A computational study of nicotine conformations in the gas phase and in water

The conformational preferences of nicotine in three protonation states and in the gas phase as well as aqueous solution are investigated using several computational procedures. Conformational aspects emphasized are N-methyl s tereochemistry, relative rotation of the pyridine and pyrrolidine rings, an d pyrrolidine ring conformation. All methods consistently predicted that th e N-methyl trans species are most stable for all protonation states in both gas phase and in water. However, the cis/trans energy gap is significantly reduced in water. Additionally, the two pyridine ring rotamers, which are energetically equivalent in the gas phase, experience different solvation e nergies in water.