A detailed VCD spectroscopic analysis of well-selected chiral model systems can give valuable and unprecedented insights into intermolecular interactions such as solvation or reactant–substrate binding in catalysis.

The three-dimensional structure of a peptide is strongly influenced by its solvent environment. In the present study, we study three cyclic tetrapeptides which serve as model peptides for β-turns. They are of the general structure cyclo(Boc-Cys-Pro-X-Cys-OMe) with the amino acid X being either glycine (1), or L- or D-leucine (L- or D-2). Using vibrational circular dichroism (VCD) spectroscopy, we confirm previous NMR results which showed that D-2 adopts predominantly a β_II turn structure in apolar and polar solvents. Our results for L-2 indicate a preference for a β_I structure over β_II. With increasing solvent polarity, the preference for 1 is shifted from β_II towards β_I. This conformational change goes along with the breaking of an intramolecular hydrogen bond which stabilizes the β_II conformation. Instead, a hydrogen bond with a solvent molecule can stabilize the β_I turn conformation.