The regulation of biothiol-responsive performance and bioimaging application of benzo[c][1,2,5]oxadiazole dyes

Article abstract of DOI:10.1016/j.cclet.2020.02.047

The different oxidation states of sulphur atom play a significant role on functional materials. In this work, a aryl-thioether and its sulphone substituted benzo[c][1,2,5]oxadiazole dyes were synthesized and utilized to determine thiol-containing amino ac

Full text of DOI:10.1016/j.cclet.2020.02.047

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Contents lists available at ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
Communication
The regulation of biothiol-responsive performance and bioimaging
application of benzo[c][1,2,5]oxadiazole dyes
Dongyang Lia, Weijie Chena, Sheng Hua Liua, Xiaoqiang Chenb, Jun Yina,b,
*
a
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, Hubei International Scientific and Technological Cooperation Base of Pesticide and
Green Synthesis, International Joint Research Center for Intelligent Biosensing Technology and Health, College of Chemistry, Central China Normal University,
Wuhan 430079, China
b
State Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Jiangsu National Synergetic Innovation Center for
Advanced Materials (SICAM), Nanjing Tech University, Nanjing 211816, China
A R T I C L E I N F O
A B S T R A C T
Article history:
Available online xxx
The different oxidation states of sulphur atom play a significant role on functional materials. In this work,
a aryl-thioether and its sulphone substituted benzo[c][1,2,5]oxadiazole dyes were synthesized and
utilized to determine thiol-containing amino acids. The result of selectivity experiments showed they
detected the cysteine and homocysteine under physiological condition with negligible interference from
other amino acids. In comparison to the thioether dye, the sulphone-based dye exhibited much faster
response time for Cys and Hcy. However, the sulphone restricted its thiol-reactivity and bioimaging
performance in living cells. By reducing the oxidation state of sulphur atom, we amazedly found that the
sulfoxide-based dye still maintained high selectivity ultrafast response time for Cys/Hcy under
physiological condition. It was worth mentioning that it also had high reactivity and good bioimaging
performance that sulfone compounds did not have.
Keywords:
Benzo[c][1,2,5]oxadiazole dye
Sulfoxide
Sulphone
Thiol response
© 2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Published by Elsevier B.V. All rights reserved.
Thiol-containing amino acids, e.g., cysteine (Cys), homocysteine
(Hcy) and glutathione (GSH), play significant role in maintaining
redox homeostasis in biological systems [1]. Abnormal alterations
of their concentrations considered to be signals of various
pathogenesis and dysfunction in living systems are closely
associated with many human diseases such as AIDS, Alzheimer
’s, as well as cancer, liver damage, growth retardation and
cardiovascular diseases [2]. Accordingly, numerous efforts have
been paid to the development of simple and effective methods to
rapidly track biothiols in biological systems. Recently, fluorescence
probes and bioimaging technology [3] have made great achieve-
ments in development of biothiol-responsive fluorescent probes
due to its excellent sensitivity, high selectivity and excellent
biocompatibility [4,5].
and sulfonamide as the detecting group to track the thiol level in
living cells, tissues and in vivo [6]. However, these probes exhibited
a relatively slow response time. To promote the response rate of
fluorescent probes, some new detecting groups was reported
constantly. For instance, the thioether-type detecting group
involving the mechanism of nucleophilic substitution was installed
on all kinds of fluorophores to construct the thiol-responsive
fluorescent probes by some groups [7,8]. Based on the mechanism
of nucleophilic substitution of these thiol-responsive fluorescent
probes, varying the oxidation state of sulphur atom would possibly
change the activity of nucleophilic substitution [9]. Accordingly, in
this work, we proposed an effective oxidation strategy
to synthesize thiol-responsive benzo[c][1,2,5]oxadiazole dyes
containing sulphur atom with different oxidation state, and
investigated the effect of the oxidation state of sulphur atom on
thiol-responsive rate and their bioimaging application.
