Covalent Organic Framework for Improving Near-Infrared Light Induced Fluorescence Imaging through Two-Photon Induction

Article abstract of DOI:10.1002/anie.201912594

Fluorescent materials exhibiting two-photon induction (TPI) are used for nonlinear optics, bioimaging, and phototherapy. Polymerizations of molecular chromophores to form π-conjugated structures were hindered by the lack of long-range ordering in the stru

Full text of DOI:10.1002/anie.201912594

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Accepted Article
Title: Slipped Structure of Covalent Organic Framework Facilitates
Two-Photon Adsorption for Improving Near-Infrared Excited
Fluorescence Imaging
Authors: Jin-Yue Zeng, Xiao-Shuang Wang, Bo-Ru Xie, Min-Jie Li, and
Xian-Zheng Zhang
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201912594
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10.1002/anie.201912594
Angewandte Chemie International Edition
RESEARCH ARTICLE
Slipped Structure of Covalent Organic Framework Facilitates
Two-Photon Adsorption for Improving Near-Infrared Excited
Fluorescence Imaging
Jin-Yue Zeng,[a] Xiao-Shuang Wang,[a] Bo-Ru Xie,[a] Min-Jie Li,[a] and Xian-Zheng Zhang[a,b]
*
Abstract: Fluorescent materials exhibiting the characteristics of
strong two-photon absorption (TPA) are extensively used for
nonlinear optics, bio-imaging and phototherapy. One practical
approach to obtain fluorescent materials with high TPA performance
is to polymerize molecular chromophores to form π-conjugated
structure. This leads to the increase in TPA cross-section per
chromophore, however, efforts to towards this direction was capped
by the lack of long-range ordering in the structure and the strong π-π
stacking between the chromophores. Here, we reported the rational
design of benzothiadiazole-based covalent organic framework (COF)
for promoting TPA performance and obtaining the efficient two-
photon excited fluorescence. Structure characterizations and
spectroscopic studies revealed that the enhancement in TPA
performance was attributed to the donor-π-acceptor-π-donor (D-π-
A-π-D) configuration of the chromophore, long-range order, and
large π-conjugation domain of COF crystals. The structural slipping
in TPA-COF not only attenuates the π-π stacking interaction
between the layers, but more importantly, overcomes the
aggregation-caused emission quenching of the chromophores for
improving near-infrared two-photon excited fluorescence imaging.
the configuration inversions of the linkers in the lattices and the
enforced π-conjugation that ensures the extended delocalization
of π-electrons, were much less explored.[5] These are critical,
however, for their electrical, magnetic and optical properties.
Organic conjugated chromophores possessing a large two-
photon absorption (TPA) cross-section are of interest for many
practical applications, such as nonlinear optics, 3D fluorescence
imaging and phototherapy.[6] The two-photon excitation with
near-infrared (NIR) light provides a better definition of less
photo-damage, the focal spot and resolution, and deeper
penetration in biological tissues compared with general one-
photon excitation upon UV and visible light (Figure 1A and 1B).[7]
To facilitate these applications, the development and design of
fluorescent materials with efficient TPA performance are
essential.[8] The TPA performance of fluorescent materials is
generally determined by their TPA cross-section, which is
influenced by the molecule conformation, the transition dipole
moment of molecule and π-conjugation domain.[9] Previous
studies indicated that the TPA cross-section can be improved in
amorphous polymer by enlarging the π-conjugated domain.[10]
Meanwhile, the increase of TPA cross-section was also found in
recent study in metal organic frameworks (MOFs) by
incorporating the chromophores into three-dimensional crystal
lattices.[11] These approaches led to the enhancement in TPA
cross-section per chromophore, however, efforts to towards this
direction was limited by π-π stacking between the chromophores
and the lack of long-range ordering in the structure.[12]
Introduction
Integrating functional molecules into conjugated crystalline
structures represents a fast-developing branch of material
science in the past few decades.[1] Covalent organic frameworks
(COFs), constructed by linking organic molecules through
covalent bond, are a class of emerging crystalline porous
polymer, which exhibit the atomically precise incorporation of
organic units into extensible structures with periodic frameworks
