Molecular orbital studies on the mechanism of drug-receptor interaction. 5. Molecular reactivity and receptor affinity of beta-agonist adrenergic drugs.

The electrostatic molecular potential (EMP) of model compounds (isoproterenol and four of its analogs) with agonist activity on the beta-adrenergic receptor was investigated, at the SCF-MO ab initio level. A method was developed to calculate the drug-receptor interaction energy (delta E) for these compounds, and the EMP and delta E values were compared with the affinity of the drugs for the beta-adrenergic receptor, quantified in terms of pKd. Our results indicate that the aromatic ring takes part in its entirely in the interaction with the receptor. No particular constituent of the aromatic portion considered by itself appears to play a determining role in this interaction.