Liquid Nicotine Tamed in Solid Forms by Cocrystallization

We address the problem of stabilizing liquid nicotine in solid forms at ambient conditions by cocrystallization. An intriguing aspect of nicotine lies in the fact that its crystal structure has never been reported in the literature, and this peculiarity may be ascribed to the liquid–glass transition that occurs when nicotine is supercooled under its melting point (−79 °C). Even though nicotine was considered a rigid molecule, its glass forming nature could be due to a certain extent of conformational variability, which has been assessed by a conformer search of the Cambridge Crystallographic Data Centre software. The design of cocrystals forms of nicotine is approached by analyzing its molecular electrostatic potential. On the basis of these considerations, three coformers have been identified, and their crystal structure shows that nicotine adapts to the packing features dictated by the coformers. The tool of packing energy frameworks has been used to discuss the stabilization of the cocrystals.