Solvent effect on the conformational behaviour of amino acid and oligopeptide derivatives

The solvent effect on acetyl amino acid methyl esters and C- and N-protected di- and tripeptide derivatives has been studied in deuterium oxide (D2O), 1.1.1.3.3.3-hexafluoroisopropanol (HFiP), dimethyl sulfoxide (DMSO) and methylene chloride (CH2Cl2). The interpretation is based on the amide I region. For the amino acid derivatives the relative shift of the amide I signal clearly indicates the strength of the interaction with the solvent molecules. However, in HFiP and DMSO solutions the occurrence of two overlapping signals for the amide I and the ester carbonyl signal, respectively, indicates the existence of two major conformers. Knowing the solvent effects on the small amino acid esters allows the assignment of the signals in di- and tripeptide derivatives. Although the identification of turn structures in these flexible molecules is not possible, the band positions and intensity of the deconvoluted amide I region clearly shows that certain conformers can be stabilised. It can be concluded that the band profile in the amide I region is determined by the number of amino acid residues linked in the molecule, the bulkiness of the side chains and their sequence and to a major extend by the solvent properties.