An AIE and ESIPT based kinetically resolved fluorescent probe for biothiols

Article abstract of DOI:10.1039/c5tc03272e

A new aggregation-induced emission and excited-state intramolecular proton transfer based fluorescent probe, containing a salicylaldazine moiety as a platform, displayed an excellent light-up ratio and a large Stokes shift for the detection of biothiols (

Full text of DOI:10.1039/c5tc03272e

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An AIE and ESIPT based kinetically resolved
fluorescent probe for biothiols†
Cite this:DOI: 10.1039/c5tc03272e
Lei Cui,ab Yeonju Baek,a Songyi Lee,a Nahyun Kwona and Juyoung Yoon*a
A new aggregation-induced emission and excited-state intramolecular proton transfer based fluorescent
probe, containing a salicylaldazine moiety as a platform, displayed an excellent light-up ratio and a large
Stokes shift for the detection of biothiols (cysteine, homocysteine, and glutathione). The salicylaldazine
based fluorescent probe showed high selectivity, and sensitivity for biothiols. With the aid of different
reactivities, a kinetically resolved method was successfully applied to distinguish different biothiols both
in solution and cells.
Received 11th October 2015,
Accepted 19th November 2015
DOI: 10.1039/c5tc03272e
www.rsc.org/MaterialsC
fluorophore has no emission in a low concentration solution
but has strong emission in the aggregate state.12 If the designed
Introduction
Biothiols such as cysteine (Cys), homocysteine (Hcy), and glutathione probe reacts with biothiols, for example, via Michael addition,
(GSH) are very important small molecules and play important roles the addition product will affect the solubility of the molecule in
in various physiological processes.1 In living systems, Cys and Hcy water, which will further change the fluorescence intensity. AIE
are vital molecules for promoting cell and tissue growth. GSH as a and ESIPT-based platforms have shown ever-increasing interest
regulator keeps the redox balance.2 For example, the oxidized state of in recent years.12,13
GSH is glutathione (GSSG), which plays critical roles in keeping
Herein, we report a new kinetically-resolved fluorescent probe,
cellular homeostasis and various physiological functions.3 The level which can efficiently discriminate Cys, GSH, Hcy, and H2S. This
of these biothiols in the body is also closely related to various probe is based on the classic ‘‘AIE + ESIPT’’ platform salicylaldazine
diseases including cancer, AIDS, and liver damage.4 Cys is an import- with the acrylate moiety (AIE-S) as the receptor and fluorescence
ant amino acid that plays an important role in protein function. quencher. When the hydroxyl group in the salicylaldazine dye is
A lower level of Cys in the body can cause various diseases such as protected, the excited-state proton transfer from the hydroxyl group
slow growth, hair depigmentation, edema, lethargy, liver damage, (proton donor) to nitrogen (proton acceptor) will be blocked, and
and muscle/fat loss.5 In this regard, developing sensitive and con- AIE-S will show a weak fluorescence emission. Interestingly, the
venient methods for the detection of biothiols is very important.
probe AIE-S showed a significant difference in its reaction kinetics
Fluorescent probes have been actively investigated as an with biothiols, offering a unique method to identify Cys from other
effective technique for the detection of bioactive species.6 As biothiols. After the probe AIE-S was treated with biothiols for
described above, owing to the biological importance of these 15 min, only Cys induced a strong fluorescence signal. After
biothiols, various thiol-responsive fluorescent probes have been 40 min, strong fluorescence emissions were observed with both
developed.7 The mechanism of reported fluorescent probes for Cys and GSH but not with Hcy or H2S. Moreover, all biothiols
the detection of biothiols falls into the following categories: induced similar fluorescence intensities about 4 h later.