and ordered nanopores.[2] Indeed, COFs provide confined
molecular spaces for the interaction of photons, excitons,
electrons, holes and guest molecules, thereby displaying unique
molecular and crystalline features.[3] The molecular features of
these materials allows for the design and tailoring of their pore
properties and functionality, providing specific interaction with
guest molecules, thus leads to excellent performance in
separation, catalysis, molecular recognition and drug delivery.[4]
On the other hand, the crystalline features, involving the long-
range ordering between molecular building blocks that restricted
Here, we designed a benzothiadiazole-based COF with
slipped structure to promote TPA performance by using donor-
π-acceptor-π-donor
(D-π-A-π-D)
configuration
of
the
chromophores as building blocks, and to achieve the efficient
TPA performance for NIR-excited fluorescent materials (Figure
1C and 1D). The promotion of TPA performance was attributed
to the following several factors: a) D-π-A-π-D configuration of
the chromophores to enhance polarization of the charge
distribution.[13] b) Large π-conjugation domain to ensure effective
π-delocalization with strong extended intramolecular charge
transfer.[14a] c) Restriction of intramolecular bond rotation to
[14b]
block the non-radiative energy decay pathway.
d) Regular
intervals of the TPA chromophore in slipped frameworks to avoid
unwanted aggregation and concentration quenching.[15] Because
of exploiting the unique nature of COF, the long-range crystal
domain and eclipsed π-π stacking structure will be greatly
improved with enforced coplanarity conformation which will lead
to high dipole value and large TPA cross-section value.[14a] As a
proof-of-concept, the benzothiadiazole-based COF with high
TPA activity was used as enhanced fluorescent material for two-
photon excited fluorescence imaging in vitro and in vivo (Figure
1E).
[a]
[b]
Dr. J.-Y. Zeng, X.-S. Wang, B.-R. Xie, M.-J. Li, Prof. Dr. X.-Z. Zhang
Key Laboratory of Biomedical Polymers of Ministry of Education &
Department of Chemistry, Wuhan University
Wuhan 430072, China
E-mail: xz-zhang@whu.edu.cn
Prof. Dr. X.-Z. Zhang
The Institute for Advanced Studies, Wuhan University
Wuhan 430072, China
Supporting information for this article is given via a link at the end of
the document.
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10.1002/anie.201912594
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RESEARCH ARTICLE
Figure 1. (A) Schematic illustration of one-photon, two-photon excitation and the advantages of two-photon excitation. (B) Schematic illustration of the mechanism
of two-photon excited fluorescence emission. (C) The choice of building block with π-acceptor-π-donor (D-π-A-π-D) chromophores. (D) Illustration of the
molecular feature and the crystalline feature of COFs. (E) Schematic illustration of TPA-COF facilitates near-infrared excited fluorescence emission (left, the
mechanism of two-photon excited fluorescence emission; right, the schematic energy level diagram of two-photon excited fluorescence emission).
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RESEARCH ARTICLE
Figure 2. (A) Schematic illustrating the synthesis of TPA-COF. (B) The restricted conformation dynamics in the crystal lattice. (C) The disorder structure induced
weak TPA efficiency. (D) Illustration of the long-range ordering coherent domain and the cooperative enhancement of transition dipole in TPA-COF led to strong
TPA efficiency.
belonging to the ligands at 190.6 ppm disappeared completely in
the CP/MAS 13C NMR spectrum, and a new peak at 158.7 ppm
emerged, indicating the quantitative formation of imine linkages
(Figure S2 and S3). The porosity of TPA-COF was investigated
by measuring N2 adsorption-desorption at 77 K exhibited a rapid
uptake at a low pressure of P/P0 < 0.1, followed by a sharp step
between P/P0 = 0.1. The Brunauer-Emmett-Teller (BET) surface
areas of TPA-COF is found to be 1030 m2 g-1 indicating that
TPA-COF has good to porosity (Figure S4). The morphology of
TPA-COF was examined by both scanning electron microscopy
(SEM) and transmission electron microscopy (TEM), where the
COF exhibited uniform layered structures with ordered shapes
(Figure 3A and 3B). The elemental mapping of C, N, O and S in
a single TPA-COF showed geometrical and compositional
distributions (Figure 3E). These results indicated that a porous
polymer was constructed by linking benzothiadiazole-based
aldehyde with aniline building blocks through covalent bond.
