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

• Steric/electrostatic factors determine the overall conformational distribution.
• Hyperconjugation controls the equilibrium between the two main rotamers.
• Increasing solvent’s polarity barely affects the conformational energy profile.
• Boltzmann weighted (2:1) DFT spectra match IR and VCD experimental profiles.

A thorough DFT and MM study of the conformational landscape, molecular and electronic structures of (−)-S-anabasine is reported aimed to reveal the mechanism controlling its conformational preference. Although the conformational flexibility and diversity of this system is quite extensive, only two structures are populated both in gas-phase and solution (CCl4 and DMSO). NBO-aided electronic structure analyses performed for the eight conformers representing minima in the potential energy surface of (−)-S-anabasine indicate that both steric and electrostatic factors are determinant in the conformational distribution of the sample in gas phase. Nonetheless, hyperconjugative effects are the key force tipping the balance in the conformational equilibrium between the two main rotamers. Increasing the polarity of the medium (using the IEF-PCM formalism) barely affect the conformational energy profile, although a slight increase in the theoretical population of those structures more affected by electrostatic interactions is predicted. The validity of the theoretical models and calculated conformers populations are endorsed by the accurate reproduction of the IR and VCD spectra (recorded in pure liquid and in CCl4 solution) of the sample (that have been firstly recorded and assigned in the present work) which are consistent with the occurrence of a 2:1 conformational ratio.

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