A Molecular Orbital Calculation of the Preferred Conformation of Nicotine

Using extended Huckel theory molecular orbital calculations, two equally preferred conformations of the nicotinium ion have been predicted from total energy minimization as a function of geometry. The calculated conformations are in good agreement with reported nuclear magnetic resonance (NMR)-predicted conformations of several nicotine derivatives. In only one predicted nicotinium ion conformation are there found to be two atoms, including the quaternary nitrogen atom, of comparable charge and interatom distance to those found in acetylcholine. Specifically these atoms in the nicotinium ion relate very closely to the quarternary nitrogen and carbonyl oxygen atoms of acetylcholine in its calculated preferred conformation. This observation permits time prediction that the two principal atoms necessary for nicotinic activity in the nicotinium ion are a quaternary nitrogen atom and a negatively charged atom about 4.85 A removed. As an adjunct to the study, an extended Huckel theory population analysis of acetylcholine in its calculated preferred conformation indicates a slightly negative total (σ + π) charge density on the ether oxygen atom.