In our group, we have developed a type of thiol-specific
fluorescent probes by employing the naphthalimide as fluorophore
Dyes NBD-S and NBD-SO2 were obtained according to the
synthetic route in Fig. 1A. Firstly, thiophenol was treated with the
commercially available 4-chloro-7-nitrobenzo[c][1,2,5]thiadiazole
(NBD-Cl) to yield the targeting thioether (NBD-S). Subsequent
oxidation produced the sulphone-based dye (NBD-SO2). Their
structures have been well characterized by 1HNMR, 13C NMR and
mass spectroscopies (Supporting information). In particular, their
single crystals suitable for crystallographic analysis were obtained
* Corresponding author at: Key Laboratory of Pesticide and Chemical Biology,
Ministry of Education, Hubei International Scientific and Technological Cooperation
Base of Pesticide and Green Synthesis, International Joint Research Center for
Intelligent Biosensing Technology and Health, College of Chemistry, Central China
Normal University, Wuhan, 430079, China.
E-mail address: yinj@mail.ccnu.edu.cn (J. Yin).
https://doi.org/10.1016/j.cclet.2020.02.047
1001-8417/© 2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: D. Li, et al., The regulation of biothiol-responsive performance and bioimaging application of benzo[c][1,2,5]
oxadiazole dyes, Chin. Chem. Lett. (2020), https://doi.org/10.1016/j.cclet.2020.02.047

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Fig. 1. (A) The synthetic of dyes NBD-S and NBD-SO2. (B) The crystal structure of NBD-S. (C) The crystal structure of NBD-SO2. (D) The frontier molecular orbital profiles of
NBD-S and NBD-SO2 based on TD-DFT (B3LYP/6-31G*) calculations.
by slow diffusion of hexane into a THF solution of NBD-S and a
CH2Cl2 solution of NBD-SO2 at room temperature, respectively.
From the crystral structure of NBD-S in Fig. 1B, there were multiple
weak intermolecular interactions including CÀÀHÁ Á ÁO, CÀÀHÁ Á ÁS,
CÀÀHÁ Á ÁN and pÁÁÁp interactions while NBD-SO2 in Fig. 1C mainly
involved in two weak interactions including CÀÀHÁ Á ÁO and
CÀÀHÁÁÁp interaction (Tables S1-S3, Figs. S1 and S2 in Supporting
information). These multiple interactions led to the highly ordered
stacking in crystalline phases.
To assess the electronic properties of dyes, time-dependent
density functional theory (TD-DFT) calculations were carried out at
the B3LYP/6-31G* level with the Gaussian 09 program to
investigate their frontier molecular orbitals and electronic
transitions. In Fig. 1D, the electron density of HOMO and LUMO
of NBD-S predominantly assigned to NBD moiety. Two intense
transitions were predicted at about 388 nm with a larger oscillator
strength of 0.3008 (HOMO → LUMO) and 285 nm with a larger
oscillator strength of 0.0918 (HOMO → LUMO + 1), implying that
dye NBD-S had weak fluorescence for weak charge transfer
(Table S4 in Supporting information). For dye NBD-SO2, the HOMO
orbital was predominantly assigned to the phenylsulphone unit
while the LUMO orbital was mainly located the NBD moiety, and
there are two intense transitions with a larger oscillator strength of
0.1220 (HOMO-2 → LUMO) and 0.1084 (HOMO-1 → LUMO) at
325 nm and 368 nm, respectively. The result suggested that NBD-
SO2 was non-fluorescent probably due to a process of electron
transfer.
In view of the sensitivity of thioether group towards biothiols,
their UV–vis absorption and fluorescent spectra were explored in
HEPES buffer solution (10 mmol/L, pH 7.4) containing 1% DMSO to
evaluate the selectivity of dyes NBD-S and NBD-SO2. In UV–vis
absorption spectra (Fig. S3 in Supporting information), dyes NBD-S
and NBD-SO2 showed similar absorption changes from 426 nm to
480 nm upon addition of Cys and Hcy, respectively. In fluorescence
spectra, the blank solution of dyes NBD-S and NBD-SO2 were
almost non-fluorescent, which were well in agreement with the
result of above theoretical calculation. However, remarkable
fluorescence enhancements at 550 nm were found upon the
addition of Cys and Hcy, respectively, as shown in Figs. 2A and B,
while other amino acids including GSH only induced negligible
fluorescence changes. And according to the changes of fluores-
cence intensity, it was found that the reaction equilibrium of dye
Fig. 2. Fluorescence changes of dyes NBD-S (A) and NBD-SO2 (B) (10
(10 mmol/L, pH 7.4) containing 1% DMSO. Florescence intensity changes at 550 nm of dyes NBD-S (C) and NBD-SO2 (D) (10
in the presence of various analytes (100 mol/L). Analytes 1-14: (1) GSH, (2) Hcy, (3) Cys, (4) -Glu, (5) Ala, (6) Tyr, (7) Lys, (8)
(14) Phe. lex = 475 nm and slit width of 11 nm  9 nm.