Results and Discussion
The typical synthesis of COF with TPA (TPA-COF) was
achieved by solvothermal reaction of benzothiadiazole-based
aldehyde molecular chromophores with aniline building blocks,
where the reversibility of the imine linkage guaranteed the
formation of COF with high crystallinity, thus led to excellent
long-range ordering of the molecular chromophores (Figure 2A-
2D). A series of spectroscopic experiments were performed to
characterize the structure of TPA-COF. The Fourier transform
infrared (FT-IR) spectrum of TPA-COF clearly show the
characteristic telescopic vibration of imine bond (ν C=N) at 1612
cm-1, suggesting the formation of the imine linkage (Figure S1).
The quantitative conversion of the aldehyde was further
confirmed by the cross-polarization magic-angle-spinning 13C
solid-state nuclear magnetic resonance (CP/MAS 13C NMR)
spectrum. After constructing to COF, the aldehyde carbon peak
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Figure 3. (A) SEM image of TPA-COF. (B) TEM image of TPA-COF. (C) Scanning TEM (STEM) image of TPA-COF under integrated differential phase contrast
(iDPC) method. (D) Electron diffraction pattern of TPA-COF. (E) HAADF-STEM image and the corresponding STEM-EDS elemental mapping images of TPA-COF,
scale bar = 50 nm (E1, merge; E2, C; E3, O; E4, N; E5, S). (F) Inverse FFT of C, which matched well with the structure solved by Pawley refinement. (G) Inverse
voids changes of F. (H) Electron diffraction fringe of TPA-COF. (I) Small angle X-ray scattering (SAXS) data of TPA-COF. (J) Simultaneous Pawley refinements of
experimental synchrotron data of TPA-COF, where red circles are experimental data, black line is calculated data, green line is the difference and purple bars
Bragg positions (λ = 1.2398 Å).
The crystallinity of TPA-COF was reflected in the sharp
peaks in the powder X-ray diffraction (PXRD) patterns collected
using both lab-based and synchrotron X-ray source. To
determine the crystal structure of TPA-COF, the model was built
on the basis of the possible linkages between aldehyde
chromophores and aniline building blocks and with different
interlayer stacking for the layered structures. Comparison
between the experimental PXRD pattern with the calculated
from simulated structure showed excellent match in both peak
positions and intensities for the layered model with eclipsed
interlayer stacking (Figure S5). The PXRD pattern was refined
against simulated COF structure by Pawley refinement, where
crystal lattice in P1 space group, a = 46.889 Å, b = 34.518 Å, c =
7.937 Å and α = 94.51°, β = 89.46°, γ = 90°, was observed with
acceptable residues (Figure 3J). The accurate distance between
layers along the c axis was determined from the 001 peak at 2θ
= 22.0° in the PXRD pattern. In addition, small angle X-ray
scattering (SAXS) patterns were measured for these samples to
provide accurate positions and intensities for low angle peaks
(100, 110, 120, 200 and 310, etc.) (Figure 3H and 3I). The
refinement for both the PXRD and SAXS patterns yielded low
residues. To confirm the correct choice of space group for TPA-
COF in the structure refinement, electron diffraction (ED) was
taken on TPA-COF crystals using TEM. The ED pattern along
the zone axis of [001] direction revealed the high crystallinity of
TPA-COF and determined γ angle for the crystal lattice, which
was in good accordance with that obtained from PXRD
refinement (Figure 3D). Furthermore, the hexagonal pores and
the close packing between the layers of TPA-COF was
visualized by high resolution TEM (HR-TEM) images and
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scanning TEM (STEM) images, which matched well from the
structure solved by PXRD (Figure 3C). Here, we used integrated
differential phase contrast (iDPC) method on the STEM model,
where the intensity of the signal in the image reflects the phase
transition function of TPA-COF (Figure 3F). This allowed us to
achieve a resolution of 2.3 Å and directly observe the pores of
TPA-COF, with a size of 28.2 Å along [100] direction, which was
also consistent with the PXRD results (Figure 3G). These results
reveal that TPA-COF exhibits good crystallinity and the
structural slipping of the chromophores, which is important to
obtain strong fluorescence emission.[16]
Figure 4. (A) The contours of voids in TPA-COF. (B) The contours and planes of voids in TPA-COF. (C) The surface of voids in TPA-COF. (D) Bandgap of
amorphous polymer and TPA-COF (Left, simulated bandgap of ligand and π-extended ligand). (E) TPA cross-section value of the ligand and the corresponding
amorphous polymer and TPA-COF. (F) UV-vis diffuse reflectance spectrum and two-photon excited emission of TPA-COF. (G) Molecular orbital amplitude plots of
HOMO and LUMO of the ligand and π-extended ligand calculated at the B3LYP/6-31G (d, p) basis set.
