Fluorescein-derived fluorescent probe for cellular hydrogen sulfide imaging

Article abstract of DOI:10.1016/j.cclet.2014.05.010

In this work, a fluorescein-derived fluorescent probe for H₂S based on the thiolysis of dinitrophenyl ether is reported. This probe exhibits turn-on fluorescence imaging of H₂S in living cells and bulk solutions with excellent selectivity. The reaction mechanism was explained by means of absorption, fluorescence and HPLC-MS.

Full text of DOI:10.1016/j.cclet.2014.05.010

G Model
CCLET 2988 1–5
Chinese Chemical Letters xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
1
2
Original article
3
4
Fluorescein-derived fluorescent probe for cellular
hydrogen sulfide imaging
5
6
Q1 Hui-Ying Liu a,b,1, Miao Zhao b,1, Qing-Long Qiao b, Hai-Jing Lang b,
b,
Jing-Zhe Xu a, , Zhao-Chao Xu
*
*
7
8
a Department of Chemistry, Yanbian University, Yanji 133002, China
b Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
A R T I C L E I N F O
A B S T R A C T
Article history:
In this work, a fluorescein-derived fluorescent probe for H2S based on the thiolysis of dinitrophenyl ether
is reported. This probe exhibits turn-on fluorescence imaging of H2S in living cells and bulk solutions
with excellent selectivity. The reaction mechanism was explained by means of absorption, fluorescence
and HPLC–MS.
Received 24 January 2014
Received in revised form 24 March 2014
Accepted 4 April 2014
Available online xxx
ß 2014 Jing-Zhe Xu and Zhao-Chao Xu. Published by Elsevier B.V. on behalf of Chinese Chemical
Society. All rights reserved.
Keywords:
Fluorescent probe
H2S
Fluorescein
Thiolysis
9
10
1. Introduction
fluorescent probes offer higher sensitivity, real-time imaging, 31
and higher spatiotemporal resolution, and have more potential to 32
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
Hydrogen sulfide (H2S) is well known as a toxic gas with the
characteristic smell of rotten eggs. However, recent investigations
have demonstrated that H2S is the third most important
gasotransmitter for regulating cardiovascular, neuronal, immune,
endocrine, and gastrointestinal systems, along with nitric oxide
and carbon monoxide [1]. H2S is produced endogenously in
be a suitable tool. So far, a number of fluorescent probes for H2S 33
have been reported based on specific chemical reactions by 34
taking advantage of the reducing or nucleophilic properties of H2S 35
[11–20]. Most of these probes display high selectivity for H2S over 36
other thiols such as cysteine due to the nature of reaction type 37
recognition. However, in consideration of issues related specifi- 38
cally to application in biological tissues, more research is needed to 39
improve the biocompatibility, absorption coefficient and fluores- 40
cent quantum yield, visible light excitation, photostability and 41
mammalian systems from
by two pyridoxal-50-phosphate-dependent enzymes, cystathio-
nine -synthase (CBS) and cystathionine -lyase (CSE) [2]. As a
L-cysteine in reactions catalyzed mainly
b
g
signal molecule, it modulates neuronal transmission [2], relaxes
smooth muscle [3], regulates release of insulin [4] and is involved
in inflammation [5]. The endogenous levels of H2S are believed to
be related to some diseases like Alzheimer’s disease [6], Down’s
syndrome [7], diabetes [8] and liver cirrhosis [9]. Inhibitors of H2S
and H2S donors have shown potential for therapeutic exploitation
of H2S [10] in animal disease models. Thus, visualization of the
distribution and concentration of H2S in living systems would be
very important and helpful to elucidate the biological roles of H2S.
Compared with reported methods such as colorimetric analysis,
electrochemical analysis and gas chromatography, small molecule
signal-to-noise ratio (SNR) of H2S fluorescent probes.
