Azobenzene-Based Macrocyclic Arenes: Synthesis, Crystal Structures, and Light-Controlled Molecular Encapsulation and Release

Article abstract of DOI:10.1002/anie.202015597

Azobenzene (azo)-based macrocycles are highly fascinating in supramolecular chemistry because of their light-responsiveness. In this work, a series of azo-based macrocyclic arenes 1, 2, 3, and 4, distinguished by the substituted positions of azo groups, i

Full text of DOI:10.1002/anie.202015597

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Accepted Article
Title: Azobenzene-Based Macrocyclic Arenes: Synthesis, Crystal
Structures and Light-Controlled Molecular Encapsulation and
Release
Authors: Yuezhou Liu, Hongliang Wang, Peiren Liu, Huangtianzhi Zhu,
Bingbing Shi, Xin Hong, and Feihe Huang
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10.1002/anie.202015597
Angewandte Chemie International Edition
COMMUNICATION
Azobenzene-Based Macrocyclic Arenes: Synthesis, Crystal
Structures and Light-Controlled Molecular Encapsulation and
Release
Yuezhou Liu+, Hongliang Wang+, Peiren Liu, Huangtianzhi Zhu, Bingbing Shi,* Xin Hong* and Feihe
Huang*
Abstract: Azobenzene (azo)-based macrocycles are highly
fascinating in supramolecular chemistry because of their light-
responsiveness. In this work, a series of azo-based macrocyclic
arenes 1, 2, 3 and 4 distinguished by the substituted positions of azo
groups are rationally designed and synthesized via a fragment
cyclization method. From the crystal and computed structures of 1, 2
and 3, we observe that the cavity size of these azo-macrocycles
decreases gradually upon E→Z photoisomerization. Moreover, light-
controlled host–guest complexations between azo-macrocycle 1 and
controlled molecular encapsulation and release were realized.
However, due to the lack of strategies in constructing photo-
responsive hosts which have efficient light-controlled molecular
shapes and cavity sizes and show sufficient binding affinity
changes by photoisomerization, light-controlled molecular
encapsulation and release systems relying on photo-responsive
host molecules are still rare. Therefore, it is important to develop
photo-responsive macrocycles for light-controlled molecular
encapsulation and release systems. Azobenzene (Azo), owing a
light-induced E↔Z isomerized feature, is an outstanding building
block for light responsive structures and materials.[24-27] To date,
just few examples of macrocycles containing azo units were
reported.[28-31] However, these photo-responsive macrocycles
usually need relatively complicated organic synthesis and
purification, which greatly impeded the development of photo-
responsive macrocycles. In addition, these azo-macrocycles were
constructed by para-substituted azos, macrocycles fabricated by
meta- and ortho-substituted azos have been rarely reported. Here,
we designed and synthesized a series of photo-responsive azo-
macrocycles distinguished by the substituted position of azos via
a fragment cyclization method.
guest
molecules
(7,7,8,8-tetracyanoquinodimethane,
terephthalonitrile) are successfully achieved. This work provides a
simple and effective method to prepare azo-macrocycles, and the
light-responsive molecular encapsulation systems in this work may
further advance the design and applications of novel photo-
responsive host–guest systems.
The arrival of any novel kind of macrocyclic hosts can significantly
meet the research needs of host–guest chemistry and further
enrich the field of supramolecular chemistry. During the past
decades, a great deal of macrocyclic host molecules, such as
crown ethers, cyclodextrins, calixarenes, cucurbiturils and
pillararenes were designed and reported.[1-17] The manipulation of
molecular encapsulation and release of the macrocyclic hosts by
external stimuli showed excellent performance in biomedicine,
catalysis, polymer materials, absorption and separation, and so
on.[3-8] Among various external stimuli, light responsiveness is
very fascinating due to its environmental-friendly, efficient and
non-invasive characteristics.[18] Light-controlled molecular
encapsulation and release were achieved in many instances.[19-23]
Usually, by exploiting light-responsive guest molecules, light-
Our design of these azo-macrocycles 1, 2 and 3 is shown in
Scheme 1. Three fragments, 6, 8, and 10, containing one azo unit
and two 1,4-dimethoxybenzene units were firstly prepared. Then
azo-macrocycles 1, 2 and 3 were synthesized by a fragment
cyclization method. Compounds 6 and 8 were prepared from a
Friedel-Crafts alkylation reaction between bis(hydroxyethyl)-
azobenzene and 1,4-dimethoxybenzene in the presence of
trifluoromethanesulfonic acid as the catalyst in CH3NO2, and the
reaction gave 6 and 8 in 45% and 17% yield, respectively.