Michael addition, cyclization reaction with aldehyde, deprotection
of sulphonamide and sulfonate esters, and disulfide exchange
Experimental
Materials
reaction.8 Even though there have been some successful examples
to discriminate Cys, HCy, and GSH,9–11 designing a selective
fluorescent probe for one of these three biothiols is still a
challenging task. An aggregation-induced emission (AIE) based
2-Hydroxybenzaldehyde, hydrazine monohydrate, cesium carbonate,
and anhydrous dimethylformamide were all purchased from
Sigma-Aldrich. All other chemicals and solvent were purchased
from Daejung, Korea.
a Department of Chemistry and Nano Science, Ewha Womans University,
Seoul 120-750, Republic of Korea. E-mail: jyoon@ewha.ac.kr
b College of Science, School of Environment and Architecture,
Equipment and methods
University of Shanghai for Science and Technology (USST), Shanghai, China
† Electronic supplementary information (ESI) available: Experimental, synthetic,
spectroscopic, and bioassay details. See DOI: 10.1039/c5tc03272e
UV-visible absorption spectra were obtained using a UV-visible
spectrometer (Scinco 3000 spectrophotometer). Fluorescence spectra
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were measured using a RF-5301/PC (Shimadzu) fluorescence for one night before cell imaging experiments. For the living
spectrophotometer at 25 1C. 1H and 13C spectra were measured cell imaging experiment of a probe, the cells were incubated with
using a Bruker ARX 300 NMR spectrometer. The molecular 5 mM probe AIE-S (with 1% DMSO, v/v) for 20 min at 37 1C and
mass was acquired using ion trap time-of-flight mass spectro- washed twice with prewarmed PBS and then imaged immedi-
metry (MS-TOF). The pH values of buffers were adjusted using a ately. For imaging of biothiols using probe AIE-S treated experi-
Sartorius PB-10 basic pH meter. Deionized water was used to ments, HeLa cells were pretreated with the 5 mM probe for 20 min
prepare all aqueous solutions.
at 37 1C, washed twice with prewarmed PBS, and then incubated
with 10 mM biothiols at 37 1C. Cell imaging was then performed
after washing cells with PBS buffer.
Synthesis and characterization
Synthesis of compound A. To a solution of 2-hydroxy-4-
methoxybenzaldehyde (300 mg, 1.97 mmol) in ethanol (20 mL),
hydrazine monohydrate (50 mg, 48 mL, 0.98 mmol) was added.
Then, the mixture was heated to reflux for 4 h. The precipitate
was collected and washed twice with ethanol. The pure product
A was obtained as a yellow powder (223 mg, 75% yield).
1H NMR (CDCl3, 300 MHz): d 11.77 (s, 2H), 8.60 (s, 2H), 7.25
(d, J = 6.0 Hz, 2H), 6.56–6.52 (m, 4H), 3.86 (s, 6H). 13C NMR
(CDCl3, 75 MHz): d 163.86, 162.82, 161.76, 133.50, 111.10, 107.50,
101.20, 55.51.
Synthesis of compound AIE-S. To a solution of compound
A (160 mg, 0.53 mmol) in anhydrous DMF (5 mL), cesium
carbonate (347.2 mg, 1.07 mmol) was added and stirred at
room temperature (rt) for 30 min. Acryloyl chloride (192.9 mg,
2.13 mmol) was added slowly at 0 1C using a syringe. After
stirring for 30 min, the solution was warmed to rt for 3 h. Then,
20 mL of water was added to the reaction solution and stirred
for 10 min. The obtained precipitate was filtered and washed
twice with H2O before drying under vacuum. Product B was
obtained as a light yellow powder (200 mg, 92% yield). 1H NMR
(CDCl3, 300 MHz): d 8.64 (s, 2H), 8.03 (d, J = 9.0 Hz, 2H), 6.89
(dd, J1 = 2.4 Hz, J2 = 9.0 Hz, 2H), 6.73 (d, J = 17.4 Hz, 2H), 6.39 (q,
Results and discussion
Probe design and synthesis
The probe AIE-S was designed based on salicylaldazine, in which
the hydroxyl group is protected by the acryloyl group. When AIE-S
was treated with biothiols, two-step reactions were involved, as
shown in Scheme 1. The thiol moiety in Cys first reacts with the
acryloyl group via Michael addition, followed by a spontaneous
intramolecular cyclization reaction to release the salicylaldazine
dye. After the deprotection of the hydroxyl group, the salicylaldazine
dye can restore the intermolecular hydrogen bonds, which would
further light up a long-wavelength emission. A similar reaction
mechanism has been reported before.14 The synthetic procedure
of the probe AIE-S is illustrated in Scheme 2. Fluorophore 2 was
obtained by the condensation reaction between 2-hydroxy-4-
methoxybenzaldehyde 1 and hydrazine monohydrate in 75%
yield. Then, salicylaldazine dye 2 reacted with acryloyl chloride in
anhydrous DMF with Cs2CO3 as the base to afford the probe AIE-S
in 92% yield. The structures were confirmed by H NMR, 13C
NMR, and HRMS. The detailed data can be found in the ESI.†
1
J1 = 10.5 Hz, J2 = 17.4 Hz, 2H), 6.09 (dd, J1 = 1.2 Hz, J2 = 10.2 Hz, Optical properties
2H), 3.87 (s, 6H). 13C NMR (CDCl3, 75 MHz): d 164.1, 162.6,
The optical spectra of the probe AIE-S and salicylaldazine dye 2
156.6, 151.4, 133.3, 129.5, 127.5, 119.1, 113.0, 108.1, 55.7.