42
Fluorescein and its derivatives have been the most widely used 43
class of organic dyes by biologists and chemists as safe 44
fluorophores to design fluorescent probes, labels and immunolog- 45
ical probes, for their excellent photophysical properties, such as 46
high absorption coefficient, excellent fluorescent quantum yield 47
and great photostability [21,22]. For example, folate conjugated to 48
fluorescein iso-thiocyanate for targeting FR-a was reported as the 49
first in-human use of intra-operative tumor-specific fluorescence 50
imaging for real-time surgical visualization of tumor tissue in 51
patients with suspected ovarian cancer [23]. Spirolactone deriva- 52
tives are nonfluorescent and colorless, whereas ring-opening of 53
the corresponding lactone gives rise to strong fluorescence and a 54
green color [24]. Because of the high SNR turn-on response, taking 55
advantages of the spiroring-opening mechanism, a large number of 56
*
Corresponding authors.
E-mail addresses: jingzhex@ybu.edu.cn (J.-Z. Xu), zcxu@dicp.ac.cn (Z.-C. Xu).
These authors contributed equally to this work.
1
http://dx.doi.org/10.1016/j.cclet.2014.05.010
1001-8417/ß 2014 Jing-Zhe Xu and Zhao-Chao Xu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Please cite this article in press as: H.-Y. Liu, et al., Fluorescein-derived fluorescent probe for cellular hydrogen sulfide imaging, Chin.
Chem. Lett. (2014), http://dx.doi.org/10.1016/j.cclet.2014.05.010

G Model
CCLET 2988 1–5
2
H.-Y. Liu et al. / Chinese Chemical Letters xxx (2014) xxx–xxx
2. Experimental
70
Unless otherwise stated, all reagents were purchased from
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
commercial suppliers and used without further purification. 1H
NMR and 13C NMR spectra were recorded on a VARIAN INOVA-400
spectrometer, using TMS as an internal standard. UV–visible
spectra were collected on an Agilent Cary 60 UV/vis spectropho-
tometer. Fluorescence measurements were performed on an
Agilent CARY Eclipse fluorescence spectrophotometer (Serial No.
FL0812-M018). HPLC–MS analysis was performed on Agilent 6540
UHD Accurate-Mass Q-TOF LC/MS using an HPLC system composed
of a pump (Agilent ZORBAX Eclipse Plus C18 2.1 mm ꢀ 50 mm) and
a DAD detector (254 nm).
Scheme 1. The reaction of compound 1 with H2S.
Synthesis of 1: Fluorescein (332 mg, 1 mmol) and 1-bromine-
2,4-dinitrobenzene (543 mg, 2.2 mmol, 2.2 equv.) were added to
10 mL anhydrous DMF. After stirring at room temperature for 12 h,
the solvent was removed under reduced pressure to obtain a pale
solid, which was purified by silica gel column chromatography (PE:
EA = 20:1) to afford desired product 1 as a light yellow solid
(544 mg, 82% yield). The synthetic step of the sensor 1 was shown
in Scheme S1 (Supporting information) and the NMR datas of the
sensor 1 were shown in Figs. S1 and S2. Mp 106–108 8C. 1H NMR
57
58
59
60
61
62
63
64
65
66
67
68
69
fluorescent probes have been developed for metal ions, anions and
small molecules in recent years [21,22,25]. Unfortunately, only a
very few fluorescein-derived fluorescent probes have been
designed on the basis of the spiroring-opening mechanism to
image H2S in living cells [26–29].
In this paper, we report a fluorescent probe 1 for detection of
H2S in aqueous solution and living cells (Scheme 1). The two
hydroxyl groups of fluorescein were protected by dinitrophenyl
ether, which acted as the H2S reactive site [30,31]. The synthesis of
1 is quite straightforward and started from the cheap commercially
available material fluorescein. The probe 1 was obtained in one
step in high yield and characterized by 1H NMR, 13C NMR and
HRMS. The experimental details are given in supporting materials.