m
mol/L) upon the addition of Cys, Hcy and other various analytes (100
mol/L) toward Cys (blue bars) and Hcy (red bars)
-Glu, (9) Ser, (10) His, (11) Arg, (12) Met, (13) Gln,
mmol/L) in HEPES buffer solution
m
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D
Please cite this article in press as: D. Li, et al., The regulation of biothiol-responsive performance and bioimaging application of benzo[c][1,2,5]
oxadiazole dyes, Chin. Chem. Lett. (2020), https://doi.org/10.1016/j.cclet.2020.02.047

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NBD-SO2 was lower than dye NBD-S probably as a result of inferior
reactivity with Cys/Hcy. This observation was consistent with
previous report [9]. Subsequently, the further fluorescence
competitive assays were performed to assess the interferences
from other analytes. The results in Figs. 2C and D indicated that Cys
and Hcy still induced distinct fluorescence changes of dyes NBD-S
and NBD-SO2 in the presence of other amino acids, strongly
suggesting that dyes NBD-S and NBD-SO2 had high specificity
towards Cys/Hcy with little interferences from other similar
analytes. For the sensing mechanism, we supposed that the spectra
changes were caused by the addition of Cys/Hcy through the
nucleophilic substitution reaction to produce the fluorescent
substituted products [10], which were confirmed by ESI mass
spectrometry (Fig. S4 in Supporting information).
the dye NBD-S, the responsibility of dye NBD-SO2 toward biothiols
was significantly improved under same condition, and it could
selectively detect Cys at pH 5.0 (Figs. S8B, S9 and S10 in Supporting
information).
The above investigation in vitro confirmed that dyes NBD-S and
NBD-SO2 could be used to visualize the level of Cys/Hcy in living
cells. Accordingly, the cytotoxicity of dyes was investigated by CCK-
8 assay. The result suggested that dye NBD-S (Fig. S11A in
Supporting information) had low cytotoxicity. For the dye NBD-
SO2, it also exhibited low cytotoxicity partially due to its poor cell
permeability (Fig. S11B in Supporting information). Subsequently,
dyes NBD-S and NBD-SO2 were utilized to monitor intracellular Cys
and Hcy. As could be observed by viewing Fig. 4, a quite strong
fluorescence signal (Fig. 4B) was found in HeLa cells when they
Next, their sensing capability for Cys/Hcy with different
concentrations in HEPES buffer solution (10 mmol/L, pH 7.4)
containing 1% DMSO was investigated. In UV–vis absorption
spectra, the main absorption peak of dye NBD-S at 428 nm
were incubated with dye NBD-S (5 mmol/L) for 30 min, indicating
that dye NBD-S was capable of permeating into cells and
perceiving the existence of endogenous Cys and Hcy. Moreover,
it was further verified by the subsequent control experiments. The
HeLa cells pre-treated with the biothiol-blocking reagent NEM
(1 mmol/L) for 30 min and then incubated with dye NBD-S for
30 min didn’t show fluorescence signal in Fig. 4C. As expected, the
gradually decreased and
a new peak at 484 nm emerged
concurrently with a well-defined isosbestic point at 438 nm upon
the addition of Cys/Hcy (Fig. S5 in Supporting information). And
the corresponding fluorescence intensity at 550 nm showed a
gradual enhancement along with the addition of Cys/Hcy (Figs. 3A
and B). It was worth mentioning that the fluorescence intensity
changes were linearly proportional to the Cys/Hcy concentration
(Fig. S6 in Supporting information). According to the formula of
addition of Cys in Fig. 4D and Hcy in Fig. 4E (100 mmol/L) to the
HeLa cells pre-treated by NEM induced a significant fluorescence,
while no obvious change was detected upon the addition of GSH in
Fig. 4F. These results indicated that NBD-S can be used to mark the
Cys/Hcy in living cells. For the sulphone NBD-SO2, the bioimaging
experiments showed that NBD-SO2 had poor cell permeability in
comparison to the dye NBD-S (Figs. S11B and S12 in Supporting
information).
