β ‑pinene is an optically active and racemic molecule, which presents in turpentine oils. It was demonstrated that when β‑pinene synergizes with paclitaxel, they can suppress lung carcinoma cells. The geometrical structure of β -pinene with chiral atom has big space steric hindrance, which is benefit for the synthesis of chiral foldamers. Therefore, a lot of study has been reported on enantio-selective ofβ ‑pinene derived molecular [7,8]. In 2017, the study that β ‑pinene-derived pyridyl group can induce the handedness of oligoamide foldamers has been reported[9]. Experimental data has shown thatβ -pinene-derived pyridyl connecting with quinoline oligoamide behave better selection of handedness at N-terminal than at C-terminals. They had investigated three types of foldamers, and thought that hydrogen bond should be an obvious factors of helical handedness. However, it is reported that hydrogen bonds, steric hindrance and electrostatics are responsible for the helical handedness either in the C-terminal or N-terminal in some works [10,11]. In order to reveal the intrinsic reason for better selection of helix-sense at N-terminal than at C-terminal, six experimental synthesized and two designed oligoamide foldamers substituted by β -pinene have been investigated in this paper. Six synthesized oligoamides include four foldamers containing β -pinene-derived pyridyl amine at the C-terminal (1a, 1b, 2a, and 2b) , two foldamers containing β - pinene-derived pyridyl carboxylic acid at the N-terminal (3a and 3b ). Two designed oligoamides include two foldamers containing three-center hydrogen bonds at N-terminal (4a and 4b ). Four types of foldamers (1-4 ) have been designed and they have been shown in Scheme 1. In foldamer 1–4 , na represents R chirality ofβ -pinene, nb represents S chirality of β -pinene. Because Zheng et al. have found that these foldamers are stable in chloroform (CDCl3), CDCl3 was selected as the solvent environment here. Based on the metadynamics simulations, the helical handedness of four types of foldamers withβ ‑pinene-derived pyridine has been calculated. From the data of the dihedral angle, rotation angle, and electronic orbitals constitutions of foldamers, the key factors of chiral induction toβ ‑pinene substituted foldamers have been analyzed and discussed.
Scheme 1. The structures of the foldamer 1–4
2. Results and Discussion
To obtain P or M helical bias of foldamers in the solvent, all investigated foldamers were put into a chloroform box. The metadynamics method was applied to investigate helical inversion of pentameric1–4 in chloroform, and force field parameters specifically were optimized for the arylamides containing quinoline-based. Computations were systematically performed on each enantiomer to assess their reproducibility.
2.1. Helix handedness of oligomers (1a/1b) substituted byβ -pinene-derived pyridyl amine at C-terminal