(400 MHz, CDCl3):
d 8.86 (d, 2H, J = 2.8 Hz), 8.40 (dd, 2H, J = 9.2,
2.8 Hz), 8.08 (d, 1H, J = 7.6 Hz), 7.79–7.69 (m, 2H), 7.26–7.20 (m,
3H), 6.96 (s, 1H), 6.94 (s, 1H), 6.87–6.84 (m, 2H). 13C NMR
(101 MHz, CDCl3):
d 168.66, 155.77, 154.54, 152.24, 142.53,
140.30, 135.65, 130.53, 130.46, 128.97, 126.18, 125.61, 123.83,
0.08
600
0.08
0.06
0.04
0.02
0.00
a
600
400
200
0
b
0.06
0.04
0.02
0.00
500
400
300
200
100
0
0
10 20 30 40 50 60
[NaHS] (eq)
0
10 20 30 40 50 60
[NaHS](eq)
400
500
550
600
650
Wavelength (nm)
Wavelength (nm)
0.06
0.04
0.02
0.00
d
c
0.06
400
300
200
100
0
400
300
200
100
0
0.04
0.02
0.00
0
10
20
30
40
0
10
20
30
40
Time (min)
Time (min)
400
500
550
600
650
Wavelength (nm)
Wavelength (nm)
Fig. 1. (a) UV–vis absorption spectra of 10
emission spectra of 10 mol/L compound 1 in the presence of 0–60 equiv. of H2S in aqueous solution. (c) Time dependence of absorption profiles of 1 (10
30 equiv. H2S. (d) Time dependence of fluorescence profiles of 1 (10 mol/L) with 30 equiv. H2S. ex = 450 nm.
m
mol/L compound 1 in the presence of 0–60 equiv. of H2S in aqueous solution (CH3CN:HEPES = 6:4, pH 7.4). (b) Fluorescent
m
mmol/L) with
m
l
Please cite this article in press as: H.-Y. Liu, et al., Fluorescein-derived fluorescent probe for cellular hydrogen sulfide imaging, Chin.
Chem. Lett. (2014), http://dx.doi.org/10.1016/j.cclet.2014.05.010

G Model
CCLET 2988 1–5
H.-Y. Liu et al. / Chinese Chemical Letters xxx (2014) xxx–xxx
3
122.17, 120.06, 116.92, 116.06, 108.46, 81.03. HRMS (ESI) calcd. for
C
quantum yield of the probe for detecting H2S is 0.564 and the molar 10125678901234
32H17N4O13 [MH+] 665.0792, found 665.0794.
extinction coefficient is 7200 L/mol cm.
125
Culture of Hela cells and fluorescent imaging: Hela was cultured
The fluorescence emission at 525 nm should belong to 126
fluorescein in quinoid form, which resulted from the thiolysis of 127
the dinitrophenyl ether by H2S. To verify this mechanism, the 128
reaction products of 1 with NaHS were analyzed by HPLC–MS 129
(Fig. 2) and the corresponding MS data of the HPLC peaks have been 130
shown in Fig. S5 (Supporting information). The absorption spectra 131
of fluorescein in various solvents were also checked. As shown in 132
Fig. S6 (Supporting information), the absorption peak in the visible 133
region can only be found in protic solvents, which indicates that 134
fluorescein forms a lactone in aprotic solvents, but a quinoid in 135
protic solvents. From that, we can conclude that the peak in Fig. 2b 136
belongs to fluorescein in its quinoid form. We also investigate the
effect of pH on the absorption and fluorescence properties of the
probe within pH range of 2.0–8.0. As shown in Fig. S7 (Supporting 137
information), the changes of the pH affected the properties of the
probe slightly. After reaction for 20 min, as shown in Fig. 2c, the 138
product of fluorescein in its quinoid form was found, which 139
confirmed the reaction mechanism. Interestingly, fluorescein in its 140
lactone form and single dinitrophenyl ether protected compound 2 141
were also observed (Fig. S8 in Supporting information). After 142
another 20 min, the reaction completed and the products 143
contained fluorescein both in quinoid and lactone forms in a 1:4 144
ratio (Fig. 2d). From that, we may conclude that H2S reacts with 1 to 145
release dinitrophenyl ether one by one (Scheme 1). In pure CH3CN, 146
H2S reacted with 1 quickly to form the fluorescent species of 147
fluorescein in its quinoid form (Fig. S9 in Supporting information). 148
However, in the next hour, the fluorescence decreased gradually 149
due to the transformation of fluorescein from the quinoid form to 150
the lactone form (Fig. S10 in Supporting information). It follows that 151
theexistenceoffluoresceininits lactoneform inthe productsshould 152
be ascribed to the large percentage of acetonitrile in mixture 153
solution. Also, we may point out that compound 2 reacts with H2S to 154
in Dulbecco’s modified Eagle’s medium (DMEM, Invitrogen)
supplemented with 10% FBS (fetal bovine serum) in an atmosphere
of 5% CO2 and 95% air at 37 8C. The cells were seeded in 24-well flat-
bottomed plates and then incubated for 48 h at 37 8C under 5% CO2.