3
s
/k [11], the detection limits of dye NBD-S were 9.7 Â 10À8 mol/L
for Cys, and 9.4 Â 10À8 mol/L for Hcy, respectively. These observa-
tions indicated that NBD-S could serve as a promising means for
detecting Cys/Hcy quantitatively.
According to the above investigation, dye NBD-SO2 with higher
oxidation state of sulphur atom had faster responsive rate than
NBD-S, however NBD-S exhibited high reactivity for Cys/Hcy and
better cell membrane permeability. The reported literature
indicated that the sulfoxide group had a good reactivity with
sulfhydryl groups [9]. Accordingly, we guessed justifiably that the
sulphur atom of sulfoxide structure was in the intermediate
valence of thioether and sulphone structures, and the NBD dye
with sulfoxide group would probably have good thiol-reactivity
and cell membrane permeability as well as NBD-S. Moreover, it
possibly had fast responsive time like NBD-SO2. Based on the
consideration, dye NBD-SO was synthesized subsequently by
oxidizing NBD-S under the condition of less equivalent oxidant and
lower temperature, as shown in Fig. 5A. Its structure was also well-
confirmed by 1H NMR, 13C NMR and mass spectroscopies
(Figs. S30-S32 in Supporting information). Furthermore, we also
obtained its single crystals by slow diffusion of hexane into a
CH2Cl2 solution of NBD-SO at room temperature. The crystallo-
graphic analysis (Fig. 5B, Tables S5 and S6 in Supporting
information) verified the sulphoxide structure, and the stacking
involved in multiple weak intermolecular interactions, e.g., CÀÀHÁ Á Á
Then, the time-dependent response of dyes NBD-S and NBD-
SO2 (10 mmol/L) towards Cys, Hcy and GSH (100 mmol/L) were
tested in HEPES buffer solution (10 mmol/L, pH 7.4) containing 1%
DMSO. As shown in Fig. 3C, the fluorescent intensity of dye NBD-S
at 550 nm gradually increased to its maximum around within
50 min for Cys and Hcy while GSH did not follow such significance
fluorescence change (Figs. S7A-C in Supporting information). As
comparison, its oxidation sulphone-based dye NBD-SO2 respond-
ing Cys or Hcy to reach the maximum was around within 1 min and
15 min in Fig. 3D (Figs. S7D-F in Supporting information),
respectively. The result suggested that the different oxidation
state of leaving group sulphur had a large influence on the
response time of biothiols.
In our previous work, we found that the different pH
environment had a large effect for the biothiols responsibility
[7e]. Therefore, their responsibility in HEPES buffer solution
(10 mmol/L) containing 1% DMSO at various pH values was studied.
The fluorescence spectra revealed that the optimal conditions for
dyes NBD-S (Fig. S8A in Supporting information) to detect Cys/Hcy
was around pH 7.0, indicating that the dye might be suitable to
monitor biothiols under physiological conditions. In comparison to
O, CÀÀHÁ Á Á
p interactions (Fig. S13 in Supporting information). To
Fig. 3. Fluorescence spectra of dye NBD-S upon the gradual addition of Cys (A) or Hcy (B) (0–8 equiv.) in HEPES buffer solution (10 mmol/L, pH 7.4) containing 1% DMSO. The
time-dependent fluorescence intensity changes at 550 nm of dyes NBD-S (C) and NBD-SO2 (D) (10
(10 mmol/L, pH 7.4) containing 1% DMSO. lex = 475 nm and slit width of 11 nm  9 nm.
mmol/L) with Cys, Hcy or GSH (100 mmol/L) in HEPES buffer solution
Please cite this article in press as: D. Li, et al., The regulation of biothiol-responsive performance and bioimaging application of benzo[c][1,2,5]
oxadiazole dyes, Chin. Chem. Lett. (2020), https://doi.org/10.1016/j.cclet.2020.02.047

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Fig. 4. Confocal microscope images of dye NBD-S responding to biothiols in HeLa cells. (A) Fluorescence images of HeLa cells as control. (B) Fluorescence images of HeLa cells
incubated with dye NBD-S (5 mol/L) for 30 min. (C) Fluorescence images of HeLa cells pre-treated with NEM (1 mmol/L) for 30 min, and incubated with dye NBD-S (5 mol/L)
for 30 min. (D-F) Fluorescence images of HeLa cells pre-treated with NEM (1 mmol/L, 30 min), then treated with Cys (D), Hcy (E) or GSH (F) (100 mol/L, 30 min), and then
incubated with dye NBD-S (5 mol/L, 30 min). (Top) Images of green channel. (Middle) Images of bright field. (Bottom) Overlay of bright field and green channel.
