Hydrogen-bonding induced construction of a multiple double-helical system via a macrocycle-containing propargylamine backbone

Article abstract of DOI:10.1080/10610278.2014.962027

Two macrocyclic compounds containing propargylamine backbone have been synthesised via Mannich three-component reaction. The macrocycle 3a shows the intramolecular self-folding conformation. The macrocycle 3b self-assembles via multiple weak interactions

Full text of DOI:10.1080/10610278.2014.962027

Supramolecular Chemistry, 2015
Vol. 27, Nos. 5–6, 420–424, http://dx.doi.org/10.1080/10610278.2014.962027
Hydrogen-bonding induced construction of a multiple double-helical system via a
macrocycle-containing propargylamine backbone
Yu Sun and Wu An-Xin*
Central China Normal University, Wuhan, P.R. China
(
Received 31 May 2014; accepted 1 September 2014)
Two macrocyclic compounds containing propargylamine backbone have been synthesised via Mannich three-component
reaction. The macrocycle 3a shows the intramolecular self-folding conformation. The macrocycle 3b self-assembles via
multiple weak interactions to form a multiple double-helical system, which shows the alternate helical handedness.
Keywords: hydrogen bonds; foldamer; helix; macrocycle; propargylamine
Introduction
hydrogen-bonding and weak interaction, has been rarely
reported.
Helicity is the universal existence in the living world (1).
A wide range of helical structures can be observed in
nature for functions such as essential element of life,
information storage, asymmetric catalysis and formation
of ion channels (2). Regardless of the artists or chemists,
the pursuit of aesthetics is endless (3). In this sense, as a
very important topological motif, helicity has caught a lot
of attention for its intriguing structures (4). Generally, the
formation of most helices has been realised by means of
covalent (5), coordinate (6) and metal–metal dative bonds
Herein, we report a new covalent macrocycle that has
been used as a linker to construct a multiple double-helix
system by CZH· · ·N hydrogen bonds and intermolecular
weak interactions of CZH· · ·p, which makes the control
of relative orientation and helical handedness come true.
Owing to the opposite handedness of each helical unit, the
multiple double-helical system shows a left- and right-
alternating phenomenon.
(
7). Only a few constructions of helical and multiple
Results and discussion
helical structures are aggregated via hydrogen bonding or
p–p stacking (8). Hydrogen bonds have gradually
occupied a dominating position for the construction of
infinite single, double, triple and quintuple helical
assemblies because of its strength, directionality, reversi-
bility and selectivity in achieving the helicity (9). Thus, the
search for new structural motifs in helical architectures
formed by non-covalent interaction has been a necessary
research area to date (10).
In the previous research from our laboratory, the formation
of an unprecedented metal-free triple helix has been
reported, which is driven by weak CZH· · ·p and
CZH· · ·O interactions based on a unique supramolecular
synthon macrocycle (15). Being encouraged by this
wonderful result, further examinations of the higher-order
formation of helical systems have been carried out. Two
macrocyclic compounds containing the propargylamine
backbone were synthesised by Mannich three-component
reaction (Scheme 1).
On the other hand, although the basic features of
discrete helices or low-dimensional helices are now well
established, the design and control of the assembly of the
helical unit into a multiple helical system still remain a
challenge (11). Ivan Huc and co-workers have reported a
helix–linker–helix supramolecular structure composed of
two helices connected by a linker, such as metal complexes
as dynamic connection elements (12), binaphthyldiamine
as the turn to connect two helical secondary structures (13)
and a short connecting spacer placed in the middle of the
sequences of the two helical segments (14). To the best of
our knowledge, the macrocycle serving as a linker, which
controls the relative orientation and handedness of two
neighbouring helices, as well as self-assembles via
A crystal of macrocycle 3a (C H N O ) was
3
6 40 4 4
obtained from a CHCl /CH OH diffusion. Single-crystal
3
3
data were recorded on a Smart Apex CCD area detector
at 298(2) K. The crystal structure was solved in the
triclinic P 2 1 space group and an interesting structure
of foldamer has been found unexpectedly. Four pairs
of intramolecular complementary CZH· · ·p interactions
(C12ZH12A· · ·Centroid A, d ¼ 2.95 A˚ , u ¼ 1098;
C13ZH13B· · ·Centroid A, d ¼ 2.76 A˚ , u ¼ 1118;
C14ZH14B· · ·Centroid A, d ¼ 2.88 A˚ , u ¼ 1118; C11–
H11A· · ·Centroid A, d ¼ 2.92 A˚ , u ¼ 1108) (Figure 1(a))
exist from the methylene groups of piperazine to
*Corresponding author. Email: chwuax@mail.ccnu.edu.cn
q 2014 Taylor & Francis