Probe 1 (5
mmol/L) was then added to the cells and incubation for
another 30 min followed. The cells were washed three times with
phosphate-buffered saline (PBS). The cells were incubated with
100
mmol/L of H2S for 30 min. Fluorescence imaging was observed
under a confocal microscope (Olympus FV1000) with a 60ꢀ
objective lens.
3. Results and discussion
The absorption and fluorescence properties of 1 were tested in
aqueous solution (CH3CN:HEPES = 6:4, pH 7.4, 50 mmol/L).
Compound 1 exhibited no absorption features in the visible region
(Fig. 1a) and the solution of 1 was colorless (Fig. S3 in Supporting
information). This meant that
1 adopted a closed lactone
conformation which displayed no fluorescence (Fig. 1b). When
0–60 equiv. of NaHS was added to the solution of 1, a new
absorption band centered at 450 nm developed quickly (Fig. 1a)
which induced the color change from colorless to yellow (Fig. S3).
Under UV lamp irradiation, the changes of color before and after
adding H2S are also shown in Fig. S1. Simultaneously, the
fluorescence emission band centered at 525 nm was observed
and increased in intensity (Fig. 1b). We also found that if the
concentration of NaHS was over 30 equiv., the reaction finished
quickly (Insets in Fig. 1a and b). There was good linearity between
the fluorescence intensity and the concentrations of H2S in
the range of 0–140
L (Fig. S4 in Supporting information). Therefore, we used 30 equiv.
of H2S to examine the performance of in all following
mmol/L with a detection limit of 0.57 mmol/
produce fluorescein in its quinoid form firstly (Scheme 1).
155
1
The selectivity of the fluorescent response of 1 to H2S was then 156
examined. Fig. 3 shows the fluorescence response of 1 to various 157
anions and sulfur-containing analytes in aqueous solutions 158
(CH3CN:HEPES = 6:4, pH 7.4). Selective and large fluorescent 159
enhancements (FE, fold) were observed upon addition of NaHS 160
experiments. The time-dependent fluorescence responses were
next detected with the addition of 30 equiv. H2S and the results
showed that the reaction was completed within 40 min (Fig. 1c and
d). Notably, the background fluorescence of 1 is very weak, and
within minutes a high fluorescence increase is observed which
relays the reaction of 1 with H2S (Fig. 1d); therefore, the timescale
allows 1 to sense H2S in real-time intracellular imaging. The
to the solution of 1. The addition of 100 equiv. of Fꢁ, Clꢁ, Brꢁ, ClO4
,
,
,
161
162
163
ꢁ
2ꢁ
2ꢁ
HCO3ꢁ, NO3ꢁ, NO2ꢁ, PO43ꢁ, HPO42ꢁ, H2PO4ꢁ, P2O74ꢁ, S2O3
S2O42ꢁ, S2O52ꢁ, S2O82ꢁ, SO3ꢁ, N3ꢁ, SCNꢁ, CO32ꢁ, CH3COOꢁ, SO4
Fig. 2. HPLC of (a) Compound 1 (1.5
m
mol/L); (b) Fluorescein (3
mmol/L); (c) the reaction product of 1 (1.5
mmol/L) with NaHS (45 mmol/L) after incubation of them for 20 min
in CH3CN/Water (6:4) solution; (d) the reaction product of 1 (1.5
m
mol/L) with NaHS (45 mol/L) after incubation of them for 40 min in CH3CN/Water (6:4) solution.
m
Please cite this article in press as: H.-Y. Liu, et al., Fluorescein-derived fluorescent probe for cellular hydrogen sulfide imaging, Chin.