Because the structure of ortho-substituted azo 10 is more
crowded than those of 6 and 8, which hindered the reaction
process, it is hard to get 10 in the same way. In order to get the
fragment 10, compound 9, containing a nitrobenzene unit and a
1,4-dimethoxybenzene unit, was prepared. Then compound 10
was obtained by the reduction reaction of 9 (43% yield). With
these three intermediates 6, 8 and 10 in hand, three azo-
macrocycles 1, 2 and 3 were synthesized via fragment cyclization
reactions by mixing the intermediate with paraformaldehyde in the
presence of BF3•(OEt2) as the catalyst in ClCH2CH2Cl.[32] The
reactions gave the targeted azo-macrocycles 1, 2 and 3 in 62%,
54% and 26% yield, respectively. Interestingly, after the
cyclization reaction of 10, an ortho-position azo-macrocycle 4 was
also obtained (7% yield). The structures of 1, 2, 3 and 4 were
Y. Liu, P. Liu, H. Zhu and Prof. Dr. F. Huang
State Key Laboratory of Chemical Engineering, Center for Chemistry of
High-Performance & Novel Materials, Department of Chemistry, Zhejiang
University, Hangzhou 310027, P. R. China
E-mail: fhuang@zju.edu.cn
H. Wang and Prof. Dr. X. Hong
Department of Chemistry, Zhejiang University, Hangzhou 310058, China
E-mail: hxchem@zju.edu.cn
Prof. Dr. B. Shi
College of Chemistry and Chemical Engineering, Northwest Normal
University, Lanzhou,730070, China.
E-Mail: bingbingshi@nwnu.edu.cn
Prof. Dr. F. Huang
Green Catalysis Center and College of Chemistry, Zhengzhou University,
Zhengzhou 450001, P. R. China.
1
characterized by H NMR, 13C NMR, MALDI-TOF-MS and X-ray
Prof. Dr. X. Hong
single crystal diffraction (Figure S1–S29).
State Key Laboratory of Clean Energy Utilization, Zhejiang University, Zheda
Road 38, Hangzhou 310027, China.
[+] These authors contributed equally to this work.
Supporting information for this article is given via a link at the end of the
document.
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10.1002/anie.202015597
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Scheme 1. Synthesis of azo-macrocycles 1, 2, 3 and 4.
irradiation at 365 nm. Orange needle-
like crystals were successfully obtained
by slow evaporation of a chloroform
solution of 1 within 2 days. X-ray
crystallographic analysis revealed that
the structure of Z,Z-1 is twisted and the
cavity becomes narrow compared with
the cavity of E,E-1 (Figure 1c and S22).
Moreover, C−H···O interactions with
H···O distances of 2.61 and 2.69 Å, a
C−H···N interaction with an H···N
distance of 2.74
Å and C–H···π
interactions with H···π-plane distances
of 2.32 and 2.56 Å are observed.
Furthermore, single crystal structure
analysis of E,E-2 shows that the length
and width of E,E-2 are about 15.79 and
7.44 Å, respectively, and the crystal
structure is stabilized by multiple C–
H···π interactions with H⋯π-plane
distances of 2.40, 2.76, 2.39, and 2.75
Figure 1. (a) Crystal structures of E,E-1, E,E-2 and E,E-3; (b) Computed structures of E,Z-1, E,Z-2 and E,Z-3;
(c) Crystal structure of Z,Z-1 and computed structures of Z,Z-2 and Z,Z-3; (d) Electrostatic potential surfaces of
E,E-1, E,E-2 and E,E-3.
