Pharmaceutical Chemistry: Inorganic, Organic and Medicinal Strands
What the domain tests
Pharmaceutical chemistry is examined in three strands - inorganic (pharmacopoeial salts and limit tests), organic (stereochemistry, mechanisms, functional-group analysis) and medicinal (structure–activity relationships, physicochemical properties, prodrug design, receptor interactions). Expect structure-identification items and short calculations rather than long essays.
Core rules to hold
- Limit tests: chloride gives opalescence with silver nitrate in dilute nitric acid compared against a standard; sulphate gives barium sulphate turbidity; heavy metals give a brown-black sulphide; arsenic is detected by the Gutzeit test, where arsine passed over mercuric chloride paper leaves a yellow stain.
- CIP priorities: higher atomic number first, so I > Br > Cl > F and O > N > C; among carbon groups –COOH > –CHO > –CH2OH > –CH3, which decides R/S.
- Bioisosterism: –OH/–NH2, –Cl/–CF3, –COOH/tetrazole, H/F substitutions retain activity while modifying metabolism or acidity.
- Prodrugs: enalapril to enalaprilat, sulfasalazine to 5-aminosalicylate in the colon, levodopa to dopamine across the blood–brain barrier.
- Hansch analysis: log(1/C) = k1 log P + k2σ + k3, with Hammett σ for electronic effects; an optimum log P near 2 suits oral and CNS penetration.
Worked example
Aspirin has pKa 3.5. In gastric juice at pH 1.5, the Henderson–Hasselbalch ratio [A−]/[HA] = 10^(1.5 − 3.5) = 0.01, so only about 1% is ionised and 99% remains unionised and membrane-permeable. At plasma pH 7.4 the ratio becomes 10^3.9, so the drug is almost entirely ionised and trapped - the basis of ion trapping.
Traps that cost marks
Recalling the Gutzeit stain as black rather than yellow; confusing R/S (absolute configuration) with d/l (direction of optical rotation); forgetting that log P refers to the unionised species; assuming organic acids stay unionised at plasma pH.