Conformational Studies of Phe-rich foldamers by VCD spectroscopy and ab-initio calculations

Employing VCD spectroscopy, we demonstrate that the structural behaviour of the oligomers Boc-(L-Phe-L-Oxd)n-OBn are similar from n = 2 to n = 6; ab-initio calculations for the n=1 case provide physical insight into the conformational properties. Further information is gained by IR, 1H NMR and ECD spectroscopies; ECD spectra suggests the presence of different conformations between n = 1, on one side, and longer chain foldamers, on the other side. VCD and absorption IR spectra in methanol solutions can be interpreted as indicative of a PPII structure. In the case of Boc-L-Phe-L-Oxd-OBn, VCD spectra in CCl4 and detailed DFT computational analysis, allow one to demonstrate that the most populated conformers exhibit backbone dihedral angles similar to those of a PPII geometry. This is a remarkable outcome, as we had previously demonstrated that the Boc-(L-Ala-D-Oxd)n-OBn series folds in a band ribbon spiral, that is a subtype of the 310 helix.