Halogen Bonding Directed Supramolecular Quadruple and Double Helices from Hydrogen-Bonded Arylamide Foldamers

Article abstract of DOI:10.1002/anie.201811561

Halogen bonding has been used to glue together hydrogen-bonded short arylamide foldamers to achieve new supramolecular double and quadruple helices in the solid state. Three compounds, which bear a pyridine at one end and either a CF₂I or fluor

Full text of DOI:10.1002/anie.201811561

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Accepted Article
Title: Halogen Bonding-Directed Supramolecular Quadruple and
Double Helices from Hydrogen Bonded Arylamide Foldamers
Authors: Chuan-Zhi Liu, Satish Koppireddi, Hui Wang, Dan-Wei Zhang,
and Zhan-Ting Li
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201811561
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Halogen Bonding-Directed Supramolecular Quadruple and
Double Helices from Hydrogen Bonded Arylamide Foldamers
Chuan-Zhi Liu,[a]+ Satish Koppireddi,[a]+ Hui Wang, Dan-Wei Zhang * and Zhan-Ting Li*
[a]
[a],
[a]
Dedicated to Professor Qing-Yun Chen for his 90th birthday.
Abstract: Halogen bonding has been used to glue hydrogen bonded short
arylamide foldamers to achieve new supramolecular double and quadruple
helices in the solid state. Compounds 1-3, which bear one pyridine at one
generation of long supramolecular double helical structure.
However, to the best of our knowledge, such a strategy has never
been reported. Previously, metal-coordination, hydrogen bonding,
and I interaction have been utilized to induce supramolecular
end and one CF
induced by head-to-tail NI halogen bonding to form one-component
supramolecular and helices, which further stack to afford
2
I or fluorinated iodobenzene group at the other end, are
[
13]
single helices from oligo(m-phenylene ethynylene)s, arylamide
foldamers,[ or amidothiourea derivatives, respectively. It has
been well-established that halogen bonding and hydrogen
bonding are able to orthogonally co-drive the generation of a
variety of advanced supramolecular architectures.[16] Herein, we
describe that intermolecular NI halogen bonding can be used to
“glue” short arylamide foldamers into supramolecular single
helices. We demonstrate that the new self-assembled helices are
able to further stack to form more complicated supramolecular
double and even quadruple helical structures.
14]
[15]
P
M
supramolecular double-stranded helices. Double helix formed by 3 can
further dimerize to form a G-quadruplex-like supramolecular quadruple
helix. Symmetric compound 4, which bears two pyridines at the ends, is
revealed to bind to ICF
component supramolecular P and M helices, with one turn consisting of four
2+2) molecules. Half of the molecules of 4 in two P helices and two M
2 2
CF I (5) through NI halogen bonding to form two-
(
helices are found to stack alternately to form another supramolecular
quadruple helix. Another half of the molecules of 4 in such quadruple helices
stack alternately with counterparts from neighbouring quadruple helices,
leading to unique quadruple helical arrays in the two-dimensional space.
Compounds 1-4 were prepared for this study. 1-3 bear one
pyridine at one end and one CF I or iodobenzene group at the
2
other end, which were designed to form head-to-tail IN halogen
bonding, whereas symmetric 4 contains two pyridines at the ends
to form intermolecular NI halogen bonding with 5. The arylamide
backbones are fully hydrogen bonded and thus were expected to
form hydrogen bonded crescent conformation.[17] The pyridine N
Since the discovery of the double helical structure of DNA by
Watson and Crick,[1] chemists have been attracted to design
simple linear molecules that are able to form artificial double
helices.[ Currently, a variety of oligomeric backbones have been
prepared that can produce short double helical structures
2]
atom is a strong halogen bonding acceptor, whereas the I atom
on fluorinated aryl or alkyl groups are typical halogen bonding
stabilized by metal-coordination,[
3]
hydrogen bonding,
[4]

