with free, nonbonding electron pairs. Acceptor molecules are p-electron-deficient systems
such as purines and pyrimidines or aromatics with electron-withdrawing substituents
(e.g., picric acid).
A classic example of CT complex formation occurs in the solution of iodine (an
acceptor) in cyclohexene (a donor), when the solution assumes a brown color due to a
shift in its absorption spectrum. The brown is not a color in the physical sense, but
rather the result of a very broad absorption band encompassing about 200 nm in the vis-
ible spectrum and evolving as a result of electronic changes in the CT complex. In con-
trast, a solution of iodine in CC1 4 —an inert solvent—is purple.
Drug–receptor interactions often involve CT complex formation. Examples include
the reactions of antimalarials with their receptors and of some antibiotics that interca-
late with DNA. The CT energy is proportional to the ionization potential of the donor
and the electron affinity of the receptor, but is usually no higher than about 30 kJ/mol.
2.3.6 Dispersion and Van der Waals InteractionsVan der Waals bonds exist between all atoms, even those of noble gases, and are based
on polarizability—the induction of asymmetry in the electron cloud of an atom by a
nucleus of a neighboring atom (i.e., a positive charge). This is tantamount to the
induced formation of a dipole. However, although the interaction: between induced
dipoles sets up a temporary local attraction between the two atoms, this noncovalent
interaction decreases very rapidly, in proportion to 1/R^6 ,whereRis the distance sepa-
rating the two molecules. Such van der Waals forces operate within an effective distance
of about 0.4–0.6 nm and exert an attractive force of less than 2 kJ/mol; therefore, they
are often overshadowed by stronger interactions. While individual van der Waals bonds
make a very low energy contribution to a system, a large number of van der Waals
forces can add up to a sizable amount of energy.
2.3.7 Hydrophobic InteractionsHydrophobic binding plays an important role in stabilizing the conformation of proteins,
in the transport of lipids by plasma proteins, and in the binding of steroids to their recep-
tors, among other examples. The concept of these indirect forces, first introduced by
Kauzman in the field of protein chemistry, also explains the low solubility of hydrocar-
bons in water. Because the nonpolar molecules of a hydrocarbon are not solvated in
water, owing to their inability to form hydrogen bonds with water molecules, the latter
become more ordered around the hydrocarbon molecule, forming a molecular level
interface that is comparable to a gas–liquid boundary. The resulting increase in solvent
structure leads to a higher degree of order in the system than exists in bulk water, and
therefore a loss of entropy. When the hydrocarbon structures—whether two protein side
chains or hexane molecules dispersed in water—come together, they will “squeeze out”
the ordered water molecules that lie between them (figure 2.1). Since the displaced
water is no longer part of a boundary domain, it reverts to a less ordered structure,
which results in an entropy gain. This change is sufficient to improve the free energy
of the system by about 3.4 kJ/mol for every methylene group, and is tantamount to a
bonding energy because it favours the association of hydrophobic structures. Naturally,
RECEPTORS: STRUCTURE AND PROPERTIES 73