On the probability of finding a water molecule in a nonpolar cavity

Measurements of solubility and vapor pressure indicate that the cost of making a cavity in a nonpolar solvent that is large enough to accommodate a single water molecule is just balanced by the attraction between the water molecule and the walls of the cavity. As a result of this unexpected coincidence, the equilibrium constant for entry of an isolated water molecule from the vapor phase into cyclohexane is almost exactly unity at room temperature. Molecules smaller than water prefer the vapor phase, whereas molecules larger than water prefer cyclohexane. In equilibrium with liquid water, the tendency of single water molecules to enter small nonpolar cavities, such as may be present in mutant proteins, is expected to be vanishingly small.