Molecular Symmetry of Permethylated β-Cyclodextrins upon Complexation

The C-n molecular symmetry implicated by the schemes with which cyclodextrins (CDs), the well-known cyclic oligosaccharides, are introduced in the literature, is not valid. Numerous studies have shown that CDs are rather flexible with their macrocycle adopting various conformations that enable the inclusion complexation of guest molecules of various shapes. In this work, the loss and gain of the C-7 symmetry of the heptakis (2, 3, 6-tri-O-methyl)-beta-CD (TM-beta-CD) is investigated by means of its conformation geometrical features in its hydrated form and upon complexation with molecules of different shapes. For this, the crystal structure of the inclusion complex of a bulky guest molecule (giberellic acid) in TM-beta-CD is presented for the first time and compared with the previously determined crystal structures of monohydrated TM-beta-CD and the inclusion complex of a linear monoterpenoid (geraniol) in TM-beta-CD. The structural investigation was complemented by molecular dynamics simulations in an explicit solvent, based on the crystallographically determined models. The crucial role of the guest, in the symmetry gain of the host, reveals a pronounced induced-fit complexation mechanism for permethylated CDs.