The two-photon action across-section was determined by
using the femtosecond fluorescence measurement technique
(Figure 4F). The TPA-COF was well dispersed in water with the
modification of PF-127 by ultrasound and the two-photon
induced fluorescence intensity was measured in the range from
760 to 860 nm by using Rhodamine B in methanol at a
concentration of 1x10-5 M as the reference (Figure 4E). Notably,
ligand displays a TPA cross-section of 190 GM (Goeppert-Mayer
unit), whereas TPA-COF show an enhanced value of 5500 GM
(Rhodamine B, TPA = 70 GM, excited at 780 nm). Furthermore,
TPA performance of TPA-COF was promoted drastically as the
coherent domain increased. The TPA cross-section values of
TPA-COF per chromophore had already doubled that of
amorphous sample (1100 GM). This value rivaled that of the
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state-of-the-art molecule-based TPA materials, demonstrating
the power of coherent domain in TPA performance. The
extension of π-conjugation is often blocked to form amorphous
polymers for their polymerization reactions are irreversible and
lack of an in situ structural self-healing process. To better
understand two-photon excitation transitions within π-
conjugation structures, we carried out density functional theory
(DFT) calculations for the ligand and the corresponding π-
conjugation structure. The molecular orbital density of the
HOMO is primarily located on the π-conjugation moiety and the
central benzothiadiazole ring, while the LUMO level is mainly
Figure S13, when TPA-COF were treated with PBS solution (50
mM) for 12 and 24 h, PXRD patterns have no obvious change.
This result indicates that TPA-COF exhibited good structure
stability. To assess the biosafety of the TPA-COF, the
established methyl thiazolyl tetrazolium (MTT) assay was carried
out on the normal (3T3) and cancer (4T1) cells line in the dark or
with 808 nm laser irradiation (Figure 5C and 5D). Moreover,
TPA-COF showed good biocompatibility with over 90% cell
viability when incubated with cells alone. The decrease in cell
viability in Figure 5C and 5D could be attributed to weak photo-
thermal effect of TPA-COF under laser irradiation (Figure S14
and S15). Notably, the cells could well survive when treated with
250 μg/mL of TPA-COF upon 808 nm laser irradiation.
localized
on
the
acceptor
framework,
suggesting
a significant decrease in the bandgap for the π-extended
structure (Figure 4G).
Given the crystalline structure of TPA-COF, we inferred that
the underlying mechanism for the promotion in TPA
performance could be attributed to the restriction of the
conformation dynamics, the formation of π-conjugation domain
and long-range order in TPA-COF. The voids and surface of
TPA-COF were calculated by Olex 2, indicating the structural
slipping in the crystal structure (Figure 4A-4C). The layered
eclipsed stacking configuration imposed by the triarylamine unit
in TPA-COF restricted the conformation dynamics. Here, this not
only increased the crystallinity of TPA-COF, but also reduced
the unwanted the non-radiative energy decay during the TPA
process. Furthermore, the impact of π-conjugation domain was
further investigated by spectroscopic studies. The band gap was
measured by UV-vis diffuse reflectance spectroscopic (DRS),
while the valence band was given by ultraviolet photoelectron
spectroscopic (UPS) collected using XPS instrument, therefore
revealing the accurate band structure of TPA-COF (Figure 4F
and S6). In comparison to the corresponding molecular building
blocks, TPA-COF exhibited lower fluorescence lifetime, excellent
photo-stability and wide range of excitation (Figure S6-S10).