HRMS(ESI): m/z [M + 1]+ calcd for C22H20N2O6: 409.1321; found:
409.1364.
were recorded in PBS buffer with 1% DMSO at room tempera-
ture. As shown in Fig. 1, AIE-S shows a maximum absorption at
340 nm, and the fluorescence is quenched upon excitation at
340 nm. In contrast, salicylaldazine dye 2 displayed a strong
fluorescence emission at a wavelength of 505 nm. This observ-
able change guarantees that the probe AIE-S will display high
sensitivity to biothiols both in vivo and in vitro.
Solutions preparation and optical measurements
The optical spectra of the probe AIE-S and the compound were
measured in a mixture of DMSO–H2O (v/v = 1/99) at an excita-
tion wavelength of 340 nm. The stock solution of analytes
including biothiols Cys, Hcy, GSH, and other amino acids such
as Phe, Gln, Trp, Thr, Met, Glu, Ile, Gly, Tyr, Arg, Ser, Ala, Asp,
Leu, and His (1 mM of each) as well as anions FÀ, ClÀ, BrÀ, IÀ,
NO3À, NO2À, SCNÀ, CO32À, SO42À, SO32À, HSÀ and S2À (50 mM
of each, sodium salts) were prepared in ultrapure water. The
stock solution of probe 1 (1 mM) was prepared in HPLC grade
DMSO. UV-vis or fluorescence spectra were recorded upon the
addition of various analytes.
Cell imaging experiments
HeLa cells were cultured in Dulbecco’s Modified Eagle’s Medium
(DMEM) supplemented with 10% FBS (Fatal Bovine Serum),
with 100 mg mLÀ1 penicillin and 100 mg mLÀ1 streptomycin to
prevent bacterial contamination, in a 5% CO2, water saturated
Scheme 1 A plausible mechanism of the response of the probe AIE-S
incubator at 37 1C, and then seeded in a 12-well culture plate to Cys.
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Detection of biothiols
Before studying the probe AIE-S for the detection of biothiols,
the effect of pH on salicylaldazine dye 2 was examined. As shown
in Fig. S1 (ESI†), a strong fluorescence signal was observed
between pH B 4 and 8. With increasing pH value continues,
the fluorescence intensity decreased, because of the deprotona-
tion of the salicylaldazine dye’s hydroxyl group. The fluorescence
intensity is relatively stable in the pH range of 4–8 (oÆ4%). As
shown in Scheme 1, biothiols react with the probe AIE-S via
Michael addition, followed by a spontaneous intramolecular
cyclization, which induced the ester bond cleavage. Theoreti-
cally, all biothiols (Cys, Hcy, and GSH) will react with AIE-S.