Supramolecular Chemistry
421
(
a)
OH
OH
O
O
Br
2
Cs CO3
DMF(dry)
rt
1
2
N
N
N
N
O
O
O
O
O
O
CuCl
dioxane
0°C
HN
N H
H
H
O
9
2
3
(
b)
N
N
N
N
N
N
O
O
O
O
O
O
O
O
N
N
3a
3b
Scheme 1. (Colour online) Synthesis route of macrocycles 3a and 3b. (a) Reaction conditions of terminal diyne 2: pyrocatechol (or
naphthalene-2,3-diol) 1 (1.0 mmol), 3-bromoprop-1-yne (2.6 mmol), Cs CO (2.4 mmol), dry DMF (3 mL), room temperature, 5 h. (b)
2
3
Reaction conditions of macrocyclic compound 3: terminal diyne 2 (1.0 mmol), secondary diamine (1.0 mmol), formaldehyde (2.0 mmol)
and CuCl (1.0 mmol), dioxane (30 mL), 908C, 2 h.
ZCuCZ groups, and
a
CZH· · ·p interaction
˚
(
(
C13ZH13B· · ·Centroid A, d ¼ 2.99 A, u ¼ 1508)
Figure 1(a)) exists from the methylene groups of
piperazine to the aromatic rings, which drives the
occurrence of intramolecular self-folding. In the internal
monomer molecule, the dihedral defined by the plane
(C9/C10/C15/C16) and the plane (C10/C15/N1/N2) is
about 68.638 (Figure S1) and the dihedral defined by the
plane (C8/C9/C16/C17) and the plane (C1/C6/O1/O2) is
about 74.478 (Figure S1). Meanwhile, multiple inter-
molecular weak interactions such as CZH· · ·O hydrogen
˚
bonds
(C7ZH7B· · ·O1,
d ¼ 2.53 A,
u ¼ 1648;
˚
C7ZH7B· · ·O2, d ¼ 2.54 A, u ¼ 1328) from methylene
groups to O atoms, and CZH· · ·p interactions
˚
(
C15ZH15B· · ·Centroid A, d ¼ 2.83 A, u ¼ 1458) from
methylene groups to ZCuCZ groups, also appear to
play an important role in stabilising the structure of
the foldamer and in forming a network structure
(
(
Figure 1(b)). In comparison with the metal cation–p
16) and anion–p (17) interactions that have been used
to achieve the structure of foldamer, intramolecular weak
interactions provide an effective way to form supramo-
lecular foldamers.
We were also fortunate enough to get a crystal of
macrocycle 3b (C H N O ) from a CH Cl/CH OH
diffusion. Single-crystal data were recorded on a Smart
Apex CCD area detector at 296(2) K. The crystal structure
Figure 1. (Colour online) (a) Crystal structure of foldamer
formed through CZH· · ·p interactions. (b) View of packing
of 3a. Intermolecular interactions are shown as dashed lines.
H atoms have been omitted for clarity.
4
4
44
4
4
3
3