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Fig. 5. (A) The synthetic of dye NBD-SO. (B) The single crystal structure of NBD-SO. (C) The frontier molecular orbital profiles of NBD-SO based on TD-DFT (B3LYP/6-31G*)
calculations.
gain insight into the electronic properties of NBD-SO, the similar
TD-DFT calculation was carried out. From the frontier molecular
orbitals containing the main electronic transitions in Fig. 5C, there
was an analogous electronic distribution as NBD-SO2. The electron
density of HOMO orbital was predominantly distributed to the
aryl-sulphoxide group whereas the electron density of the LUMO
orbital mainly assigned to NBD component. More, there were two
main absorption bands belong to S0-S4 transition at around 364 nm
demonstrated a larger oscillator strength of 0.0949 corresponding
to 57% contribution from the HOMO-2 to LUMO, and S0-S7
transition at around 318 nm demonstrated a large oscillator
strength of 0.1155 corresponding to 68% contribution from the
HOMO-3 to LUMO, implying that dye NBD-SO involved in a process
of electron transfer.
For dye NBD-SO, we firstly investigated its selectivity towards
various biothiols. In UV–vis absorption spectra (Fig. S14 in
Supporting information), it was found that addition of Cys and
Hcy induced a new similar absorption at 480 nm, respectively.
Furthermore, obvious fluorescence changes at 550 nm in HEPES
buffer solution (10 mmol/L, pH 7.4) containing 1% DMSO were
observed when only Cys and Hcy were added to its buffer solution
in Fig. 6A. And the competitive experiment further indicated that
Please cite this article in press as: D. Li, et al., The regulation of biothiol-responsive performance and bioimaging application of benzo[c][1,2,5]
oxadiazole dyes, Chin. Chem. Lett. (2020), https://doi.org/10.1016/j.cclet.2020.02.047

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Fig. 6. (A) Fluorescent spectra of dye NBD-SO (10
m
mol/L) upon the addition of Cys, Hcy and other various analytes (100
mmol/L) in HEPES buffer solution (10 mmol/L, pH 7.4)
containing 1% DMSO. lex = 475 nm and slit width of 11 nm  9 nm. (B) Fluorescence spectra of dye NBD-SO upon the gradual addition of Cys (0-8 equiv.) in HEPES buffer
solution (10 mmol/L, pH 7.4) containing 1% DMSO. lex = 475 nm and slit width of 11 nm  9 nm. (C) Fluorescence spectra of dye NBD-SO upon the gradual addition of Hcy
(0-8 equiv.) in HEPES buffer solution (10 mmol/L, pH 7.4) containing 1% DMSO. lex = 475 nm and slit width of 11 nm  9 nm. (D) The time-dependent fluorescence intensity
changes at 550 nm of dye NBD-SO (10 mmol/L) with Cys, Hcy or GSH (100 mmol/L) in HEPES buffer solution (10 mmol/L, pH 7.4) containing 1% DMSO. lex = 475 nm and slit
width of 11 nm  9 nm.
dye NBD-SO had high specificity towards Cys/Hcy (Fig. S15 in
Supporting information). Moreover, the reaction mechanism of
nucleophilic substitution reaction was predicted by ESI mass
spectrometry (Fig. S16 in Supporting information).
under weakly acidic condition were also detected (Figs. S20-22
in Supporting information).
These findings described above strongly indicated that the
NBD-SO dye was capable of serving as a fluorescence indicator to
track the Cys and Hcy. As expected, dye NBD-SO was able to enter
the cell easily and had low cytotoxicity (Fig. S23 in Supporting
information). By viewing the confocal microscope images in Fig. 7,
bright green fluorescence signals were detected when the non-
Then, titration experiment was made to further understand the
quantitative ability of dye NBD-SO responding to various concen-
trations of Cys/Hcy (0–8 equiv.) by UV–vis absorption spectra
(Fig. S17 in Supporting information) and fluorescence spectra in
Figs. 6B and C. Clearly, there was a good linear correlation between
fluorescence intensity at 550 nm and the concentrations of
Cys/Hcy (Fig. S18 in Supporting information). And the detection
limits of dye NBD-SO were calculated to be 1.97 Â 10À7 mol/L for
Cys and 1.64 Â10À7 mol/L for Hcy, suggesting that it could be
utilized for the determination of Cys/Hcy. Especially, the reaction
fluorescent HeLa cells was incubated with NBD-SO (5
mmol/L) for
30 min. Combining the fact that there was no obvious fluorescence
signal when NBD-SO was incubated with HeLa cells pre-treated by
NEM indicated that the NBD-SO could detect endogenous
biothiols. Moreover, significant fluorescence signals appearing in
the NEM pre-treated HeLa cells resulted from the addition of only
Cys and Hcy, respectively. These performances indicated that
NBD-SO could be utilized as a tool to monitor levels of Cys/Hcy in
living cells.