[18]
donors. For all the compounds, i-butyl groups were introduced
stacking,[ or electrostatic attraction.[6] Jiang and Huc also
reported the generation of a quadruple helix from a tetrameric
quinolineamide.[7] However, many DNAs have long sequences of
hundreds to millions of nucleotides, which are prerequisite for the
evolution of various advanced functions.[8] The development of
synthetic systems for the creation of long double helices is not
only fundamentally valuable, but also provide new opportunities
for finding new properties or functions that are not available for
short analogues. In this category, examples of polymeric double
helices have been reported.[9] Previously, halogen bonding has
also been used to induce several molecular components into
single to triple helical structures.[10-12] Nevertheless, the realization
of accurate helical conformation of large aromatic backbones is
still a challenge. It was envisioned that efficient control of the
head-to-tail connection of a short double helix would lead to the
5]
to endow reasonable solubility and good crystallinity.[19]
1
3
The H NMR spectra of compounds 1-4 in CDCl showed a set
of signals of high resolution (Figures S1-S4), indicating that no
important aggregation took place. Their NH signals all appeared
in the downfield area (>9.04 ppm), which confirmed that they were
all involved in intramolecular NHO hydrogen bonding and thus
the formation of a crescent conformation for the backbones, as
[
a]
C.-Z. Liu, Dr. S. Koppireddi, Dr. H. Wang, Prof. D.-W. Zhang, Prof.
Z.-T. Li
Department of Chemistry, Shanghai Key Laboratory of Molecular
Catalysis and Innovative Materials, and Collaborative Innovation
Centre of Chemistry for Energy Materials (iChEM)
Fudan University
[
20]
established for the prototypical arylamide sequences.
I group,[
17d]
revealed the
2205 Songhu Road
Crystals of 1, which bears a NHCOCF
2
Shanghai 200438 (China)
E-mail: zhangdw@fudan.edu.cn, ztli@fudan.edu.cn
These authors contributed equally.
formation of two conformal enantiomers in the crystal due to the
distortion of the aromatic backbone (Figure 1a). As expected, the
NH protons all formed strong intramolecular NHO hydrogen
bonding, which rigidified the backbone to adopt a crescent
shape.[20] Both conformers formed strong head-to-tail IN
[
+]
Supporting information for this article is given via a link at the end of
the document.
1
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halogen bonding (IN distance: 2.81 Å, the sum of the van der
Waals radium of I and N: 3.53 Å; CIN angle: 178.6), which led
to the formation of supramolecular one-component P and M
helices (Figure 1b). The CIN angle was close to 180, which
further supported the attractive interaction of the halogen bond.
The helicity has been defined along the halogen bonding from the
I  N direction (vide infra). The supramolecular polymers were
not considered as zigzag systems because they could produce a
hole (Figure S5). The aromatic backbones of the halogen bonded
molecules were nearly perpendicular to each other. As a result,
both helices produced a rectangular cavity (Figure 1c). For both
helices, one turn consisted of two molecules and the pitch was
The crystal structure of compound 2 showed the formation of
two crescent conformational enantiomers of M and P helicity,
which was defined for the backbone from the pyridine end to the
iodine end, due to the distortion of the aromatic backbone (Figure
2a). The two conformers were alternately induced by head-to-tail
IN halogen bonding (IN distance: 2.94 Å, CIN angle:
167.9) to afford a highly malposed helical pattern (Figure 2b),
that was different from that of 1. As a result of the opposite
distortion of the M and P components in the backbones, this
halogen bonded supramolecular line formed a ꝏ-shaped helix,
which intersected at the I atoms (Figure 2c). Such a unique
arrangement of the molecular components also led to a very
oblate shape of the whole helix. As a result, both series of
conformers in the helix were highly dislocated and, in the same
series, only the i-butyl group on the pyridine ring of one molecule
overlapped with the iodine-bearing benzene ring (A, see the
structure) of another neighboring molecule. Such an oblate shape
also resulted in a very long helix pitch (22.4 Å). The tetrameric
aromatic backbone twisted to two dimeric co-planar segments,
with a torsion angle of 34.5 . No stacking was observed between
components in the same helix. Instead, the benzene (A)-amide-
benzene (B) and pyridine-amide-benzene (C) segments of one P
component of one helix stacked, through opposite orientation
(Figure 2d), with the identical counterpart of two M components of
another helix, which induced the formation of another anti-parallel
supramolecular double helix (Figure 2d). This double helix “grew”
from the two sides to afford a planar supramolecular helix array.
1
7.5 Å (Figure 1b). One P helix and one M helix stacked in an
anti-parallel manner to give rise to a supramolecular double helix
Figures 1b and 1d). The driving force came from the stacking of
(
the middle benzene and pyridine rings of the molecules located
on the inner side of the two single helices (Figure 1e). Similar
aromatic stacking also accounted for the formation of other double
or quadruple helices (vide infra), and in all the cases, the end-to-
end halogen bonding guides the linear backbones to form the
helical conformations. Another half of the molecules of both
helices stacked in the same way with counterparts of other helices
beside them, which led to the formation of supramolecular single-
component helical array in the two-dimensional space.
Figure 1. a) Conformational enantiomers of 1, b) double helix formed by
halogen bonded P (blue and light blue) and M (red and pink) helices (side view),
c) P helix (top view), d) double helix (top view), and e) stacking pattern. The