4
22
Y. Sun and W. An-Xin
illustrated that the helical chain was thus paired under
the direction of weak intermolecular CZH· · ·p inter-
˚
actions (C11ZH11A· · ·Centroid C, d ¼ 3.09 A,
u ¼ 159.178) (red dashed lines) (Figure S2) from
methylene groups to the naphthalene rings, resulting in
homochirality double-strand helices with the same screw
˚
axis (Figure 3(b)). The helical diameter is 1.66 A
˚
(Figure S3) and the helical pitch is 11.03 A (Figure S4).
We noted that the left-handed chirality of the homochir-
ality double-strand helical chains and its orientation are
transferred oppositely to the neighbouring parallel one
through the macrocycle bridge, leading to the formation of
a 2D multiple double helix (Figure 3(e)).
Because the molecule possesses no stereogenic centre,
each of its helices may exhibit left- or right-helicity, and the
whole molecule may exist in two distinct forms (18). Here,
two propargylamine backbones located in the symmetric
position of the macrocycle linker can constitute a double-
helical chain with adjacent ones respectively. It provides the
possibility for the formation of the multiple double-helical
system (Figure 4(a)). Further analysis showed that six
double-helix units are connected to form a 3D multiple
double-helical system by the macrocycle bridge, with the
Figure 2. (Colour online) (a) Three adjacent macrocycles
viewed down from the c-axis. (b) The structure of a 1D left-
handed helical chain formed by CZH· · ·N hydrogen bonds and
CZH· · ·p interactions. (c) Pictogram of the 1D left-handed
helical chain. (d) The macrocycle acts as a linker to connect two
helical chains. (e) The left-handed chirality transferred to the
right-handed chains through the macrocycle linker. (f) Pictogram
of 2D multi-helix. H atoms have been omitted for clarity.
was solved in the Rhombohedral R-3 space group. Three
adjacent macrocycles provide the same functional group of
propargylamine (Figure 2(a)). It makes the molecule
arrange as a 1D left-handed helical chain via intermole-
cular C–H· · ·N hydrogen bonds (C22ZH22A· · ·N2,
˚
d ¼ 2.57 A, u ¼ 1458) (green dashed lines) (Figure 2(b)).
Meanwhile, the weak interactions of CZH· · ·p
˚
(
C19ZH19B· · ·Centroid B, d ¼ 3.00 A, u ¼ 1368) (blue
dashed lines) also contribute to building the helical chain
and stabilising the framework of molecule. Moreover, the
other functional group of propargylamine located in the
symmetric position of the macrocycle can also get together
with other two neighbouring ones (Figure 2(d)) to form
another chirality transferred 1D right-handed helical chain
(
Figure 2(e)) via both intermolecular CZH· · ·N hydrogen
bonds and CZH· · ·p interactions. Owing to the control of
the macrocycle linker in a parallel way, the left-handed
chirality and orientation of the original formed chain are
inverted and transferred to the neighbouring parallel
helical chains through a macrocycle bridge, leading to a
Figure 3. (a) Three adjacent macrocycles viewed down from
the c-axis. (b) The structure of a 1D left-handed double helix
formed by intermolecular CZH· · ·p interactions. (c) Pictogram
of the 1D left-handed double helix. (d) The macrocycle acts as a
linker to connect two double helices. (e) The left-handed chirality
transferred to the right-handed chirality through the macrocycle
linker. (f) Pictogram of 2D multiple double helix. H atoms and
intermolecular CZH· · ·p interactions have been omitted for
clarity.
2
D multi-helix (Figure 2(e)).
As the naphthalene ring is known as a p acceptor, it
was supposed that it could provide potential sites to stack
to form more complex helical architectures via CZH· · ·p
interaction. More interestingly, a detailed analysis