This combined with the red shift in the UV-vis absorption
spectrum confirmed the cooperation between chromophores
across the entire COF crystals (Figure 5B). The interaction
between chromophores at different layers along c axis of the
crystal lattice was reflected in the chemical shift of the carbon on
the triarylamine motif after the formation of COF, where the
rotation freedom of the aryl group was restricted. The
differences in π-conjugation domain were further reflected in
their optical properties. As the coherent domain increased, the
one-photon fluorescence intensity of TPA-COF enhanced
drastically, while the band gap decreased from 2.52, 2.14 to
2.03 eV for the ligand, amorphous polymer and long-range
crystal, respectively (Figure 4D, S11 and S12).
Figure 5. (A) Particle size and zeta potential of TPA-COF. (B) UV-vis and
fluorescence spectrum of TPA-COF. (C) The cytotoxicity of TPA-COF against
normal cells. (D) The cytotoxicity of TPA-COF against cancer cells. (E) Two-
photon fluorescence imaging of TPA-COF against 4T1 cells. (F) One-photon
fluorescence imaging of TPA-COF against 4T1 cells. Scale bar, 50 μm.
The intracellular distribution and uptake of TPA-COF were
confirmed by two-photon confocal laser scanning microscopy
(CLSM) in 4T1 cell line. It was found that obvious yellow
fluorescent signal from the endocytosis of TPA-COF was
observed through CLSM upon two-photon excitation with an 810
nm laser, indicating that TPA-COF exhibited efficient two-photon
fluorescence and could be internalized within 4T1 cells (Figure
5E). Compared with one-photon excitation fluorescence imaging,
two-photon excitation exhibits high focal spot and resolution
Inspiring the efficient two-photon absorption of TPA-COF,
we further investigated the two-photon fluorescence imaging and
biosafety of TPA-COF in vitro. Dynamic light scattering (DLS)
measurements on TPA-COF gave the zeta potential of -13.4 mV
and an average diameter of 345 nm with a polydispersity index
(PDI) of 0.189 (Figure 5A). We found that the size and zeta
potential of TPA-COF showed no obvious changes in 72 h,
indicating the stability at the physiological condition. As shown in
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(Figure 5F). The z-stack confocal images were taken
continuously from the bottom to the top via two-photon laser
confocal scanning microscopy (TPLCSM). The image stacks
photon bio-probes for studying the biological processes in cells,
tissues, and mouse models.
were processed by Image
J software to obtain the 3D
Conclusion
reconstruction movie of 4T1 cell. Intense intracellular
luminescence was observed with femtosecond laser pulses at
810 nm, under which no background fluorescence from the 4T1
cells would interfere (Figure S16). Benefiting from the high TPA
cross-section value of TPA-COF, high signal strength can be
obtained. The large TPA cross-section and high photostability of
TPA-COF make it a good candidate for in vivo TPLCSM imaging.
In summary, we have demonstrated that TPA-COF could
work as a promising candidate with efficient TPA performance
by utilizing the unique crystalline feature of COF. It is worth
noting that TPA-COF exhibiting the slipped structure between
the layers, the long-range crystal domain, and the π-conjugation
domain of the corresponding monomer greatly improves the
delocalization of π-electrons, which lead to high dipole value and
TPA activity. When the crystalline feature was accessed, the
formation of COFs led to significant improvement in the TPA
cross-section value per chromophore (the increasement of 30.0-
fold, 5.0-fold compared with ligand and amorphous polymer,
respectively), already surpassing those achieved by traditional
methods such as molecular design and polymerization.
Furthermore, upon the TPA efficiency, the TPA-COF can be
used as enhanced imaging agents for in vitro and in vivo two-
photon fluorescence imaging. We expect that this work will offer
a pathway to overcome aggregation-caused quenching and
acquire near-infrared two-photon excited COFs for future
biomedical applications.
