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.