DYNAMIC BEHAVIOR OF A PERFUNCTIONALIZED BETA-CYCLODEXTRIN AS PROBED BY NMR AND MOLECULAR MODELING

Conformational analysis of a perfunctionalized beta-cyclodextrin by NM R and molecular modeling has revealed that this compound exists as an equilibrium mixture of C-1 and C-7 conformers in slow exchange. From c arbon chemical shifts, interglycosidic vicinal heteronuclear coupling constants and NOESY volumes, it has been demonstrated that the macrocy clic conformation is responsable for the asymmetry in the C-1 form. Se veral dynamic processes such as rapid conformational averaging, locali zed chemical exchange and the C-1/C-7 equilibrium have been shown to o ccur on widely separated timescales. In parallel, a molecular modeling study has revealed that the accessible conformational space of beta-C Ds is not significantly reduced with respect to that of the related di saccharide, beta-maltose. Al of the dynamic phenomena appear to be rel ated to the macrocylic puckering and two distinct modes of variation i n 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 puckerin g. Optimization of the NMR-defined theoretical structures leads to aut o-complexation of an exocyclic substituent. (C) 1997 Elsevier Science Ltd.