Chem. Lett. (2014), http://dx.doi.org/10.1016/j.cclet.2014.05.010

G Model
CCLET 2988 1–5
4
H.-Y. Liu et al. / Chinese Chemical Letters xxx (2014) xxx–xxx
Fig. 3. Fluorescence responses of 10
m
mol/L 1 to various analytes in aqueous solution. Excitation at 450 nm. Bars represent the final fluorescence intensity of 1 with 1 mmol/L
analytes over the original emission of free 1. (1) Brꢁ; (2) Clꢁ; (3) ClOꢁ; (4) CNꢁ; (5) CO32ꢁ; (6) Cystein; (7) NaHS; (8) Fꢁ; (9) GSH; (10) H2PO4ꢁ; (11) HCO3ꢁ; (12) Homo-Cys;
(13) HP2O73ꢁ; (14) HPO42ꢁ; (15) HSO3ꢁ; (16) HSO4ꢁ; (17) Iꢁ; (18) ascorbic acid; (19) N3ꢁ; (20) citric acid; (21) hydrogen citrate; (22) dihydrogen citric acid; (23) No; (24)
NO2ꢁ; (25) NO3ꢁ; (26) OAcꢁ; (27) P2O74ꢁ; (28) PO43ꢁ; (29) S2O42ꢁ; (30) S2O52ꢁ; (31) S2O82ꢁ; (32) SCNꢁ; (33) SO42ꢁ; (34) SO32ꢁ; (35) S2O32ꢁ; (36) N-acetyl cysteine.
Fig. 4. Fluorescence images of HeLa cells incubated with 5
mmol/L 1 and H2S. Cells treated with 1 (a) in the absence and (b) presence of 100 mmol/L of H2S incubated for
30 min; (c) bright field; (d) merged images of (b) and bright field. Scale bars = 10
mmol/L.
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
HSO4ꢁ, citrate, hydrogen citrate, dihydrogen citrate, ascorbic acid,
Chinese Academy of Sciences, and State Key Laboratory of Fine
Chemicals of China (No. KF1105).
195
196
L
-cysteine, homocysteine, L-glutathione and N-acetyl-L-cysteine
produced only a nominal change in the fluorescence spectra of 1.
Therefore the probe 1 has a very high selectivity for H2S.
We next tested the ability of 1 to be used to visualize H2S in live
Appendix A. Supplementary data
197
cells. HeLa cells were incubated with 1 (5
exhibited no fluorescence (Fig. 4a). Then the cells were incubated
with 100 mol/L NaHS, a concentration of H2S comparable with
m
mol/L) for 30 min and
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.cclet.2014.05.01-
0.
198
199
200
m
physiological H2S levels, and after 30 min they displayed enhanced
green fluorescence (Fig. 4b). The cytotoxicity of 1 was examined
toward HeLa cells by a MTT assay (Fig. S11 in Supporting
information). The results showed that 95% HeLa cells survived
after 12 h (5 mmol/L 1 incubation), and after 24 h the cell viability
remained at ꢂ90%, demonstrating that 1 was of low toxicity
toward cultured cell lines. These experiments indicate that 1 can
act as a fluorescent probe to detect H2S in living cells.
References
201
[1] H. Kimura, Hydrogen sulfide: its production, release and functions, Amino Acids
41 (2011) 113–121.
[2] L. Li, P. Rose, P.K. Moore, Hydrogen sulfide and cell signaling, Annu. Rev. Phar-
macol. Toxicol. 51 (2011) 169–187.
[3] R.A. Dombkowski, M.J. Russell, K.R. Olson, Hydrogen sulfide as an endogenous
regulator of vascular smooth muscle tone in trout, Am. J. Physiol. Regul. Integr.
