The molecular conformation of the carboxyl group can be crucial for its chemical properties and intermolecular interactions, especially in complex molecular environments such as polypeptides. Here, we study the conformational behaviour of the model amino acid N-acetylproline in solution at room temperature with two-dimensional infrared spectroscopy. We find that the carboxyl group of N-acetylproline adopts two distinct conformations, syn- and anti-. In the syn-conformer the O–H group is oriented at ~60∘ with respect to the C=O and in the anti-conformer the O–H is anti-parallel to the C=O. In hydrogen-bond accepting solvents such as dimethyl sulfoxide or water, we observe that, similar to simple carboxylic acids, around 20% of the -COOH groups adopt an anti-conformation. However, when N-acetylproline is dissolved in a weakly hydrogen-bond accepting solvent (acetonitrile), we observe the formation of a strong intramolecular hydrogen bond between the carboxyl group in the anti-conformation and the amide group, which stabilizes the anti-conformer, increasing its relative abundance to ~60%.

Additional Metadata
Publisher Springer Nature
Funder NWO , ERC
Persistent URL dx.doi.org/10.1038/s42004-020-0329-7
Journal Commun. Chem
Citation
Giubertoni, G, Sofronov, O.O, & Bakker, H.J. (2020). Effect of intramolecular hydrogen-bond formation on the molecular conformation of amino acids. Commun. Chem, 3(1), 84: 1–84: 6. doi:10.1038/s42004-020-0329-7