Crystal structures of cyclodextrin complexes with chiral molecules

Abstract

The chiral recognition by cyclodextrins and permethylated cyclodextrins have been investigated on the basis of the X-ray data of crystalline inclusion complexes. The macrocyclic ring of α- and β-cyclodextrin shows a round and symmetrical structure. α-Cyclodextrin includes racemic 1-phenylethanol with the statistical disorder of the hydroxyl group. A pair of the R- and S-isomers of flurbiprofen are included within the cylindrical cavity formed by dimeric β-cyclodextrin molecules with a head-to-head arrangement. The macrocyclic ring of permethylated cyclodextrins is remarkably distorted from the regular polygonal symmetry and has more flexibility in the conformational change than cyclodextrins. Owing to the distorted conformation and steric hindrance involving methyl groups, permethylated cyclodextrins do not equally include both isomers, as demonstrated by the permethylated α-cyclodextrin complexes with mandelic acids. Permethylated α-cyclodextrin binds D-mandelic acid more tightlyvia a host-guest hydrogen bond and induced-fit conformational change. Permethylated β-cyclodextrin forms a hydrated crystalline complex with R-flurbiprofen, but S-flurbiprofen forms a non-hydrated crystalline complex. Significant differences between the two complexes are found in the orientation of the phenyl group and hydrogen-bond formation involving the carboxyl group.