difficult to predict and to engineer with insight into a molecule. Accordingly, extensive
use is now made of quantum mechanics and classical mechanics force field calculations
(section 1.6) to determine electronic and structural properties of drug molecules (before
the molecules are ever synthesized). Figure 1.6 summarizes the structural characteristics
of a drug molecule.
1.2 PHYSICOCHEMICAL PROPERTIES OF DRUG MOLECULES
All drug molecules interact with biological structures (e.g., biomembranes, the cell nucleus),
biomolecules (e.g., lipoproteins, enzymes, nucleic acids) and other small molecules on
their way “from the gums to the receptor.” Only by first unraveling the relatively simple
primary interactions between a drug molecule and the various molecular structures that
it encounters during its journey to the receptor can we understand drug activity at the
cellular and molecular level. Since all biological reactions take place in an aqueous
medium or at the interface of water and a lipid, the properties of water and this bound-
ary layer must be studied as part of a comprehensive understanding of the interaction
of a drug molecule with its receptor. Physicochemical properties reflect the solubility
characteristics of a drug (in both aqueous and lipid environments) and help to determine
the ability of a drug to penetrate barriers and gain access to receptors throughout
the body.
24 MEDICINAL CHEMISTRY
Figure 1.6 Properties of a drug molecule. A drug has many properties (size, shape, topology,
polarity, chirality) that influence its ability to interact with a receptor. Each of these properties is
required for the unique pharmacological activity of a drug molecule.