Å
(Figure 1a and S24). X-ray
crystallographic analysis reveals that
High-quality orange single crystals of E,E-1, E,E-2 and E,E-3
the length of E,E-3 is 12.32 Å, and the
cavity size is much smaller than those of E,E-1 and E,E-2 (Figure
1a and S26). Moreover, a C−H···O interaction with an H···O
distance of 2.50 Å and C–H···π interactions with H⋯π-plane
distances of 2.71 and 2.78 Å are observed. We also got the
crystals of E,E,E-4 by slow evaporation in CH2Cl2 within 2 days.
X-ray crystallographic analysis reveals that E,E,E-4 has a clover-
like cavity in the solid state, and the crystal structure is stabilized
by a C−H···π interaction with an H···π-plane distance of 2.15 Å
(Figure 2 and S28). The structures of E,Z-1, E,Z-2, E,Z-3, Z,Z-2,
and Z,Z-3 were optimized with density functional theory (DFT)
calculations (Figure 1b and 1c). Based on these structural
suitable for X-ray single crystal diffraction were obtained by slow
evaporation in acetonitrile within 2 days. X-ray crystallographic
analysis revealed that E,E-1 is an oblate hexagonal macrocycle,
and the length and width of E,E-1 are 17.60 Å and 9.76 Å,
respectively (Figure 1a and S20). Besides, C−H···O interactions
with H···O distances of 2.68 and 2.66 Å, a C−H···N interaction
with an H···N distance of 2.63 Å and a C–H···π interaction with
an H···π-plane distance of 2.61 Å were observed. Moreover, a
face-to-face π-stacking interaction is noticed in the crystal
structure. The related centroid–centroid distance is 3.89 Å and the
dihedral angle is 0.59°. We tried to grow crystals of 1 upon UV
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analysis, we inferred that the cavity size of these azo-macrocycles
decreased gradually upon E→Z photoisomerization.
Figure 2. Crystal structure of E,E,E-4: (a) top view; (b) side view. Hydrogen
atoms are omitted for clarity.
The photoisomerization behaviours of 1, 2 and 3 were first
investigated by UV-Vis spectroscopy (Figure S30). Fresh CHCl3
solutions of 1, 2 and 3 were prepared. Upon irradiation with UV
light (365 nm), a decreasing peak around 334 nm corresponding
to the π−π* transition and an intensive peak around 442 nm
corresponding to the n−π* transition were observed, indicating
the E → Z photoisomerization of these azo-macrocycles.[33,34]
Moreover, reversible transformation was realized upon irradiation
with visible light (420 nm). The E↔Z photoisomerization could be
recycled for at least 5 times without obvious photo-fatigue.
Furthermore, 1H NMR experiments were carried out to study the
photoisomerization behaviours of 1, 2 and 3. For 1, the
disappearance of the signals of protons E,EH and the generation
of signals of protons Z,ZH indicated that E,E-1 was almost
completely converted into Z,Z-1 after irradiation with UV light (365
nm) (Figure S31). Furthermore, after irradiation with visible light
(420 nm), the light-induced Z → E isomerization renewedly
generated 92% of E,E-1. The photoisomerization behaviours of 2
and 3 were analogous to those of 1. Upon irradiation with UV light
(365 nm), the conversion efficiencies of E,E-2 and E,E-3 were
70% and 56%, respectively, and the percent contents of E,E-2
and E,E-3 were 72% and 82%, respectively, after irradiation with
visible light (420 nm) (Figure S32 and S33). These results
indicated that the photoisomerization behaviour of macrocycle 1
was more reversible compared with that of macrocycle 2 or 3.
DFT calculations were performed to study the thermodynamic
stabilities of the isomers of 1, 2 and 3. Consistent trend of
thermodynamic stabilities was identified for the azo-macrocycles
1, 2 and 3 (Figure S52); the E,E-isomers are the most stable. The
lowest energy conformation of Z,Z-1 was 5.3 kcal/mol higher in
free energy as compared to that of E,Z-1, and 17.6 kcal/mol
higher in free energy than that of E,E-1. The E,E-2 and E,E-3 are
also at least 5 kcal/mol more favorable than the corresponding
E,Z- and Z,Z-isomers.
Figure 3. Partial 1H NMR spectra (600 MHz, CDCl3, 298 K): (a) terephthalonitrile
(2.00 mM); (b) E,E-1⸧terephthalonitrile (2.00 mM); (c) after photoirradiation at
365 nm (30 minutes), (d) after further photoirradiation at 420 nm (30 minutes).
