Vibrational Circular Dichroism and Theoretical Study of the Conformational Equilibrium in (−)‐S‐Nicotine

Abstract

We report an extensive study of the molecular and electronic structure of (-)-S-nicotine, to deduce the phenomenon that controls its conformational equilibrium and to solve its solution-state conformer population. Density functional theory, ab initio, and molecular mechanics calculations were used together with vibrational circular dichroism (VCD) and Fourier transform infrared spectroscopies. Calculations and experiments in solution show that the structure and the conformational energy profile of (-)-S-nicotine are not strongly dependent on the medium, thus suggesting that the conformational equilibrium is dominated by hyperconjugative interactions rather than repulsive electronic effects. The analysis of the first recorded VCD spectra of (-)-S-nicotine confirmed the presence of two main conformers at room temperature. Our results provide further evidence of the hypersensitivity of vibrational optical activity spectroscopies to the three-dimensional structure of chiral samples and prove their suitability for the elucidation of solution-state conformer distribution.

Electronic absorption spectra of pyridine and nicotine in aqueous solution with a combined molecular dynamics and polarizable QM/MM approach

“…As observed in previous MD simulations on nicotine both in water and methanol, the most populated configurations are essentially related to the A and B conformers in agreement with the DFT computed PES, as Figure shows. Results of experimental measurements have been correctly interpreted on the basis of models with a similar relative population of the two conformers …”

Conformational properties of chiral tobacco alkaloids by DFT calculations and vibrational circular dichroism: (−)-S-anabasine

“…2:1 neat liquid and solution-state conformational composition, but unlike what was found for two chemically related species, namely, (−)-S-nicotine and (−)-Scotinine [37,38], neither the VCD nor the IR spectra enable us to observe any experimental feature distinctive of each one of the main conformers. The lower populations expected at room temperature for conformers m03 to m08 also prevented the observation of any sign of their presence.…”

“…Other authors have also pointed to the occurrence of this type of interaction in related systems such as nicotine (Ref. [37] and references therein), protonated nornicotine (Ref. [68]) and methyl substituted nicotinoid derivatives (Ref.…”

“…Intended to assess the conformational composition of the sample, both in pure phase and in solution, the study of the IR and VCD spectra below is mainly focused in the 1650-900 cm −1 region, where the most distinctive spectral features among the different conformers of the sample are expected to occur, as observed in other related systems previously studied by our group [37,38].…”

“…This technique represents one of the most sensitive forms of vibrational spectroscopy and has recently proven to be a more powerful conformer-discriminating tool than its non-chirality sensitive counterpart, FTIR, when studying the solution-state conformer distribution of other structurally related nicotinoids. [37,38] …”