Continuum Solvation Model Could Explain Why Aqueous Phase Protonation of Nicotine and Nornicotine Occurs on the Pyrrolidine Nitrogen

The Continuum model of solvation IEF-PCM with UAHF or UAO cavity, helps to explain why nicotine and nornicotine protonated on nitrogen SP3 in aqueous phase. Graton et al have shown [1] that the site of protonation of nornicotine is the pyridine nitrogen in the gas phase (NSP2) and is a mixture (NSP2 and NSP3) for nicotine. In this work, we have calculated the free energies of salvation of both entities. The values obtained, show a better solvation of H+NSP3 form than H+NSP2 form either in nicotine or nornicotine. The geometrical parameters of neutral and protonated forms on NSP2 and NSP3 were determined. Significant change between the geometries in vacuo [2] and solvated is an elongation of the intramolecular hydrogen bond N1’…H2 (2.407 to 2.564 A) and (2.363 to 2.470 A) for Nicotine and nornicotine respectively. These calculations also showed a better solvation of H + SP3 in nornicotine than nicotine, which explains the highest