Control of Helix Formation in Vinylogous γ-Peptides by (E)- and (Z)-Double Bonds:  A Way to Ion Channels and Monomolecular Nanotubes

A complete overview on the alternative and competitive helices in vinylogous γ-peptides is given, which was obtained on the basis of a systematic conformational analysis at various levels of ab initio MO theory (HF/6-31G*, DFT/B3LYP/6-31G*, PCM/HF/6-31G*). Contrary to the parent γ-peptides, there is a strict control of helix formation by the configuration of the double bond between the C(α) and C(β) atoms of the monomer constituents. (E)-Double bonds favor helices with larger pseudocycles beginning with 14- up to 27-membered hydrogen-bonded rings, whereas the (Z)-configuration of the double bonds supports a distinct preference of helices with smaller seven- and nine-membered pseudocycles showing interactions between nearest-neighbor peptide bonds. The rather stable helices of the (E)-vinylogous peptides with 22-, 24-, and 27-membered hydrogen-bonded pseudocycles have inner diameters large enough to let molecules or ions pass. Thus, they could be interesting model compounds for the design of membrane channels and monomolecular nanotubes. Since (E)- and (Z)-vinylogous γ-amino acids and their oligomers are synthetically accessible, our study may stimulate structure research in this novel field of foldamers.