[Crystallization and structural investigation of supramolecular compounds with modified cyclodextrins. Application to chiral discrimination]

Abstract

Among the numerous applications of cyclodextrins in separative sciences, organic synthesis, pharmacy and biotechnology, supramolecular host-guest complexation plays a major role due to the macrocyclic geometry of the host and the hydrophobic properties of the inner cavity. A less developed application of native or chemically modified cyclodextrins is their use for the preparative enantioseparation using co-crystallization methods. The intrinsic chirality of cyclodextrins enables the crystallization of diastereomeric compounds when the macrocyclic host interacts with a racemic mixture of the guest molecule. The preferential nucleation of one of these compounds, the amplification of the enantiomeric enrichment during the crystal growth and successive recrystallizations may lead to complete chiral separations. This alternative method of chiral discrimination is illustrated here with permethylated beta-cyclodextrin and (+/-)-1-(4-bromophenyl)ethanol. The results could be partially rationalized thanks to crystal growth studies and through the systematic determination of crystal structures by X-ray diffraction on single crystals. This study has shown that both inclusion geometries and crystal packing features determine the capability of modified cyclodextrins for chiral discrimination by crystallization.