Conformational Studies of Phe-Rich Foldamers by VCD Spectroscopy and ab Initio Calculations

Abstract

Employing VCD spectroscopy, we demonstrate that the structural behavior of the oligomers Boc-(l-Phe-l-Oxd)_<i>n</i>-OBn is similar from <i>n</i> = 2 to <i>n</i> = 6; ab initio calculations for the <i>n</i> = 1 case provide physical insight into the conformational properties. Further information is gained by IR, ¹H NMR, and ECD spectroscopies. ECD spectra suggest 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)<i>_n</i>-OBn series folds in a β-band ribbon spiral that is a subtype of the 3₁₀ helix