The lack of intramolecular hydrogen bonding and the side chain effect in alanine conformers

Although amino acids are considered one of the most important classes of compounds found in Nature, the literature has few reports that have been made to understand the intramolecular interactions that govern their conformational energies and geometries. Actually, it has been arbitrarily assigned that possible intramolecular hydrogen bonding is the responsible force that dictates amino acid conformational preferences. In this paper, calculations at B3LYP/aug-cc-pVDZ level of theory within the NBO and QTAIM frameworks have shown that hyperconjugation and steric effects interplay, not H-bonding, are the intramolecular interactions that govern alanine conformational preferences. It is also shown that the steric interactions between the alanine methyl group side chain and its main chain influences its energies and geometries.

► Alanine conformational preferences in the isolated state were fully investigated. ► The lowest energy conformation is not stabilized by hydrogen bonding. ► Steric and hyperconjugative effects were analyzed for all conformers. ► Several theoretical methods were used to explain the conformational preferences.