Structure--activity relationships of eseroline and morphine: ab initio quantum-chemical study of the electrostatic potential and of the interaction energy with water
Agresti, A.; Buffoni, F.; Kaufman, J.J.; Petrongolo, C.
Molecular Pharmacology 18(3): 461-467
1980
ISSN/ISBN: 0026-895X PMID: 7464812 Document Number: 155822
Ab initio SCF-MO-LCAO [self consistent field-molecular orbital-linear combination, F atomic orbitals] calculations of the electrostatic potential and analytical calculations of the interaction energy with water were performed for 2 analgesic molecules: eseroline and morphine. The nature of the calculations and the structure-activity relationships were discussed and the theoretical results were compared with the experimental binding affinities to the opiate receptor. The calculations show that the reactivity properties of the aminic N of eseroline and morphine are very similar, while significant differences were found for the electrostatic potential and water affinity of N5, benzene, and phenolic OH. These results can explain the lower binding affinity of eseroline to the receptor with respect to that of morphine, they agree with experimental data on the binding affinity of analgesics to the receptor and they confirm a molecular model of the analgesic-receptor interaction which was suggested on the basis of experimental data.