Deciphering C–H⋯O/X weak hydrogen bonding and halogen bonding interactions in aromatic peptoids

Abstract

Previous strategies of peptoid folding have focused on identifying single dominant interactions, whereas peptide research has shown that identifying multiple, weak, and cooperative interactions might be a better strategy to understand folding. Towards this goal, a few such interactions have been deciphered in this work, including intramolecular C–H⋯O/X weak hydrogen bonding interactions and N–H⋯N type hydrogen bonding. We also deciphered intermolecular C–X⋯O halogen bonding in the aromatic peptoid model systems. Both intramolecular and intermolecular weak interactions have been evaluated by X-ray crystallography and computational modeling. These interactions bias ω-dihedral angle in the trans configuration, as evaluated by NMR spectroscopy in the solution phase and the solid-state via X-ray crystallography. We established that fixing the ω-dihedral in the trans-amide configuration leads to the identification of the web of weak noncovalent interactions that are otherwise non-trivial to decipher. This new design strategy elucidates the control of peptoid amide isomerization that might be needed to access new secondary structures, facilitating the better mimicking of peptides.