These properties dictate the therapeutic, toxic, and metabolic characteristics of the over-
all drug molecule. These properties also completely control the ability of the drug to
withstand the arduous journey from the point of administration to the receptor site
buried deep within the body. These physical properties of drug molecules may be
categorized into the following major groupings:
- Physicochemical properties
- Shape (geometric, steric, conformational, topological) properties
- Stereochemical properties
- Electronic properties
Physicochemical properties are crucial to the pharmaceutical and pharmacokinetic
phases of drug action; the other three properties are fundamental to the pharmacody-
namic interaction of the drug with its receptor. Physicochemical properties (section 1.2)
reflect the solubility and absorption characteristics of the drug and its ability to cross
barriers, such as the blood–brain barrier, on its way toward the receptor. Geometric,
steric, and topological properties (section 1.3) and stereochemical properties (section 1.4)
describe the structural arrangement of the atoms within the drug molecule and influence
the geometry of approach as the drug molecule enters the realm of the receptor.
Electronic properties (section 1.5) reflect electron distribution within the drug molecule
and determine the nature of the precise binding interaction between the drug and its
receptor (by hydrogen bonding and various other forms of electrostatic interaction).
From the perspective of the drug designer, the electronic properties are among the most
DRUG MOLECULES: STRUCTURE AND PROPERTIES 23Figure 1.5 Bioisosteres. These are biologically equivalent molecular fragments that can be used to
replace portions of a drug molecule.