Dynamic behavior of a perfunctionalized β-cyclodextrin as probed by NMR and molecular modeling

Conformational analysis of a perfunctionalized β-cyclodextrin by NMR and molecular modeling has revealed that this compound exists as an equilibrium mixture of C1 and C7 conformers in slow exchange. From carbon chemical shifts, interglycosidic vicinal heteronuclear coupling constants and NOESY volumes, it has been demonstrated that the macrocyclic conformation is responsable for the asymmetry in the C1 form. Several dynamic processes such as rapid conformational averaging, localized chemical exchange and the C1C7 equilibrium have been shown to occur on widely separated timescales. In parallel, a molecular modeling study has revealed that the accessible conformational space of β-CDs is not significantly reduced with respect to that of the related disaccharide, β-maltose. All of the dynamic phenomena appear to be related to the macrocylic puckering and two distinct modes of variation in puckering have emerged from MD trajectories: transitions are either auto-compensated without perceptible change in macrocycle puckering or irreversible leading to considerable variation in macrocycle puckering. Optimization of the NMR-defined theoretical structures leads to auto-complexation of an exocyclic substituent.