Cyclodextrin Nonrigidity

The very fast internal movement of native CyDs and of most of their derivatives, leading to the observation of averaged structures by most experimental techniques, is frequently overlooked. In addition to the temperature-dependent process of selfinclusion of substituent(s) [104-107], we were able to find only two studies of substituted CyDs in which movement of the macrocydes was at least partly frozen [104, 108]. Some other experimental results proving CyD flexibility using NMR 

On the basis of X-ray analysis, methylated or acetylated CyDs are sometimes considered to be more flexible than the native ones (see Chapter 7). Such a conclusion seems unfounded since X-ray diffraction can yield straightforwardly only the structure of the macrocyclic ring averaged over time and space, not its mobility. As a matter of fact, native CyDs are more flexible, and thus more difficult to freeze, than permethylated ones. This fact is frequently overlooked since the above mentioned averaging is not taken into account. As shown above, NMR spectra in solution and in the solid state are much more sensitive to CyD flexibUity and clearly prove their nonrigidity. 

---

Dodziuk, H (2002). Rigidity versns flexibility. A review of experimental and theoretical study pertaining to the cyclodextrin nonrigidity. Journal of Molecular Structure, 614, 33 5. 

---