Complementarity between a Target and Drug

The following listing and description of intermolecular forces is by no means exhaustive. It merely gives a general vocabulary for major types of forces encountered in medicinal chemistry discussions. The approximated energies associated with the various 

FIGURE 9.7 Effect of relative alignment on hydrogen bonding 

Organs and tissues in the body can have very different pHs. The pH of blood is 7.4. The stomach can be as low as 1, while the small intestine is slightly basic at about 8. Functional groups, especially carboxylic acids, can lose or gain a charge as they move from one part of the body to another. If the solution pH and pKa of the acid are known, then the relative concentrations of the acid and its conjugate base can be calculated through the Henderson-Hasselbalch equation (Equation 9.1). 

Determining the Ratio of a Conjugate Base to Its Acid at a Given pH 

PROBLEM Determine the ratio of benzoate (conjugate base) to benzoic acid (acid) in an aqueous solution at pH 7.0. The pKa of benzoic acid is 4.2. 

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Medicinal chemists have a distinct advantage in pursuing mechanism-of-action studies because it is possible to synthesize a series of structurally related congeners and measure their biological activity. A correlation between activity and particular structural features not only helps to identify the pharmacophore, or active moiety imbedded within the molecule, but also may establish critical requirements or complementarity for the biological target or receptor for the particular drug class. 

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