balls (I: purple, N: green, vide infra) highlighted the IN halogen bond. H atoms
were omitted for clarity. The crystals were obtained by evaporation of the
Figure 2. a) The crystal structure of the M (blue) and P (light blue) conformers
of compound 2, b) supramolecular single helix formed by halogen bonded
alternately connected M (blue) and P (light blue) conformers of 2 (side view), c)
the helix (top view), and d) supramolecular double helix formed by anti-parallel
stacking of two single helices (M: blue and pink; P: red and light blue). H atoms
were omitted for clarity.
2 2
solution in CH Cl and MeOH (3:1), as well as for the crystals of 2 and 3.
2
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anti-parallel manner, which led to the formation of another
supramolecular double helical pattern (Figures 3b). The pyridine-
amide-benzene ring (B) segments of this series of components in
the halogen bonded double helix underwent further anti-parallel
stacking with neighboring double helices to form a helix array in
the two-dimensional space (Figures 3d and 3e). Although for the
neighboring double helices, the two P or M halogen bonded single
helices did not undergo direct stacking, they did overlap
considerably (M: blue vs green; P: red vs purple, Figure 3e).
Therefore, we propose that two pairs of the double helices formed
a supramolecular quadruple-stranded helix, which was stabilized
by aromatic stacking (Figure 3d). Formally, the four halogen
bonded helices in one quadruple helix gave rise to a rhombic
structure (Figure 3c), which is reminiscent of the shape of a G-
quadruplex.
Figure 3. a) Crystal structures of the supramolecular M and P helices of
compound 3, b) supramolecular double helix formed by halogen bonded single
M (blue and light blue) and P (red and pink) helices (side view) of 3, c)
supramolecular quadruple helix of 3, highlighting a G-quadruplex-like pattern
(top view), d) quadruple helix (side view along the a axle), and e) quadruple
helix (view from the opposite direction of the middle of the a and c axles). H
atoms were omitted for clarity. c-e: side chains were omitted for clarity.
Crystals of compound 3 also revealed the formation of strong
intermolecular head-to-tail IN halogen bonding (IN distance:
Figure 4. a) P and M supramolecular single helices formed by 4 and 5, b) the
P,P and M,M supramolecular quadruple helix (left: view from the opposite
direction of the a axle, right: view from the c axle), c) the quadruple helix (view
from the b axle), d) the P,P and M,M supramolecular double helices (left: view
from the opposite direction of the a axle), and e) double helices (view from the
c axle). H atoms were omitted for clarity.
2.87 Å; CIN angle: 174.9). Although the F atoms at the 2,5-
positions of ring A (see the structure) did not form hydrogen
bonding with the neighboring amide proton, the I atom was
orientated to the side of the pyridine ring. The halogen bonding
also induced the molecules to form supramolecular P and M
helical structures (Figures 3a and 3b). For both helices, two
molecules spanned one turn. The benzene ring (A) of one
molecule and the pyridine ring of another molecule that was
halogen bonded by it had a large torsion of 51.5, which also led
to a pitch of 17.1 Å (Figure 3a). Despite possessing such a large
pitch, the two helices still produced a cavity (Figure 3c). The
adjacent P and M helices stacked with nearly all the aromatic
backbone of their component molecules on the inner side in an
Slow evaporation of the solution of compounds 4 and 5 (1:1) in
CH Cl and MeOH (5:1, v/v) gave crystals suitable for X-ray
2 2
diffraction analysis, which revealed more complicated stacking
patterns. The two molecules formed two different strong IN
halogen bonds (IN distance: 2.75 and 2.83 Å; CIN angle:
174.4 and 175.4), which induced the two molecules to form both
P and M two-component supramolecular single helices (Figure
3
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4
a). For both halogen bonded helices, four molecules (2+2)
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large pitch of 20.1 Å (Figure 4a). Intramolecular NHO hydrogen
bonding rigidified the backbone and the two pyridine N atoms
pointed to the same direction. As a result, both helices existed as
a rectangular shape as observed from the two ends (Figure 4b).
Impressively two P helices and two M helices stacked alternately
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In conclusion, we have demonstrated that halogen bonding is
an efficient noncovalent force in controlling the growth of short
arylamide foldamers to supramolecular helical structures.
Depending on the structures of the monomeric foldamers,
supramolecular single helices are able to further aggregate to
produce of more complicated double helices or even quadruple
helix. The fact that both one-component and two-component
quadruple-stranded helices can be formed demonstrates the
robustness of halogen bonding in connecting molecular
monomers into supramolecular lines. Probably due to the
existence of multiple steric i-butyl groups, all the new
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helical structures can be regulated considerably. Moreover, the
aromatic backbones can also allow for extensive modifications,
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Entry for the Table of Contents (Please choose one layout)
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Chuan-Zhi Liu, Satish Koppireddi, Hui
Wang, Dan-Wei Zhang,* Zhan-Ting Li*
Page No. – Page No.
Halogen Bonding-Directed
Supramolecular Quadruple and
Double Helices from Hydrogen
Bonded Arylamide Foldamers
Supramolecular helices: Halogen bonding “glues” short hydrogen bonded
arylamide molecules to form one- or two-component helices, which are able to
further stack to produce supramolecular quadruple and double helical structures.
5
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