From investigation of foldamer 1, 2 and 3, it is found
that the three-center hydrogen bonds between the terminal group and
oligomers are found both in 2 and 3, but the helical
selection is Figure 13. The FEP of 4a Figure 14. The structure
of 4a
better in 3 than in 2 . To further investigates the
relation between hydrogen bonds and helical
handedness of foldamers. We designed a
−NH2 connected
with pyridine ring of the terminal group (Scheme 1), and
−NH2 formed another hydrogen bond (N−H–O) with
quinoline amide. When this modifiedβ ‑pinene-derived pyridine
connects with N-terminal quinoline oligoamide, the foldamer 4were designed, and 4a/4b represents P-helix/M-helix. Based on
the metadynamic calculation, the FEP of 4a and 4b were
get. The results show that R chirality ofβ ‑pinene still induced the
P helix, S chirality still induced M helix. FEP shows that the
difference between the free-energy P-4a and M-4a is
6.7 kalmol-1, there is the bigger free-energy gap for4 than for 3 (Figure 13). When the R-chiral atom
induces the P type structure, the new hydrogen bond N−H–O is formed.
The bond length of N−H–O is 1.96 Å with bond angle of 150°. Thus,
together with two inherent three-center hydrogen bonds
(NQ–H−NA and
N∗–H−NA), there are three hydrogen
bonds in 4a (Figure 14). When the angle
∠NQ−CQ−C−NA is rotated,
which needs overcome a big free-energy barrier due to three hydrogen
bonds are destroyed. It is proved the more hydrogen bonds of the
terminal group, the more stability of foldamer 4 . In another
hand, the rotation of
∠NQ−CQ−C−NAcan induce another hydrogen bond
N–H−NA, the
hydrogen bond length is 1.789 Å,
the bond angle is 109°. So there should have a stable conformer4c (Supporting information S7). The distributions of dihedral
angle show the angle peaks of
∠NQ−CQ−C−NA at
±10°for (P)-4a/(M)-4b. And a
metastable state EPP also is found in FEP of 4a , the
minimum free-energy of EPP is 4.3kcalmol-1,
and it is similar to foldamer 3 . From the calculated data, it
can see that the
chiralβ ‑pinene connect with oligomers at N-terminal has the better
selection of helix than at the C-terminal. The reason mainly comes from
two aspects, one reason is that delocalization effect is found betweenβ ‑pinene derivatives with quinoline oligomers at N-terminal
(foldamer 3 and 4) , and the delocalization effect
improves the delivery of chirality, resulting in the better helical
selection of 3 and 4 than 1 and2 (β ‑pinene substituted at C-terminal). Another reason is
that β ‑pinene has big steric hindrance, it is difficult to rotate
between different helical handedness once there are more hydrogen bonds.
For foldamer 3a , the delocalized bond improved the selection of
chirality, delocalization effect is the key factors. The free-energy gap
of 4a became the bigger than that of 3a , which is due
to the more hydrogen bond to strengthen the helical stability of