Pharmaceutical Chemistry and Pharmacognosy
Structure drives behaviour
Functional groups predict ionisation, solubility and receptor fit. Carboxylic acids and amines ionise according to pKa, and the Henderson–Hasselbalch relationship tells you the ionised fraction at a given pH. Ionised species are more water-soluble and less membrane-permeable; unionised species cross lipid bilayers. LogP/logD estimates lipophilicity and predicts CNS penetration and hepatic metabolism. Stereochemistry matters: enantiomers can differ in potency and clearance (e.g. S-warfarin is the more potent enantiomer; levothyroxine versus dextrothyroxine).
Metabolism and prodrugs
Phase I reactions (oxidation, reduction, hydrolysis) introduce or expose polar groups; phase II reactions (glucuronidation, sulfation, acetylation, methylation, glutathione conjugation) increase water solubility for excretion. Prodrugs are designed to improve absorption or targeting and need bioactivation: enalapril to enalaprilat, valacyclovir to acyclovir, clopidogrel to its active thiol, omeprazole to the active sulfenamide in parietal cells.
Natural products
Know the major phytochemical classes and their signatures: alkaloids (nitrogen-containing, often basic - morphine, atropine, vincristine), glycosides (cardiac glycosides such as digoxin), terpenes/essential oils, and polyphenols. Herbal interaction traps: St John's wort induces CYP3A4 and P-glycoprotein; ginkgo and garlic increase bleeding risk; liquorice causes hypokalaemia and hypertension.
Worked example
For a weak acid with pKa 4.4 in plasma at pH 7.4, the ratio of ionised to unionised is 10^(7.4 − 4.4) = 1000:1 - essentially fully ionised, which is why weak acids are trapped in plasma relative to acidic gastric fluid.