Ab initio (4–31G) molecular orbital calculations were performed on model systems to investigate the proton-transfer version of the clastic binding hypothesis for opiate—receptor interactions. Ammonia was chosen as the model for the nitrogen-containing portion of the opiate molecule, while ammonia and water were chosen as models for the proton acceptor at the receptor. The equilibrium position of a proton situated between the two molecules is found to be determined primarily by the orientation of the proton-donor molecule with some influence also from the other molecule. Misalignments of the lone pairs can significantly alter equilibrium populations when the proton affinities of the two molecules are similar.
New Insights in the Clastic Binding Hypothesis for Opiate-Receptor Interactions. II. Proton-Transfer MechanismJournal of Pharmaceutical Sciences
Citation InformationNew Insights in the Clastic Binding Hypothesis for Opiate-Receptor Interactions. II. Proton-Transfer Mechanism V. M. Kolb and S. Scheiner J. Pharm. Sci., 1984 73, 719-723.