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 SP in aqueous phase. Graton et al have shown [1] that the site of protonation of nornicotine is the pyridine nitrogen in the gas phase (NSP) and is a mixture (NSP and NSP) for nicotine. In this work, we have calculated the free energies of salvation of both entities. The values obtained, show a better solvation of HNSP form than HNSP form either in nicotine or nornicotine. The geometrical parameters of neutral and protonated forms on NSP and NSP 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 Å) and (2.363 to 2.470 Å) for Nicotine and nornicotine respectively. These calculations also showed a better solvation of H + SP in nornicotine than nicotine, which explains the highest Pka of nornicotine (9.12) compared to nicotine (8.01). Keywords— Continuum, nornicotine, UAHF, UAO, Gsolvation