New insights in the clastic binding hypothesis for opiate-receptor interactions II: Proton-transfer mechanism.

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.