To our knowledge, it is the first
report of such a hybrid mechanism. An overview of the crystal structures
of the literature containing TMβ-CD is also achieved and allows
their classification in four structural groups in relation to their
crystal packing features.