As shown in Fig. 3a, there is almost no fluorescence for the
probe itself. After the addition of Cys to the probe solution for
B30 min, a significant green fluorescence signal gradually
increased at the maximum wavelength of B505 nm. In order
to get more information about the reaction, a kinetic experi-
ment was also performed. As shown in Fig. 3b, in the absence
of Cys, the fluorescence intensity did not change for B50 min,
supporting that the probe was stable enough under this con-
dition. When the probe AIE-S was mixed with Cys in PBS buffer,
a significant enhancement in the fluorescence intensity was
observed at 505 nm. In 25 min, the fluorescence intensity reached
its maximum. Two different ways of measuring the time-
dependent fluorescence kinetic spectra provided consistent data,
Scheme 2 Synthetic route for the probe AIE-S.
Fig. 1 UV-vis absorption (dashed line) and FL (solid line) spectra of AIE-S
(red) and salicylaldazine dye 2 (black) in DMSO–water (1 : 99, v/v). The
concentrations of AIE-S and salicylaldazine dye were 10 mM and 30 mM,
respectively.
The optical spectra of salicylaldazine dye 2 were recorded in a
DMSO/H2O mixture with different DMSO fractions ( fd), showing
the relationship between the solvent polarity and the extent of
salicylaldazine dye aggregation. As shown in Fig. 2, the fluores-
cence was almost completely quenched in pure DMSO solution.
As the ratio of DMSO in solution gradually decreases, the fluores-
cence intensity increased slightly with a maximum emission at
the wavelength 505 nm from fd = 100 to 20 (v/v). Between fd = 80
and 1 (v/v), the fluorescence intensity increased dramatically from
23 to 578 and is consistent with the phenomenon of AIE.
Fig. 3 (a) Fluorescence spectral changes of the probe AIE-S (10 mM) upon
addition of Cys (50 mM) in PBS buffer (10 mM, pH 7.4) with 1% DMSO at
25 1C; (b) time-dependence of the fluorescence kinetic spectra of the
probe AIE-S (10 mM) upon addition of Cys (0, 20, and 50 mM) in DMSO-PBS
buffer (10 mM, pH 7.4, 1 : 99, v/v) at 25 1C. All the reactions were monitored
every 0.05 s at 505 nm. lex = 340 nm.
Fig. 2 Plot of relative FL intensity (I/I0) versus the solvent composition of
the DMSO/water mixture of salicylaldazine dye 2.
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(Cys, GSH, and Hcy) (Fig. S2, ESI†). In contrast, Na2S cannot
induce the second intermolecular cyclization reaction; therefore,
there was not any significant fluorescence change. The huge
kinetic difference between Cys and Hcy can be attributed to the
kinetic rate of the intramolecular adduct/cyclization reactions.
The seven-membered ring formation by Cys is a kinetically
favored intramolecular cyclization reaction compared to the
eight-membered ring by Hcy. For GSH, the product of the first
step is the Michael adduct.
Further kinetic experiments of GSH showed that if the
concentration of GSH was decreased from 100 mM to 20 mM,
the fluorescence enhancement was delayed from 20 to 40 min
(Fig. S3, ESI†). Therefore, the kinetically resolved AIE and ESIPT
based AIE-S probe is sensitive enough to discriminate different
biothiols especially in the case of low concentration.
Fig. 4 Fluorescence spectra of 10 mM AIE-S in the presence of different
amounts of Cys (from 0 to 16 mM) in PBS buffer (10 mM, pH = 7.4,
1% DMSO), lex = 340 nm. Inset: The fluorescence intensity at 505 nm as
a function of Cys concentration.
Next, the selectivity of the probe AIE-S to different amino
acids was investigated in water solution with 1% DMSO over
25 min. (Fig. 6). The blank solution of AIE-S showed almost no
fluorescence. Upon the addition of Cys, a selective fluorescence
enhancement was observed. In contrast, Hcy and GSH induced
only a slight change in their fluorescence emissions. In addi-
tion, there was not any significant change upon the addition of
other amino acids. Other common metal cations and anions
indicating that the probe AIE-S could be used as a highly
sensitive OFF–ON probe for Cys in the PBS buffer with 1% DMSO
at room temperature.
A linear relationship was observed between I505 and [Cys] in
the range of 1–16 mM (Fig. 4). The relationship between the
emission at 340 nm and the Cys concentration was calculated
as y = 7.59 + 5.92 Â x, where y is the fluorescence intensity at
340 nm and x is the concentration of Cys. The linear range of
the method was in the concentration range of 1–20 mM Cys with
a correlation coefficient (R2) of 0.985.
