Physicochemical Properties

of Drug

To Design Better Drugs:

Molecular Mechanism.

Drug action results from the interaction

of drug molecules with either normal or
abnormal physiological processes.
Drugs normally interact with targets
(which they are proteins, enzymes, cell
lipids, or pieces of DNA or RNA).

 Functional group contributions to the

physicochemical properties.

The ability of a chemical compound

to elicit a pharmacologic /therapeutic
effect is related to the influence of its
various
physical
and
chemical
(physicochemical) properties

Proper physicochemical parameters ensure

good drug action:
Pharmacokinetic properties:
Absorption.
Distribution.
Metabolism.
Excretion.
Pharmacodynamic properties:
Drug-receptor interaction:
o Activity.
o Toxicity.

Physicochemical Principles of Drug Action

The influence of the organic functional groups

within a drug molecule on:

Water solubility.
Lipid solubility.
Partition coefficient.
Acid-base properties.
Steric factors.
Stereochemistry.

Water solubility Versus Lipid solubility

Majority of drugs molecules possess

balanced solubility (have some degree of
solubility in both aqueous and lipid media).
Because in the biological system ,there is a
need for drugs molecules to move through
both aqueous (plasma, extracellular fluid,
cytoplasm, etc.) and lipid media (biologic
membranes).

Most Important Intermolecular Attractive

forces Involved in Solubilization

Van der Waals attraction.

Dipole-dipole attraction.
Ion-dipole bonding.

Van derWaals Attraction

Weakest intermolecular force (0.51.0 kcal/mole)

Electrostatic
Occurs between non polar groups
(e.g. hydrocarbons) .
Highly distance and temperature
dependent.

Dipole-Dipole Attraction
Stronger (1.0 to 10 kcal/mole).
Occurs electrostatically between
electron deficient and electron
excessive/rich atoms (dipoles).
Hydrogen bonding is a specific
example of this bonding and serves
as a prime contributor to
hydrophilicity.

 Why does an intramolecular hydrogen

bonding decrease water solubility?

Ion-Dipole Bonding
Electrostatic between a cation/anion
and a dipole.
Relatively strong (1-5 kcal/mole).
Low temperature and distance
dependence.
Important attraction between drugs
molecule and H2O.

Highly dissociable salts are more water soluble than

less dissociable ones.
Because the cation and anion must be able to
separate and interact with water molecules.
Highly dissociable salts are formed from:
strong acids with strong bases.
weak acids with strong bases.
strong acids with weak bases
Less dissociable salts are formed from:
weak acids with weak bases.