Measurements of solubility and vapor pressure indicate that the cost o
f making a cavity in a nonpolar solvent that is large enough to accomm
odate a single water molecule is just balanced by the attraction betwe
en the water molecule and the walls of the cavity. As a result of this
unexpected coincidence, the equilibrium constant for entry of an isol
ated water molecule from the vapor phase into cyclohexane is almost ex
actly unity at room temperature. Molecules smaller than water prefer t
he vapor phase, whereas molecules larger than water prefer cyclohexane
. In equilibrium with liquid water, the tendency of single water molec
ules to enter small nonpolar cavities, such as may be present in mutan
t proteins, is expected to be vanishingly small.