Structural Consequences of N-Methylation of N-Terminus in Oligourea Foldamers

Oligourea foldamers fold into 2.5-helices. Most of the known modifications of the backbone, such as NH or CO group substitutions or incorporations of non-canonical residues, do not change the conformational properties of the resulting oligourea oligomers. In this study, we examined the structural influence of the methyl group, substituting NH protons in one or two residues at the N-terminus of the foldamer. Such N-methylated oligoureas appear to be helically folded with helix parameters determined from the crystal structure being almost the same as for non-methylated oligomers. Solution studies (CD, NMR) reveal that the backbone with N-Me urea groups is more flexible, but the urea group is still predominantly in trans,trans conformation. N-Methylation does not change the structural properties of oligourea foldamers, and thus may be a useful modification for modulating the strength of hydrogen bonds and intermolecular interactions.