The hydrophobic effect provides the thermodynamic driving force stabilizing the caged cholesterol. During formation of the ternary complex, water molecules comprising the solvent cage around cholesterol are released to the bulk solvent, along with five ordered water molecules from within the central cavity of each cyclodextrin. The number of waters in the central cavity is known from the crystal structure.

Summary

1. The high cohesiveness of water, which is due to hydrogen bonding, is central to the hydrophobic effect.
2. Water is more structured near nonpolar solutes, losing entropy to avoid the loss of hydrogen bonds.
3. The structure of water around nonpolar solutes at room temperature is surprisingly similar to that of bulk water, in that there is a tendency for water molecules to form pentagons around nonpolar groups.
4. The hydrophobic effect follows from the fact that water must be displaced from the surfaces of nonpolar (hydrophobic) molecules during association into complexes.
5. The central hydrophobic cavity of beta-cyclodextrin shows a high binding affinity toward cholesterol because the size, shape, and nonpolar character of the central cavity and cholesterol are a good match.
6. Usually, molecular association is made possible not by a single weak interaction but through the simultaneous cooperation of several weak interactions.