Ortho-halogen effects: n→π* interactions, halogen bonding, and deciphering chiral attributes in N-aryl glycine peptoid foldamers

Abstract

Noncovalent interactions play a prominent role in stabilizing the conformation and provide a fertile environment for crafting new structures. Here, we report our ensuing discovery of noncovalent interactions in N-aryl glycine peptoid foldamers emanate through the interaction between the ortho-halogen with the backbone tertiary amide carbonyl. N-aryl incorporating ortho-substituted halogens can facilitate simultaneous presence of n→π* interactions (C_aryl-X…C=O), and halogen bonding (C_aryl-X…O=C-) as established by computational modeling, and X-ray crystallography. We observed chiral features including pyramidalization of amide carbonyl carbon as n→π* signature, and stereogenic C_aryl-N chiral axis in N-aryl glycine peptoid dimers and a trimer. Inclusion and precise tuning of these noncovalent interactions in the structured peptoid oligomers would further promote the structure and dynamics of a predictable peptoid folding landscape.