Metadynamics Simulations on the Key Factors of Handedness Induction for
the N/C-Terminal Substituted Quinoline Oligoamide Foldamers
Caihua Zhou, * [a] Zhiwei Liu[b] Yannv Guo[c]
[a]School of Chemistry and Chemical Engineer, Xian
Yang Normal University, Xianyang, Shanxi, 712000,P.R. China.E-mail:xbdxzch@126.com
[b]Department of Chemistry &Biochemistry,
University of the Sciences in Philadelphia, Pennsylvania, USA.
[c] Institute of Physics, Northwest University,
Shanxi, 710000, P.R. China.
Keywords: Metadynamic, Helix, Chirality, Terminal group
Abstract: Metadynamics simulation has been used to describe 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, helix-sense preference
for four types of foldamers with the chiral terminal group has been
verified. To compare to the key factors of inducing handedness to
helical-sense preference, a terminal group with three hydrogen bond
sites is designed and corresponding foldamers are built. The calculated
results show the delocalization effect and steric hindrance 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.
1. Introduction
Today, foldamers represent a rapidly growing ensemble of molecules in
terms of diversity and chemical complexity. Foldamers can be as a bridge
between the molecular chirality and recognize of biological molecules.
Many reports have shown that foldamers display biomimetic properties on
reminiscent of allosteric proteins and receptor molecules[1-3]. Foldamers can translate chemical signals
into conformation changes, and hence into chemical outputs such as
control of reactivity and selectivity. Recent years, many potential
bioactive foldamers have been discovered, quinoline oligoamides have
been extensively demonstrated to adopt stable helical conformations in
various solvents. Dr. Liu and her group members had reported some
important foldamers with different terminal groups, and they found that
the helix-sense bias of foldamers can really be predicted by analysing
the interactions (hydrogen bond, steric and so
on)[4-6], and the chirality of terminal group
influences on the helix-sense of foldamers. A previous report found the
steric and hydrogen bonds have important influences on the helical
handedness of foldamer. So, it is benefit for the biological application
of foldamers by synthesizing new foldamers with bioactive terminal
group.