Acknowledgements
This work was financially supported by the National Natural
Science Foundation of China (51903191, 51833007, 21721005
and 51690152) and China Postdoctoral Science Foundation
(Nos. 2019TQ234 and 2019M652693). We thank L. Zhang, H.
Deng (Wuhan University) for their invaluable help and
discussion. All of the animal experiments were conducted under
protocols approved by the Institutional Animal Care and Use
Committee (IACUC) of the Animal Experiment Center of Wuhan
University (Wuhan, China).
Figure 6. (A) Schematic illustrating TPA-COF for tumor imaging in vivo. (B)
The two-photon excited fluorescence imaging of TPA-COF at 4T1 tumor
xenograft in Balb/c mice model (B1, PBS group; B2, TPA-COF group). (C) The
two-photon fluorescence intensity of TPA-COF at different tumor tissue depth.
(D) The two-photon fluorescence imaging of TPA-COF at different tumor
tissue depth.
Conflict of interest
To evidence the feasibility of TPA-COF in vivo, 4T1 tumor
xenograft in Balb/c mice model was established for evaluating
the bio-distribution of TPA-COF on a small animal imaging
system. The two-photon fluorescence imaging was measured by
two-photon electrophysiological microscope (OLYMPUS,
FV1200) after intravenous injection of TPA-COF (Figure 6A).
Considering that the nanoparticles tend to accumulate in tumor
tissue through enhanced permeability and retention (EPR) effect
during in vivo circulation.[17] As shown in Figure 6B, very bright
dot-like fluorescent signal was observed with almost no
background in tumor tissue under 810 nm two-photon excitation.
Taking advantage of the two-photon excitation, Figure 6C and
6D show the images of TPA-COF at different depths with the
maximum detectable depth up to around 150 μm. Compared
with one-photon excitation, two-photon excitation exhibits
deeper tissue penetration (Figure S17). These results also
reveal the great potential of TPA-COF serve as one- and two-
The authors declare no conflict of interest.
Keywords: covalent organic framework • slipped structure •
long-range order • two-photon absorption • fluorescence imaging
[1]
[2]
J. Jiang, Y. Zhao, O. M. Yaghi, J. Am. Chem. Soc. 2016, 138, 3255-
3265.
P. J. Waller, F. Gꢀndara, O. M. Yaghi, Acc. Chem. Res. 2015, 48,
3053-3063.
[3]
[4]
C. S. Diercks, O. M. Yaghi, Science 2017, 355, eaal1585.
a) S. Lin, C. S. Diercks, Y. B. Zhang, N. Kornienko, E. M. Nichols, Y.
Zhao, A. R. Paris, D. Kim, P. Yang, O. M. Yaghi, C. J. Chang, Science
2015, 349, 1208-1213; b) S. Ding, J. Gao, Q. Wang, Y. Zhang, W.
Song, C. Su, W. Wang, J. Am. Chem. Soc. 2011, 133, 19816-19822; c)
H. Xu, J. Gao, D. Jiang, Nat. Chem. 2015, 7, 905; d) C. J. Doonan, D. J.
Tranchemontagne, T. G. Glover, J. R. Hunt, O. M. Yaghi, Nat. Chem.
2010, 2, 235; e) S. Ding, M. Dong, Y. Wang, Y. Chen, H. Wang, C. Su,
This article is protected by copyright. All rights reserved.

10.1002/anie.201912594
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RESEARCH ARTICLE
W. Wang, J. Am. Chem. Soc. 2016, 138, 3031-3037; f) H. Qian, C.
Yang, X. Yan, Nat. Commun. 2016, 7, 12104.
Zhang, H. H. Y. Sung, I. D. Williams, J. W. Y. Lam, K. S. Wong, B. Z.
Tang, ACS Nano 2018, 12, 8145-8159; c) H. Cao, L. Wang, Y. Yang, J.
Li, Y. Qi, Y. Li, Y. Li, H. Wang, J. Li, Angew. Chem. Int. Ed. 2018, 57,
7759-7763.