Supramolecular Chemistry
423
ethyl acetate and washed three times with brine, to
completely remove DMF. After workup, the solvent was
removed under reduced pressure. The solid residue was
purified by flash chromatography [SiO , petroleum ether/
2
ethyl acetate (30:1)] to give the product of terminal diyne
(transparent liquid, yield 93%).
Naphthalene-2,3-diol (1.0 mmol) was dissolved in dry
DMF (3 mL) and then Cs CO (2.4 mmol) was added.
2
3
After 15 min, 3-bromoprop-1-yne (2.6 mmol) was added at
room temperature. The reaction was monitored by TLC,
and after completion (5 h), the mixture was diluted with
ethyl acetate and washed three times with brine, to
completely remove DMF. After workup, the solvent was
removed under reduced pressure. The solid residue was
purified by flash chromatography [SiO , petroleum ether/
2
ethyl acetate (30:1)] to give the product of terminal diyne
(white solid, yield 88%).
Figure 4. (Colour online) (a) Six double-helix units are
connected to form a multiple double-helix system viewed down
from the c-axis. (b) The handed chirality of each double helix
presents left and right alternates. (c) Pictogram of 3D multiple
double-helix system. H atoms and intermolecular CZH· · ·p
interactions have been omitted for clarity.
Preparation of macrocyclic compound 3a
Terminal diyne (1.0 mmol), secondary diamine
(
1.0 mmol), formaldehyde (2.0 mmol) and CuCl
handed chirality of each double helix presenting left and
right alternates (Figure 4(b)).
(1.0 mmol) in dioxane (30 mL) were heated at 908C for
2 h (15). After workup, the solvent was removed under
reduced pressure. The solid residue was purified by flash
chromatography [SiO , CHCl /CH OH (80:1)] to give
2
3
3
Conclusion
the product 3a (yield 29%) as a white solid. M.p.:
2
173.2–177.88C. IR (KBr, cm ): 3437, 3066, 2941,
1
Macrocyclic compounds 3a (C H N O ) and 3b
3
6
40
4
4
(
successfully synthesised by the Mannich three-component
C H N O ) with propargylamine backbone were
2909, 2822, 2778, 1596, 1500, 1454, 1238, 1126,
2
4
4
44
4
4
1
1
746 cm . H NMR (600 MHz, CDCl
4H), 6.94 (m, 4H), 4.78 (s, 8H), 3.28 (s, 8H), 2.53 (s,
): d ¼ 7.04 (m,
3
reaction. The crystal structure of macrocycle 3a
C H N O ) shows a self-folding behaviour controlled
1
3
(
16H). C NMR (150 MHz, CDCl
18.79, 85.49, 80.08, 57.75, 49.45, 46.27. HR-MS
3
): d ¼ 147.92, 122.66,
3
6 40 4 4
1
by intramolecular CZH· · ·p interactions and stabilised via
intermolecular CZH· · ·O hydrogen bonds and CZH· · ·p
interactions. Moreover, the crystal packing of macrocycle
þ
(
APCI): m/z [M þ H] calcd for C36H41N4O4:
93.3122; found: 593.3122.
5
3
b (C H N O ) shows the transference of chirality
44 44 4 4
between the helical chains, which is dependent on the
interchain connections. Due to the macrocycle linker, the
handed chirality and relative orientation of the originally
formed helical chains being inverted and transferred to the
neighbouring one. Furthermore, six pairs of double-helix
units are connected to form a 3D multiple double-helical
system with alternating handedness. Further explorations
of related helical structures are currently underway in our
laboratory.
Preparation of macrocyclic compound 3b
Terminal diyne (1.0 mmol), secondary diamine
(
(
1.0 mmol), formaldehyde (2.0 mmol) and CuCl
1.0 mmol) in dioxane (30 mL) were heated at 908C for
2
h. After workup (monitored by TLC), the solvent was
removed under reduced pressure. The solid residue was
purified by flash chromatography [SiO , CHCl /CH OH
2
3
3
(80:1)] to give the product 3b (yield 33%) as a yellow
solid. M.p.: 118.1–127.38C. IR (KBr, cm ): 3424,
2
1
3
1
7
055, 2931, 2905, 2816, 1627, 1600, 1509, 1484, 1455,
2
Experimental section
1
1
256, 1130, 744 cm
.65 (m, 4H), 7.37 (m, 4H), 7.28 (s, 4H), 4.91 (s, 8H),
.
H NMR (600 MHz, CDCl3):
Preparation of terminal diyne
1
3
Pyrocatechol (1.0 mmol) was dissolved in dry DMF
(
3.21 (s, 8H), 2.36 (s, 16H). C NMR (150 MHz,
CDCl ): d ¼ 147.26, 129.19, 126.47, 124.72, 109.73,
3 mL) and then Cs CO (2.4 mmol) was added. After
2
3
3
15 min, 3-bromoprop-1-yne (2.6 mmol) was added at room
temperature (19). The reaction was monitored by TLC,
and after completion (5 h), the mixture was diluted with
83.77, 79.62, 56.83, 51.94, 47.05. HR-MS (APCI): m/z
þ
[M þ H] calcd for C44H45N4O4: 693.3435; found:
693.3429.

4
24
Y. Sun and W. An-Xin
Supplementary data
Piguet, C. Inorg. Chem. 2004, 43, 1840–1849. (c) Cui, Y.;
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1
13
General experimental procedure, H and C spectra, X-
ray crystallographic files and other related figures for
compounds 3a and 3b can be found here: http://dx.doi.
org/10.1080/10610278.2014.962027
6
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