Conformational structure of propranolol: A β-adrenergic blocking drug studied by NMR and PCILO methods

Abstract

The conformational structure of propranolol, a β-adrenergic blocking drug, has been investigated by pcilo calculations and 270-MHz proton nuclear magnetic resonance in D2O solution. The molecules coexist in at least two conformational states in solution with a low energy barrier. Both preferred conformations have extended structures which allow a three-point drug-receptor binding involving the aromatic moiety, the β-hydroxyl group, and -NH+2 groups of propranolol. The previously postulated “rigid” bicyclic structure does not exist to an appreciable extent in D2O solution.