Metadynamics simulations on the key factors of handedness induction of quinoline oligoamide foldamers with a terminal chiral group

Metadynamics simulation has been used to determine the conformational energy landscapes of several helical quinoline oligoamides bearing β-pinene-derived pyridine at either the C or N-terminus. Based on the experimental results, the helix-sense preference for four types of foldamers with the chiral terminal group has been verified. To compare to the key factors inducing handedness to helix-sense preference, a terminal group with three hydrogen bond sites is designed and corresponding foldamers are built. The calculated results show that the delocalization effect and steric hindrance are mainly responsible for a particular helix-sense preference for the investigated foldamers. The more hydrogen bonds between the terminal group and oligoamide units are formed, the more stable foldamers are.