Next, the time-dependent fluorescence kinetic spectra of
AIE-S to Hcy, GSH, and Na2S were also tested (Fig. 5). Surprisingly,
in 20 min, only the one treated with Cys reached the plateau. In
contrast, negligible fluorescence intensity changes were observed
for Hcy, GSH, and Na2S. The fluorescence intensity response of
AIE-S with GSH slightly decreased in 20 min, then increased
quickly, and reached almost the same fluorescence intensity as
Cys after 50 min. For Hcy, the fluorescence intensity increased
slowly for 50 min, and only a quarter of the fluorescence intensity
was observed compared to that with Cys. After 4 h, similar
fluorescence intensities were observed for all three biothiols
were also tested (Fig. S4 and S5, ESI†). Potential interfering
2À
anion species such as ClÀ, BrÀ, IÀ, NO3À, NO2À, AcOÀ, C2O4
,
PO43À, CO32À, SO42À, SO32À, S2À, HSÀ, SCNÀ, IO4À, and ClO4
À
were also added to the probe AIE-S solution over 20 min. None
of these anions could induce any significant fluorescence
changes, indicating that the probe AIE-S is a highly selective
fluorescent probe for Cys.
Prior to the cell imaging experiments, the cytotoxicity of the
probe AIE-S was first tested by MTT assays (Fig. S6, ESI†). The
cell viability test did not show any difference between the cells
treated with AIE-S and untreated cells, indicating that the probe
AIE-S would not interfere with the physiology or proliferation of
the cells under the tested concentration range.
The probe AIE-S was then used to image biothiols in living
cells. As shown in Fig. 7, when HeLa cells were treated with only
AIE-S for 20 min, no fluorescence was observed. When HeLa
cells were incubated with the probe for 20 min and then treated
Fig. 5 Time-dependent fluorescence kinetic spectra of the probe AIE-S
(10 mM) upon addition of Cys, GSH, Hcy, and Na2S (100 mM) in DMSO–PBS
buffer (10 mM, pH 7.4, 1 : 99, v/v) at 25 1C. All the reactions were monitored
every 0.02 s at 505 nm. lex = 340 nm.
Fig. 6 Selectivity of AIE-S towards Cys. Fluorescence response of AIE-S
(10 mM) at 505 nm in the presence of different amino acids (1 mM) in a PBS/
DMSO mixture (99 : 1, v/v) at an excitation wavelength of 340 nm.
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Cys over GSH and Hcy. More specifically, when the probe AIE-S
was treated with biothiols for 15 min, only Cys induced a strong
fluorescence signal. After 40 min, strong fluorescence emis-
sions were observed with both Cys and GSH but not with Hcy or
H2S. The turn-on emissions of AIE-S by biothiols allowed us to
identify these three biothiols by the kinetic process. Finally, the
probe AIE-S was also used to image biothiols in living cells.
Acknowledgements
The authors acknowledge a grant from the National Creative
Research Initiative programs of the National Research Founda-
tion of Korea (NRF) funded by the Korean government (MSIP)
(No. 2012R1A3A2048814). Mass spectral data were obtained
from the Korea Basic Science Institute (Daegu) on a Jeol JMS
700 high resolution mass spectrometer.
Fig. 7 Imaging of biothiols using the probe AIE-S in living HeLa cells. Top:
bright field images. (a) HeLa cells were incubated with the probe AIE-S
(5 mM) for 20 min. (d), (g), and (j) HeLa cells were pre-incubated with the
probe AIE-S for 20 min and then treated with Cys, GSH, and Hcy (10 mM)
for 20 min. Middle: (b), (e), (h), and (k) are the fluorescence images of (a),
(d), (g), and (j), respectively. Bottom: (c), (f), (i), and (l) are the overlap images
of bright field and fluorescence images of (a), (d), (g), and (j), respectively.
References
1 J. B. Schulz, J. Lindenau, J. Seyfried and J. Dichgans,
Eur. J. Biochem., 2000, 267, 4904.
