A central quantity in theories of the hydrophobic effect is the excess chemical
potential of a solute molecule,
, defined as the quasi-static work needed to bring
this molecule from the gas phase into the solvent. The connection between
and
the statistical properties of the neat solvent is provided by the potential distribution
theorem. [25] For a rigid solute:

where k is the Boltzmann constant, T is the temperature,
, Usol
is the solute-solvent potential energy and
abbreviates the
thermal average over insertions of the solute into thermally representative configurations
of the neat solvent. The extension of Eq. 1
to flexible solutes is available, [14] but it will
not be needed here.
If the solute is an impenetrable volume the exponential in the right side of Eq. 1 is either one or zero, depending on whether the solute
overlaps with van der Waals volumes assigned to solvent molecules. Then,
is
expressed simply as:

where p0 is the probability of successful insertion of the solute
into the solvent.
Consider insertions of a hard sphere solute into a liquid represented as hard spheres
or collections of hard spheres of one kind only. Their radius will be denoted as RS.
The extension to spheres of different sizes is straightforward. [18] In practice, the calculated quantity is the
probability distribution,
, that a randomly chosen point is at a distance
from the center of
the nearest solvent sphere. If
the radius of the largest solute that can
be inserted at this site is
. The probability p0(R)
can be obtained from pm(R) using the relation:

Two concrete methods for locating cavities of different sizes and calculating
were
described previously. [18, 26] Note that once positions of suitable cavities are
identified, they can be used as insertion sites for small spherical or nearly spherical
solutes to evaluate efficiently
for these solutes directly from Eq. 1. [20, 27, ] An implementation
of this approach is discussed in detail elsewhere. [26]
The third quantity of interest here is the density of solvent centers just outside the
solute (contact density),
, defined as: [19]

where
is the density of solvent and
is called the
contact correlation function. The last term in the right side of Eq. 4,
, is the average compressive force exerted by the
solvent on the cavity. Thus, the contact density is large in those solvents which squeeze
out a non-polar solute.