[5]
[6]
a) E. Jin, M. Asada, Q. Xu, S. Dalapati, M. A. Addicoat, M. A. Bragy, H.
Xu, T. Nakamura, T. Heine, Q. Chen, D. Jiang, Science 2017, 357,
673-676; b) X. Li, Q. Gao, J. Wang, Y. Chen, Z. Chen, H. Xu, W. Tang,
K. Leng, G. Ning, J. Wu, Q. Xu, S. Y. Quek, Y. Lu, K. P. Loh, Nat.
Commun. 2018, 9, 2335.
a) M. J. Miller, S. H. Wei, I. Parker, M. D. Cahalan, Science 2002, 296,
1869-1873; b) D. R. Larson, W. R.Zipfel, R. M. Williams, S. W. Clark, M.
P. Bruchez, F. W. Wise, W. W. Webb, Science 2003, 300, 1434-1436;
c) S. Krol, R.Macrez, F., Docagne, G. Defer, S. Laurent, M. Rahman, M.
J. Hajipour, P. G. Kehoe, M. Matmoudi, Chem. Rev. 2012, 11, 1877-
1903; d) J. P. Celli, B. Q. Spring, I.Rizvi, C. L.Evans, K. S.Samkoe, S.
Verma, B. W. Pogue, T. Hasan, Chem. Rev. 2010, 110, 2795-2838; e) I.
Medintz, H. T. Uyeda, E. R. Goldman, H.Mattoussi, Nat. Mater. 2005, 4,
435; f) M. Q. Zhu, G. F. Zhang, C. Li, M. P. Ardred, E. Chang, R. A.
Drezek, A. D. Q. Li, J. Am. Chem. Soc. 2010, 133, 365-372; g) L. Ji, S.
Griesbeck, T. B. Marder, Chem. Sci. 2017, 8. 846-863.
[7]
[8]
a) H. M. Kim, B. R. Cho, Chem. Rev. 2015, 115, 5014-5055; b) F. Bolze,
S. Jenni, A. Sour, V. Heitz, Chem. Commun. 2017, 53, 12857-12877.
M. Albota, D. Beljonne, J. L. Bredas, J. E. Ehrlich, J. Y.Fu, A. A. Heikal,
S. E. Hess, T.Kogej, M. D. Levin, S. R. Marder, D. McCord-Maughon, J.
W. Perry, H. Rockel, M. Rumi, G. Subramaniam, W. W. Webb, X. L. Wu,
C. Xu, Science 1998, 281, 1653-1656.
[9]
a) F. Terenziani, C. Katan, E.Badaeva, S.Tretiak, M. Blanchard-Desce,
Adv. Mater. 2008, 20, 4641-4678; b) Y. Jin, Y. Hu, W. Zhang, Nat. Rev.
Chem. 2017, 1, 1; c) S. Y. Ding, W. Wang, Chem. Soc. Rev. 2013, 42,
548-568; d) R. Medishetty, L. Nemec, V. Nalla, S.Henke, M.Samoc, K.
Reuter, R. A. Fischer, Angew. Chem. Int. Ed. 2017, 56, 14743-14748.
[10] a) S. Kim, Q. Zheng, G. S. He, D. J. Bharali, H. E. Pudavar, A. Baev, P.
N. Prasad, Adv. Funct. Mater. 2006, 16, 2317-2323; b) G. S. He, L. S.
Tan, Q. D. Zheng, P. N. Prasad, Chem. Rev. 2008, 108, 1245-1330.
[11] a) R. Medishetty, J. K. Zareba, D. Mayer, Marek. Samoc, R. A. Fischer,
Chem. Soc. Rev. 2017, 46, 4976-5004; b) E. Collini, C. Ferrante, R.
Bozio, A.Lodi, G. Ponterini, J. Mater. Chem. 2006, 16, 1573-1578; c) G.
P. Bartholomew, M. Rumi, S. J. K. Pond, J. W. Perry, S. Tretiak, G. C.
Bazan, J. Am. Chem. Soc. 2004, 126, 11529-11542; d) J. Y. Zeng, M. Z.
