DFT‐Aided Vibrational Circular Dichroism Spectroscopy Study of (−)‐S‐cotinine

Abstract The implementation of a strategy comprising the use of vibrational circular dichroism spectroscopy and DFT calculations allows determination of the solution‐state conformational distribution in (−)‐ S ‐cotinine, giving further proof of the extra conformer‐discriminating potential of this experimental technique, which may offer unique molecular fingerprints of subtly dissimilar molecular conformers of chiral samples. Natural bond orbital electronic structure calculations of the rotational barrier height between the two main conformers of the species indicate that hyperconjugative effects are the key force governing the conformational equilibrium. The negligible effect of the solvent’s polarity over both structure and conformational energy profile supports this result.