Molecular Pharmacology, Vol 3, 487-494, Copyright © 1967 by the American Society for Pharmacology and Experimental Therapeutics

Molecular Orbital Calculation of Preferred Conformations of Acetylcholine, Muscarine, and Muscarone

¹ Battelle Memorial Institute, Columbus Laboratories, Biochemistry Division, Columbus, Ohio 43201

Using extended Hückel theory molecular orbital calculations, the preferred conformations of acetylcholine, L-(+)-muscarine, and D-(-)-muscarone have been predicted from total-energy minimization as a function of geometry. The calculations for muscarine and acetylcholine reveal a preferred conformation strikingly similar to conformations reported in the literature based upon crystal X-ray analysis. A comparison of calculated preferred conformations of L-(+)-muscarine and D-(-)-muscarone leads to the observation that the heteroatoms in the two molecules bear spatial relationships similar to each other. It is concluded that D-(-)-muscarone approaches the muscarinic receptor with the opposite face than does L-(+)-muscarine. From a consideration of the calculations on the three compounds, a complementary pattern of forces representing the muscarinic receptor is proposed.