2 D. Trachootham, W. Lu, M. A. Ogasawara, N. R.-D. Valle and
P. Huang, Antioxid. Redox Signaling, 2008, 10, 1343.
3 M. L. Circu and T. Yee Aw, Free Radical Res., 2008, 42, 689.
4 (a) A. Basu, A. Bhattacharjee, A. Samanta and S. Bhattacharya,
Environ. Toxicol. Pharmacol., 2015, 40, 747; (b) F. Liu, Y. Fang,
Y. Chen and J. Liu, J. Phys. Chem. B, 2011, 115, 9898;
(c) Y. Fang, F. Liu, R. Emre and J. Liu, J. Phys. Chem. B,
2013, 117, 2878.
Fig. 8 Imaging of biothiols using the probe AIE-S in living HeLa cells. Top:
bright field images. (a) HeLa cells were incubated with the probe AIE-S
(5 mM) for 20 min. (d), (g), and (J) HeLa cells were pre-incubated with the
probe AIE-S for 40 min and then treated with Cys, GSH, and Hcy (10 mM)
for 20 min. Middle: (b), (e), (h), and (k) are the fluorescence images of (a), (d),
(g), and (J), respectively. Bottom: (c), (f), (i), and (l) are the overlap images of
bright field and fluorescence images of (a), (d), (g), and (J), respectively.
5 M. C. Miniaci, C. Irace, A. Capuozzo, M. Piccolo, A. D.
Pascale, A. Russo, P. Lippiello, F. Lepre, G. Russo and
R. Santamaria, J. Cell. Biochem., 2015, 116, 1982.
6 (a) J. Yin, Y. Hu and J. Yoon, Chem. Soc. Rev., 2015, 44, 4619;
(b) X. Zhou, S. Lee, Z. Xu and J. Yoon, Chem. Rev., 2015,
115, 7944; (c) L. Cui, Z. Peng, C. Ji, J. Huang, D. Huang,
J. Ma, S. Zhang, X. Qian and Y. Xu, Chem. Commun., 2014,
50, 1485; (d) S. Lee, K. K. Y. Yuen, K. A. Jolliffe and J. Yoon,
Chem. Soc. Rev., 2015, 44, 1749; (e) Y. Tang, D. Lee, J. Wang,
G. Li, W. Lin and J. Yoon, Chem. Soc. Rev., 2015, 44, 5003;
( f ) Q. Xu, C. H. Heo, G. Kim, H. W. Lee, H. M. Kim and
J. Yoon, Angew. Chem., Int. Ed., 2015, 54, 4890.
with Cys (10 mM) for 20 min, strong green fluorescence was
clearly observed (e). In contrast, the treatment with GSH or HCy
for 20 min induced only very weak green fluorescence. As des-
cribed in the previous experiment, the GSH would have a similar
fluorescence intensity for B40 min. Therefore, the reaction time
was extended to 40 min to that of the probe treated HeLa cells
with biothiols. In this experiment, similar results were obtained
to those above except for GSH. When GSH was added to the
probe pretreated with Hela cells for 40 min, a strong green
fluorescence was detected, indicating that after incubation for
40 min, both Cys and GSH showed a strong green fluorescence
but Hcy did not. These results are extremely consistent with the
previous kinetic experiment (Fig. 8).
7 (a) H. S. Jung, X. Chen, J. S. Kim and J. Yoon, Chem.
Soc. Rev., 2013, 42, 6019; (b) C. Yin, F. Huo, J. Zhang,
´
´˜
R. Martınez-Manez, Y. Yang, H. Lv and S. Li, Chem. Soc.
Rev., 2013, 42, 6032; (c) L. Y. Niu, Y. Z. Chen, H. R. Zheng,
L. Z. Wu, C. H. Tung and Q. Z. Yang, Chem. Soc. Rev., 2015,
44, 6143; (d) M. Lan, J. Wu, H. Zhang, W. Zhang, X. Zhuang
and P. Wang, Sens. Actuators, B, 2011, 156, 332; (e) M. Lan,
J. Zhang, Y.-S. Chui, H. Wang, Q. Yang, X. Zhu, H. Wei,
W. Liu, J. Ge, P. Wang, X. Chen, C.-S. Lee and W. Zhang,
J. Mater. Chem. B, 2015, 3, 127; ( f ) S. Zhao, M. Lan, X. Zhu,
H. Xue, T.-W. Ng, X. Meng, C.-S. Lee, P. Wang and W. Zhang,
ACS Appl. Mater. Interfaces, 2015, 7, 17054.
