Pharmaceutical Chemistry
Pharmaceutical chemistry spans inorganic, organic and medicinal chemistry; questions test functional groups, acid-base behaviour, stereochemistry, drug metabolism, prodrugs and structure-activity relationships.
Core rules
- Functional groups determine polarity, ionization and reactivity: carboxylic acids are acidic, amines basic, esters hydrolysable and phenols weakly acidic. Salt formation improves aqueous solubility.
- Stereochemistry matters: enantiomers are mirror images with identical physical properties except optical rotation; diastereomers differ in physical properties. Many drugs are chiral and one enantiomer may be more active or toxic.
- Medicinal chemistry links structure to action. Sulfonamides compete with para-aminobenzoic acid in bacterial folate synthesis; penicillins contain a beta-lactam ring; paracetamol overdose produces the toxic metabolite NAPQI.
Worked example
Enalapril is an ester prodrug. After oral absorption, ester hydrolysis converts it to enalaprilat, which inhibits angiotensin-converting enzyme. The prodrug improves oral bioavailability; the active metabolite is more polar and is largely excreted renally, so renal impairment requires dose review.
Traps
Do not call enantiomers identical in biological activity. Aromaticity requires a planar cyclic conjugated system with 4n+2 pi electrons. Do not ignore salt form when calculating dose: 500 mg amoxicillin trihydrate is not 500 mg anhydrous amoxicillin. Check whether a drug is a prodrug before predicting onset.