Comp. Physiol. 286 (2004) R678–R685.
[4] Y. Kaneko, Y. Kimura, H. Kimura, I. Niki, L-Cysteine inhibits insulin release from the
pancreatic b-cell: possible involvement of metabolic production of hydrogen
sulfide, a novel gasotransmitter, Diabetes 55 (2006) 1391–1397.
[5] R.C.O. Zanardo, V. Brancaleone, E. Distrutti, et al., Hydrogen sulfide is an
endogenous modulator of leukocyte-mediated inflammation, FASEB J. 20
(2006) 2118–2120.
[6] K. Eto, T. Asada, K. Arima, T. Makifuchi, H. Kimura, Brain hydrogen sulfide is
severely decreased in Alzheimer’s disease, Biochem. Biophys. Res. Commun. 293
(2002) 1485–1488.
[7] P. Kamoun, M.C. Belardinelli, A. Chabli, K. Lallouchi, B. Chadefaux-Vekemans,
Endogenous hydrogen sulfide overproduction in Down syndrome, Am. J. Med.
Genet. A 116A (2003) 310–311.
[8] W. Yang, G. Yang, X. Jia, L. Wu, R. Wang, Activation of KATP channels by H2S in rat
insulin-secreting cells and the underlying mechanisms, J. Physiol. 569 (2005)
519–531.
[9] S. Fiorucci, E. Antonelli, A. Mencarelli, et al., The third gas: H2S regulates perfusion
pressure in both the isolated and perfused normal rat liver and in cirrhosis,
Hepatology 42 (2005) 539–548.
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
180
4. Conclusion
181
182
183
184
185
186
187
188
189
190
In conclusion, we have reported a fluorescein-derived fluores-
cent probe 1 for H2S based on the thiolysis of dinitrophenyl ether.
Due to rapid conversion to the fluorescent species of fluorescein in
its quinoid form, a large fluorescence increase is obtained with
emission centered at 525 nm in aqueous solution. The probe has a
high selectivity for H2S over competitive analytes. This probe is
applicable to H2S detection in live cell imaging. The successful
application of our probe to detect cellular H2S will help to study the
biological role of H2S and encourage the appearance of new H2S
probes suitable for cell imaging.
191
Acknowledgments
[10] C. Szabo, Hydrogen sulphide and its therapeutic potential, Nat. Rev. Drug Discov. 6
(2007) 917–935.
[11] H. Peng, W. Chen, S. Burroughs, B. Wang, Recent advances in fluorescent probes
for the detection of hydrogen sulfide, Curr. Org. Chem. 17 (2013) 641–653.
[12] A.R. Lippert, Designing reaction-based fluorescent probes for selective hydrogen
sulfide detection, J. Inorg. Biochem. 133 (2014) 136–142.
192 Q2
193
We thank financial supports from the National Natural Science
Foundation of China (No. 21276251), Ministry of Human Resources
194 Q3 and Social Security of PRC, the 100 talents program funded by
Please cite this article in press as: H.-Y. Liu, et al., Fluorescein-derived fluorescent probe for cellular hydrogen sulfide imaging, Chin.
Chem. Lett. (2014), http://dx.doi.org/10.1016/j.cclet.2014.05.010

G Model
CCLET 2988 1–5
H.-Y. Liu et al. / Chinese Chemical Letters xxx (2014) xxx–xxx
5
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
[13] V.S. Lin, C.J. Chang, Fluorescent probes for sensing and imaging biological hydro-
gen sulfide, Curr. Opin. Chem. Biol. 16 (2012) 595–601.
[14] N. Kumar, V. Bhalla, M. Kumar, Recent developments of fluorescent probes for the
detection of gasotransmitters (NO, CO and H2S), Coord. Chem. Rev. 257 (2013)
2335–2347.
[15] T. Chen, Y. Zheng, Z. Xu, et al., A red emission fluorescent probe for hydrogen
sulfide and its application in living cells imaging, Tetrahedron Lett. 54 (2013)
2980–2982.