After the photo-responsiveness of 1, 2 and 3 was demonstrated,
light-controlled molecular encapsulation and release relying on 1,
2 and 3 was investigated. Host–guest interactions are significantly
influenced by the molecular electrostatic potential of host
molecules.[35] Therefore, the electrostatic potential surfaces of
E,E-1, E,E-2 and E,E-3 were computed (Figure 1d). The red
region showed the area with negative charge while the blue region
revealed the area with positive charge, and we could infer that
these macrocycles might have host–guest interactions with
electron-deficient guests. A typical electron-deficient molecule,
7,7,8,8-tetracyanoquinodimethane (TCNQ), was chosen as a
model guest molecule. 1H NMR experiments were carried out in
CDCl3 to study the host–guest complexation (Figure S34–S36).
After mixing TCNQ with E,E-1, E,E-2 or E,E-3, the signal of
protons on TCNQ shifted upfield obviously, indicating the
formation of the host–guest complex. Furthermore, 1H NMR
titrations were carried out to evaluate the stoichiometry and
association constant Ka (Figure S44–S49). By a mole ratio plot,
1 : 1 stoichiometry was obtained for these complexations. The Ka
values were estimated to be 487 ± 26 M−1, 236 ± 9 M−1 and 46 ±
5 M−1 for E,E-1⸧TCNQ, E,E-2⸧TCNQ and E,E-3⸧TCNQ,
respectively. The host–guest complex of E,E-1⸧TCNQ was also
optimized by DFT calculations (Figure S56). Moreover, only E,E-
1 showed the ability to capture terephthalonitrile into the cavity.
From the 1H NMR results, after mixing terephthalonitrile with E,E-
2 or E,E-3, no obvious chemical shift change was observed
(Figure S38 and S39), indicating that there was no or very weak
complexation between them in CDCl3. Contrastively, distinct
chemical shift changes of protons on E,E-1 and terephthalonitrile
were observed after adding 1.00 equiv. of terephthalonitrile into a
solution of E,E-1 (Figure 3a, 3b and S37). The peaks related to
E,EHa on E,E-1 and H1 on terephthalonitrile shifted upfield. The Ka
value was estimated to be 34.1
±
4.4 M−1 for E,E-
1⸧terephthalonitrile in a 1 : 1 complexation mode. As mentioned
above, the photoisomerization behaviour of macrocycle 1 was
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In conclusion, photo-responsive azo-based macrocyclic arenes
1, 2 and 3 distinguished by the substituted positions of azo groups
were prepared via fragment cyclization reactions. Furthermore,
an ortho-position azo-macrocycle 4 was also obtained. Excitingly,
we not only got the crystal structures of E,E-1, E,E-2, E,E-3 and
E,E,E-4, but also obtained the crystal structure of Z,Z-1 upon UV
irradiation at 365 nm. In addition, azo-macrocycle E,E-1 can form
host–guest complexes with electron-deficient molecules, TCNQ
and terephthalonitrile. The encapsulation and release of guest
molecules can be controlled by photo irradiations. This work
provided a novel, straightforward and high-efficiency approach to
fabricate photo-responsive azo-macrocycles. Based on the
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responsiveness of these azo-macrocycles, we believe that they
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This work was supported by the National Natural Science
Foundation of China (22035006, 21702182 and 21873081),
Fundamental Research Funds for the Central Universities
(2020XZZX002-02), the State Key Laboratory of Clean Energy
Utilization (ZJUCEU2020007), China Postdoctoral Science
Foundation (2019M652056) and Zhejiang Provincial Natural
Science Foundation of China (LD21B020001). Calculations were
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Keywords: macrocycles • supramolecular chemistry • light-
responsiveness • host–guest systems • photochemistry
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TOC
A
series of azobenzene (azo)-macrocycles 1, 2 and 3 distinguished by the substituted positions of azo are synthesized
A series of azobenzene-based macrocyclic arenes 1, 2 and 3 are synthesized, and light-
controlled molecular encapsulation and release are realized based on macrocycle 1.
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