Zou, M. K. Zhang, X. S. Wang, X. Zeng, H. Cong, X. Z. Zhang, ACS
Nano 2018, 12, 4630-4640; e) J. Y. Zeng, X. S. Wang, W. F. Song, H.
Cheng, X. Z. Zhang, Adv. Therap. 2019, 2, 1800100.
[12] a) N. Huang, P. Wang, D. Jiang, Nat. Rev. Mater. 2016, 1, 16068; b) A.
P. Cote, A. I. Benin, N. W. Ockwig, M. O’Keeffe, A. J. Matzger, O. M.
Yaghi, Science 2005, 310, 1166-1170; c) X. Feng, X. Ding, D. Jiang,
Chem. Soc. Rev. 2012, 41, 6010-6022; d) J. L. Segura, M. J.
Mancheno, F. Zamora, Chem. Soc. Rev. 2016, 45, 5635-5671.
[13] Y. Zhou, F. Meng, X. Zhao, S. Feng, M. Jiang, Chem. Phys. 2001, 269,
441-445.
[14] a) T. Ishi-i, N. Nakamura, S. Amemori, K. Kasatani, H. Gorohmaru, M.
Ishida, M. Shigeiwa, Dyes. Pigments 2013, 99, 14-19; b) Z. Zhao, P. Lu,
J. W. Y. Lam, Z. Wang, C. Y. K. Chan, H. H. Y. Sung, I. D. Williams, Y.
Ma. B. Z. Tang, Chem. Sci. 2011, 2, 672-675.
[15] a) M. Pawlicki, H. A. Collins, R. G. Denning, H. L. Anderson, Angew.
Chem. Int. Ed. 2009, 48, 3244-3266; b) L. Ascherl, T. Sick, J. T.
Margral, S. H. Lapidus, M. Calik, C. Hettstedt, K. Karaghiosoff, M.
Doblinger, T. Clark, K. W. Chapman, F. Auras, T. Bein, Nat. Chem.
2016, 8, 310; c) J. Y. Zeng, M. K. Zhang, M. Y. Peng, D. Gong, X. Z.
Zhang, Adv. Funct. Mater. 2018, 28, 1705451; d) J. Y. Zeng, X. S.
Wang, Y. D. Qi, Y. Yu, X. Zeng, X. Z. Zhang, Angew. Chem. Int. Ed.
2019, 131, 5748-5752.
[16] a) M. M. Alam, M. Chattopadhyaya, S. Chakrabarti, K. Ruud, Acc.
Chem. Res. 2014, 47, 1604-1612; b) L. Sun, W. Zhu, W. Wang, F.
Yang, C. Zhang, S. Wang, X. Zhang, R. Li, H. Dong, W. Hu, Angew.
Chem. Int. Ed. 2017, 56, 7831-7835.
[17] a) C. L. Sun, J. Li, X. Z. Wang, R. Shen, S. Liu, J. Q. Jiang, T. Li, Q. W.
Song, Q. Liao, H. B. Fu, J. N. Yao, H. L. Zhang, Chem 2019, 5, 600-
616; b) Z. Zheng, T. Zhang, H. Liu, Y. Chen, R. T. K. Kwok, C. Ma, P.
This article is protected by copyright. All rights reserved.

10.1002/anie.201912594
Angewandte Chemie International Edition
RESEARCH ARTICLE
Table of Contents
RESEARCH ARTICLE
A benzothiadiazole-based
covalent organic
Jin-Yue Zeng, Xiao-Shuang
Wang, Bo-Ru Xie, Min-Jie
Li, and Xian-Zheng Zhang*
framework with slipped
structure was reported to
promote the two-photon
adsorption performance and
overcome the aggregation-
caused emission quenching
of the chromophores for
improving near-infrared two-
photon excited fluorescence
imaging.
Page No. – Page No.
Slipped Structure of
Covalent Organic
Framework Facilitates
Two-Photon Adsorption
for Improving Near-
Infrared Excited
Fluorescence Imaging
This article is protected by copyright. All rights reserved.