Drug-Receptor Interaction I

Types of Binding Forces
Unless a drug comes into contact with
intrinsic structures of the body, it cannot
affect body function.
Covalent bond. Two atoms enter a
covalent bond if each donates an electron
to a shared electron pair (cloud).
This state is depicted in structural formulas
by a dash. The covalent bond is
“firm”, that is, not reversible or only
poorly so. Few drugs are covalently
bound to biological structures. The
bond, and possibly the effect, persist for
a long time after intake of a drug has
been discontinued, making therapy difficult
to control. Examples include alkylating
cytostatics or organophosphates
. Conjugation reactions
occurring in biotransformation also
represent a covalent linkage (e.g., to
glucuronic acid).
Noncovalent bond. There is no formation
of a shared electron pair. The
bond is reversible and typical of most
drug-receptor interactions. Since a drug
usually attaches to its site of action by
multiple contacts, several of the types of
bonds described below may participate.
Electrostatic attraction. A positive
and negative charge attract each
other.
Ionic interaction: An ion is a particle
charged either positively (cation) or
negatively (anion), i.e., the atom lacks or
has surplus electrons, respectively. Attraction
between ions of opposite
charge is inversely proportional to the
square of the distance between them; it
is the initial force drawing a charged
drug to its binding site. Ionic bonds have
a relatively high stability.
Dipole-ion interaction: When bond
electrons are asymmetrically distributed
over both atomic nuclei, one atom
will bear a negative, and its partner
a positive partial charge. The molecule
thus presents a positive and a negative
pole, i.e., has polarity or a dipole. A
partial charge can interact electrostatically
with an ion of opposite charge.
Dipole-dipole interaction is the electrostatic
attraction between opposite
partial charges. When a hydrogen atom
bearing a partial positive charge bridges
two atoms bearing a partial negative
charge, a hydrogen bond is created.
A van der Waals’ bond is
formed between apolar molecular
groups that have come into close proximity.
Spontaneous transient distortion
of electron clouds (momentary faint dipole)
may induce an opposite dipole
in the neighboring molecule. The van
der Waals’ bond, therefore, is a form of
electrostatic attraction, albeit of very
low strength (inversely proportional to
the seventh power of the distance).
Hydrophobic interaction. The
attraction between the dipoles of water
is strong enough to hinder intercalation
of any apolar (uncharged) molecules. By
tending towards each other, H2O molecules
squeeze apolar particles from
their midst. Accordingly, in the organism,
apolar particles have an increased
probability of staying in nonaqueous,
apolar surroundings, such as fatty acid
chains of cell membranes or apolar regions
of a receptor.