A structure-affinity study of the opioid binding of some 3-substituted morphinans

A ZINDO/1 quantum-chemical structure-affinity relationship study is presented for the interaction of a group of 3-substituted morphinans with mu, delta and kappa opioid receptors. From this and previous work it is concluded that: 1. Receptor selectivity is regulated by different electronic densities located sometimes at the same atomic center. 2. The equations for the binding to the three opiate receptors are consistent with previous results obtained for other kinds of opiate molecules. 3. Internal occupied molecular orbitals are very important in regulating receptor affinity (and selectivity). 4. The role of molecular orbitals in the saturated rings needs further analysis through the study of more molecular systems interacting with opiate receptors