Conclusions
In conclusion, we designed and synthesized a new AIE and
ESIPT-based fluorogenic dye, displaying signal amplifications
in the presence of biothiols. AIE-S showed a high selectivity for
8 (a) X. Chen, Y. Zhou, X. Peng and J. Yoon, Chem. Soc. Rev.,
2010, 39, 2120; (b) S. Kolemen, M. Is-ık, G. M. Kim, D. Kim,
This journal is ©The Royal Society of Chemistry 2015
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View Article Online
Paper
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H. Geng, M. Buyuktemiz, T. Karatas, X.-F. Zhang, Y. Dede,
J. Yoon and E. U. Akkaya, Angew. Chem., Int. Ed., 2015,
Y. Q. Sun, Y. Huo, H. Zhang, L. Wang, P. Zhang, D. Song,
Y. Shi and W. Guo, J. Am. Chem. Soc., 2014, 136, 574.
54, 5340; (c) X. Chen, S.-K. Ko, M. J. Kim, I. Shin and 11 Selected references for Hcy. (a) H. Y. Lee, Y. P. Choi, S. Kim,
J. Yoon, Chem. Commun., 2010, 46, 2751; (d) Y. Hu, C. H. Heo,
G. Kim, E. J. Jun, J. Yin, H. M. Kim and J. Yoon, Anal. Chem.,
2015, 87, 3308.
9 Selected references for GSH. (a) J. Yin, Y. Kwon, D. Kim,
D. Lee, G. Kim, Y. Hu, J.-H. Ryu and J. Yoon, J. Am. Chem.
Soc., 2014, 136, 5351; (b) S. Y. Lim, K. H. Hong, D. I. Kim,
H. Kwon and H. J. Kim, J. Am. Chem. Soc., 2014, 136, 7018;
(c) J. Liu, Y. Sun, H. Zhang, Y. Huo, Y. Shi and W. Guo,
Chem. Sci., 2014, 5, 3183; (d) F. Wang, L. Zhou, C. Zhao,
T. Yoon, Z. Guo, S. Lee, K. M. K. Swamy, G. Kim, J. Y. Lee,
I. Shin and J. Yoon, Chem. Commun., 2014, 50, 6967–6969;
(b) H. Peng, K. Wang, C. Dai, S. Williamson and B. Wang,
Chem. Commun., 2014, 50, 13668; (c) A. Barve, M. Lowry,
J. O. Escobedo, K. T. Huynh, L. Hakuna and R. M. Strongin,
Chem. Commun., 2014, 50, 8219; (d) K. S. Lee, T. K. Kim,
J. H. Lee, H. J. Kim and J. I. Hong, Chem. Commun., 2008,
6173; (e) J. Zhang, X. Jiang, X. Shao, J. Zhao, Y. Su, D. Xi,
H. Yu, S. Yue, L. Xiao and W. Zhao, RSC Adv., 2014, 4, 54080.
R. Wang, Q. Fei, S. Luo, Z. Guo, H. Tian and W. Zhu, Chem. 12 (a) R. Hu, N. L. C. Leung and B. Z. Tang, Chem. Soc. Rev.,
Sci., 2015, 6, 2584; (e) L. Y. Niu, Y. S. Guan, Y. Z. Chen,
L. Z. Wu, C. H. Tung and Q. Z. Yang, J. Am. Chem. Soc., 2012,
134, 18928; ( f ) Y. Zhang, X. Shao, Y. Wang, F. Pan, R. Kang,
F. Peng, Z. Huang, W. Zhang and W. Zhao, Chem. Commun.,
2014, 43, 4494; (b) R. T. K. Kwok, C. W. T. Leung, J. W. Y.
