Many supramolecular chemistry texts (1)(2) have described the structure of cyclodextrins. Most commonly used is the tapered cylinder model, which has a narrow face and a wide face, referred to as the primary and secondary faces, respectively. The primary face comprises the primary hydroxyl groups, and the secondary faces comprises the $\ce{—CH2OH}$, or the secondary hydroxyl groups. All hydroxyl groups are exocylic, leaving the internal cavity wall primarily made up of C-C and C-H bonds. It is this cavity, along with the exocylic hydroxyls, that allows for cyclodextrin to function the way it does, creating hydrophobic micro-domains within an aqueous solution, and polar domains which associate with water. The figure below should help visualize the structure better (taken from 3).
The cyclodextrins have been investigated for a long time, and many non-polar guests have been hosted to create simple inclusion complexes and rotaxanes with them. This is not to say that polar molecules cannot associate within the cavity of the cyclodextrins. In fact, as you rightly point out, hydrates of cyclodextrin most certainly exist. In an aqueous solution with no guest molecules, the inner cavity is filled with water molecules, which has been confirmed with diffraction and crystallization studies (4). The inner ring is majorly hydrophobic. It is just that polar molecules like water do not associate with the cyclodextrin cavity in the same way as non-polar molecules do.
The water 'hosting' appears to be strongest at the narrow side where electron density is highest, but primarily stabilized by water-water H-bonding, not primarily because of water-wall interactions (5). Non-polar molecules on the other hand, will associate through every kind of host-wall forces: dispersion, dipole, and H-bonding. The closer the size of the guest to the size of the host's cavity, the greater the number and strength of the interactions — an effect called complementarity, which forms the basis for all supramolecular chemistry. The effect of complementarity is profound, described by many authors (1)(2)(J. M. Lehn also emphasizes its importance in his lectures and books), also observed in the theoretical study that Karsten linked (7). This is the effect of the ring.
It is because these electron densities are high primarily at the rim that the inclusion of polar molecules like water is not particularly strong, as they do not have complete hydrogen bonding to all centers (see above; figure taken from (6)), nor are they particularly similar in size to that of the cavity (i.e., they have low complementarity). Thus, when an appropriately-sized non-polar molecule (for example, benzene) is also in aqueous solution, the displacement of the (relatively) loosely-bound water molecules and the inclusion of the non-polar guest occurs. The combination of interactions (dispersion forces, dipole interactions, H-bonds) and the effect of complementarity between host-guest molecules results in the complexation of non-polar substrates being favored in an aqueous solution.
- Ariga, K., Kunitake, T.; Supramolecular Chemistry — Fundamentals and Applications, Sect. 2.7: Cyclodextrin – A Naturally Occurring Cyclic Host, Springer, 2006, pp. 21
- Steed, J. W., Atwood, J. L.; Supramolecular Chemistry, Sect. 6.3: Cyclodextrins, 2nd Ed., Wiley, 2009.
- Battle, C. H., Jayawickramarajah, J.; Supramolecular Approaches for Inhibition of Protein–Protein and Protein–DNA Interactions, Wiley, 2012.
- Saenger, W. et al.; "Structures of the Common Cyclodextrins and Their Larger Analogues — Beyond the Doughnut." Chem. Rev., Vol. 98, Issue 5, 1998.
- Pereva, S., Nikolova, V., Angelova, S., Spassov, T., Dudev, T.; Beilstein J. Org. Chem., Vol. 15, 2019.
- Sandilya, A. A., Natarajan, U., Priya, M. H.; ACS Omega, Vol. 5, No. 40, 2020.
- Chen, W., Chang, C. E., Gilson, M. K.; Biophys J., Vol. 87, No. 5, 2004.