[16] Y. Zheng, M. Zhao, Q. Qiao, et al., A near-infrared fluorescent probe for hydrogen
sulfide in living cells, Dyes Pigments 98 (2013) 367–371.
[17] Y.H. Li, J.F. Yang, C.H. Liu, J.S. Li, R.H. Yang, Colorimetric and fluorescent detection
of biological thiols in aqueous solution, Chin. Chem. Lett. 24 (2013) 96–98.
[18] Q. Liu, L. Xue, D.J. Zhu, G.P. Li, H. Jiang, Highly selective two-photon fluores-
cent probe for imaging of nitric oxide in living cells, Chin. Chem. Lett. 25
(2014) 19–23.
[19] S. Wu, Y.J. Wei, Y.B. Wang, et al., Ratiometric and selective two-photon fluorescent
probe based on PET-ICT for imaging Zn2+ in living cells and tissues, Chin. Chem.
Lett. 25 (2014) 93–98.
[20] X.H. Yang, S. Sun, P. Liu, et al., A novel fluorescent detection for PDGF-BB based on
dsDNA-templated copper nanoparticles, Chin. Chem. Lett. 25 (2014) 9–14.
[21] H. Zheng, X.Q. Zhan, Q.N. Bian, X.J. Zhang, Advances in modifying fluorescein and
rhodamine fluorophores as fluorescent chemosensors, Chem. Commun. 49 (2013)
429–447.
[22] X. Chen, T. Pradhan, F. Wang, J.S. Kim, J. Yoon, Fluorescent chemosensors based on 256
spiroring-opening of xanthenes and related derivatives, Chem. Rev. 112 (2011) 257
1910–1956.
258
[23] G.M. van Dam, G. Themelis, L.M.A. Crane, et al., Intraoperative tumor-specific 259
fluorescence imaging in ovarian cancer by folate receptor-[alpha] targeting: first 260
in-human results, Nat. Med. 17 (2011) 1315–1319.
261
[24] V. Dujols, F. Ford, A.W. Czarnik, A long-wavelength fluorescent chemodosimeter 262
selective for Cu(II) ion in water, J. Am. Chem. Soc. 119 (1997) 7386–7387.
263
[25] Z.X. Han, B.S. Zhu, T.L. Wu, et al., A fluorescent probe for Hg2+ sensing in solutions 264
and living cells with a wide working pH range, Chin. Chem. Lett. 25 (2014) 73–76. 265
[26] C. Liu, J. Pan, S. Li, et al., Capture and visualization of hydrogen sulfide by a 266
fluorescent probe, Angew. Chem. Int. Ed. 50 (2011) 10327–10329.
267
[27] J. Zhang, Y.Q. Sun, J. Liu, Y. Shi, W. Guo, A fluorescent probe for the biological 268
signaling molecule H2S based on a specific H2S trap group, Chem. Commun. 49 269
(2013) 11305–11307.
[28] C. Wei, Q. Zhu, W. Liu, et al., NBD-based colorimetric and fluorescent turn-on 271
probes for hydrogen sulfide, Org. Biomol. Chem. 12 (2014) 479–485.
[29] C. Liu, B. Peng, S. Li, et al., Reaction based fluorescent probes for hydrogen sulfide, 273
Org. Lett. 14 (2012) 2184–2187.
[30] T. Liu, Z. Xu, D.R. Spring, J. Cui, A lysosome-targetable fluorescent probe for 275
imaging hydrogen sulfide in living cells, Org. Lett. 15 (2013) 2310–2313.
[31] T. Liu, X. Zhang, Q. Qiao, et al., A two-photon fluorescent probe for imaging 277
hydrogen sulfide in living cells, Dyes Pigments 99 (2013) 537–542.
270
272
274
276
278
Please cite this article in press as: H.-Y. Liu, et al., Fluorescein-derived fluorescent probe for cellular hydrogen sulfide imaging, Chin.
Chem. Lett. (2014), http://dx.doi.org/10.1016/j.cclet.2014.05.010