Lam and B. Z. Tang, Chem. Soc. Rev., 2015, 44, 4228;
(c) J. Zhao, S. Ji, Y. Chen, H. Guo and P. Yang, Phys. Chem.
Chem. Phys., 2012, 14, 8803.
2015, 51, 4245; (g) J. Yin, Y. Kwon, D. Kim, D. Lee, G. Kim, 13 (a) M. Gao, Q. Hu, G. Feng, B. Z. Tang and B. Liu, J. Mater.
Y. Hu, J.-H. Ryu and J. Yoon, Nat. Protoc., 2015, 10, 1742.
10 Selected references for Cys. (a) Z. Guo, S. Nam, S. Park and
J. Yoon, Chem. Sci., 2012, 3, 2760; (b) X. Yang, Y. Guo and
R. M. Strongin, Angew. Chem., Int. Ed., 2011, 50, 10690;
(c) M. Isik, T. Ozdemir, I. S. Turan, S. Kolemen and
E. U. Akkaya, Org. Lett., 2013, 15, 216; (d) H. S. Jung,
T. Pradhan, J. H. Han, K. J. Heo, J. H. Lee, C. Kang and
J. S. Kim, Biomaterials, 2012, 33, 8495; (e) F. Wang, J. An,
L. Zhang and C. Zhao, RSC Adv., 2014, 4, 53437;
( f ) D. H. Ma, D. Kim, T. Akisawa, K. H. Lee, K. T. Kim
and K. H. Ahn, Chem. – Asian J., 2015, 10, 894; (g) Y. Liu,
D. Yu, S. Ding, Q. Xiao, J. Guo and G. Feng, ACS Appl. Mater.
Interfaces, 2014, 6, 17543; (h) D. Lee, G. Kim, J. Yin and
Chem. B, 2014, 2, 3438; (b) X. Lou, Y. Hong, S. Chen, C. W.
Leung, N. Zhao, B. Situ, J. W. Lam and B. Z. Tang, Sci. Rep., 2014,
4, 4272; (c) J. E. Kwon and S. Y. Park, Adv. Mater., 2011, 23, 3615;
(d) S. Park, O.-H Kwon, Y.-S. Lee, D.-J. Jang and S. Y. Park, J. Phys.
Chem. A, 2007, 111, 9649; (e) J. Cheng, Y. Li, R. Sun, J. Liu,
F. Gou, X. Zhou, H. Xiang and J. Liu, J. Mater. Chem. C, 2015,
3, 11099; ( f ) K.-I. Sakai, T. Ishikawa and T. Akutagawa, J. Mater.
Chem. C, 2015, 1, 7866; (g) Z. Song, R. T. Kwok, E. Zhao, Z. He,
Y. Hong, J. W. Lam, B. Liu and B. Z. Tang, ACS Appl. Mater.
Interfaces, 2014, 6, 17245; (h) M. Gao, C. K. Sim, C. W. Leung,
Q. Hu, G. Feng, F. Xu, B. Z. Tang and B. Liu, Chem. Commun.,
2014, 50, 8312; (i) V. Bhalla, S. Pramanik and M. Kumar, Chem.
Commun., 2013, 49, 877.
J. Yoon, Chem. Commun., 2015, 51, 6518; (i) A. Barve, 14 (a) C. Y. Ang, S. Y. Tan, Y. Lu, L. Bai, M. Li, P. Li, Q. Zhang,
M. Lowry, J. O. Escobedo, K. T. Huynh, L. Hakuna and
R. M. Strongin, Chem. Commun., 2014, 50, 8219; ( j) H. S.
Jung, K. C. Ko, G. H. Kim, A. R. Lee, Y. C. Na, C. Kang,
J. Y. Lee and J. S. Kim, Org. Lett., 2011, 13, 1498; (k) J. Liu,
S. T. Selvan and Y. Zhao, Sci. Rep., 2014, 4, 7057; (b) D. Yu,
F. Huang, S. Ding and G. Feng, Anal. Chem., 2014, 86,
8835–8841; (c) D. Yu, Q. Zhang, S. Ding and G. Feng, RSC
Adv., 2014, 4, 46561.
J. Mater. Chem. C
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