In conclusion, we have developed a type of fluorescent dyes
based on benzo[c][1,2,5]oxadiazole by linking a aryl-sulphur
species. Investigation on the response behavior towards amino
acids indicated that they were capable of selectively detecting
kinetics of dye NBD-SO (10
mmol/L) in the presence of biothiols
(100 mol/L) showed that its response times toward Cys and Hcy
m
were within 1 min, 15 min in Fig. 6D, respectively (Fig. S19 in
Supporting information). By analyzing the fluorescence intensity
and response time of all dyes, dye NBD-SO possessed good
reactivity and fast response ability. Similar results of Cys/Hcy-
selectivity under physiological conditions and Cys-selectivity
Fig. 7. Confocal microscope images of dye NBD-SO responding to biothiols in HeLa cells. (A) Fluorescence images of HeLa cells as control. (B) Fluorescence images of HeLa cells
incubated with dye NBD-SO (5 mol/L) for 30 min. (C) Fluorescence images of HeLa cells pre-treated with NEM (1 mmol/L) for 30 min, and incubated with NBD-SO (5 mol/L)
for 30 min. (D-F) Fluorescence images of HeLa cells pre-treated with NEM (1 mmol/L, 30 min), then treated with Cys (D), Hcy (E) or GSH (F) (100 mol/L, 30 min), and then
incubated with dye NBD-SO (5 mol/L, 30 min). (Top) Images of green channel. (Middle) Images of bright field. (Bottom) Overlay of bright field and green channel.
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Cys/Hcy over other amino acids containing glutathione. Interest-
ingly, the sulphur-oxidizing dyes sulphone and sulfoxide exhibited
a faster response time for Cys/Hcy. Especially, the sulfoxide dye
presented a better reactivity and membrane penetrability com-
pared with sulphone-based benzo[c][1,2,5]oxadiazole dye, and
was able to track the Cys/Hcy in living cells. Our work provides an
efficient strategy to change the responsive performance of
fluorescent dyes through a simple oxidation approach. We believe
it will be able to be applied in the design of fine fluorescent dyes in
future.
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This work was supported by the National Natural Science
Foundation of China (Nos. 21676113, 21402057, 21772054,
21472059), Distinguished Young Scholar of Hubei Province
(No. 2018CFA079), Youth Chen-Guang Project of Wuhan (No.
2016070204010098), the 111 Project B17019, the Ministry-Prov-
ince Jointly Constructed Base for State Key Lab-Shenzhen Key
Laboratory of Chemical Biology (Shenzhen), the State Key
Laboratory of Materials-Oriented Chemical Engineering (No.
KL17-10), Open Project Fund of Key Laboratory of Natural
Resources of Changbai Mountain & Functional Molecules (Yanbian
University), Ministry of Education (No. NRFM201701), the Foun-
dation of Key Laboratory of Synthetic and Biological Colloids,
Ministry of Education, Jiangnan University (No. JDSJ2017-07), the
Self-determined Research Funds of CCNU from the Colleges' Basic
Research and Operation of MOE (No. CCNU18TS012). We thank
Professor Xin Zhou and Miss Yuanzhi Shen for their great help.
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Appendix A. Supplementary data
Supplementary material related to this article can be
found, in the online version, at doi:https://doi.org/10.1016/j.
cclet.2020.02.047.
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Please cite this article in press as: D. Li, et al., The regulation of biothiol-responsive performance and bioimaging application of benzo[c][1,2,5]
oxadiazole dyes, Chin. Chem. Lett. (2020), https://doi.org/10.1016/j.cclet.2020.02.047