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

• Published in: Chemphyschem 2015-05, Vol.16 (7), p.1416-1427
• Main Authors: Rodríguez Ortega, Pilar G., Montejo, Manuel, Márquez, Fernando, López González, Juan J.
• Format: Article
• Language: English
• Subjects: (−)-S-cotinine; conformational landscapes; density functional calculations; molecular structures; Spectrum analysis; vibrational circular dichroism
• ISSN: 1439-4235; 1439-7641
• DOI: 10.1002/cphc.201500018

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. Conformation matters: Vibrational circular dichroism spectroscopy provides experimental proof of the incidence of a conformational mixture in solution‐state samples of (−)‐S‐cotinine. Natural bond orbital calculations suggest a major contribution of hyperconjugation effects in the barrier height, tipping the balance of the conformational equilibrium between the two main conformers.