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New Analytical Methods
Visual Assay of Glutathione in Vegetables and Fruits Using Quantum Dot Ratiometric Hybrid Probes Aimin Chen, Xiao Peng, Zaifa Pan, Kang Shao, Jing Wang, and Maohong Fan J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.8b00662 • Publication Date (Web): 04 Jun 2018 Downloaded from http://pubs.acs.org on June 4, 2018
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Figure and Table Captions Scheme 1. Schematic illustration for preparation of the ratiometric nanoprobe and the sensing mechanism for detection of GSH. Figure 1. TEM images of (A) PL emission spectra (λex = 380 nm) of (a) CdSe@SiO2–NH2, (b) NALC-CdTe QDs, and (c) CdSe@SiO2@CdTe NPs. The inset photos express the corresponding fluorescence colors under a 365 nm UV lamp. (B) CdSe@SiO2–NH2, (C) NALC-CdTe QDs, and (D) CdSe@SiO2@CdTe NPs. Figure 2. Fluorescence decay curves (λex = 405 nm, measured at the maximum of the fluorescence) of CdSe@SiO2@CdTe NPs, Before quenching (black line), Quenched by Hg2+ (red line), Restored by GSH (blue line). Figure 3. A. Effects of sample pH (0.01 M PBS) on the PL intensity ratios (I619/I535) of Hg2+ (1.2 μM) quenched CdSe@SiO2@CdTe NPs (50 μg/mL) and after restored with GSH (10 μM). B. Hg2+ concentration dependent PL quenching (red line) of CdTe QDs in ratiometric probe (50 µg/mL) and subsequent PL restoration (black line) by GSH (3 μM). All solutions were prepared in a 0.01 M PB of pH 8.0. Figure 4. Selectivity of the Hg2+ quencher ratiometric probe to some coexisting species in the PB (pH 8.0, 0.01 M), including Na+ (1000 µM), K+ (1000 µM), Mg2+ (1000 µM), Ca2+ (1000 µM), L-Cysteine (Cys, 45 µM), proline (Pro, 100 µM), Phenylalanine (Phe, 100 µM), DL-Methionine (Met, 100 µM), natural -carotene (β-C, 100 µM), Tyrosine (Tyr, 100 µM), DL-malic acid (MA, 100 µM), vitamin E acetate (VE, 100 µM), citric acid (CA, 100 µM), glucose (Glu, 100 µM) and ascorbic acid (AA, 100 µM ). The fluorescence photos were selectivity of the Hg2+ quencher
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ratiometric probe to some coexisting species in the PBS (pH 8.0, 0.01 M). Figure 5. (A) Recovery of PL spectra at different concentrations of GSH after the Hg2+ (1.2 μM) quenching CdSe@SiO2@CdTe NPs (50 µg/mL). The concentrations of GSH from bottom to top are 0, 0.1, 0.5, 1, 2, 3, 5, 7, 10, 15, 20 and 30 µM, respectively. The fluorescence photos were taken under a UV lamp under the excitation of 365 nm. (B) Plot of the PL intensity ratio (I619/535) of the Hg2+ (1.2 μM) quenching nanohybrid as a function of the GSH concentration. Table 1. Comparison of the analytical performance of the sensing systems for the detection of GSH. Table 2. Applications of the proposed method for analysis of various food samples spiked with different amounts of GSH.
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Scheme 1. Schematic illustration for preparation of the ratiometric nanoprobe and the sensing mechanism for detection of GSH
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Figure 1. TEM images of (A) PL emission spectra (λex = 380 nm) of (a) CdSe@SiO2–NH2, (b) NALC-CdTe QDs, and (c) CdSe@SiO2@CdTe NPs. The inset photos express the corresponding fluorescence colors under a 365 nm UV lamp. (B) CdSe@SiO2–NH2, (C) NALC-CdTe QDs, and (D) CdSe@SiO2@CdTe NPs.
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Figure 2. Fluorescence decay curves (λex = 405 nm, measured at the maximum of the fluorescence) of CdSe@SiO2@CdTe NPs, original probe (black line), quenched by Hg2+ (red line) and recovered by GSH (blue line).
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Figure 3. A. Effects of sample pH (0.01 M PBS) on the PL intensity ratios (I619/I535) of Hg2+ (1.2 μM) quenched CdSe@SiO2@CdTe NPs (50 μg/mL) and after restored with GSH (10 μM). B. Hg2+ concentration dependent PL quenching (red line) of CdTe QDs in ratiometric probe (50 µg/mL) and subsequent PL restoration (black line) by GSH (3 μM). All solutions were prepared in a 0.01 M PBS of pH 8.0.
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Figure 4. Selectivity of the Hg2+ quencher ratiometric probe to some coexisting species in the PB (pH 8.0, 0.01 M), including Na+ (1000 µM), K+ (1000 µM), Mg2+ (1000 µM), Ca2+ (1000 µM), L-Cysteine (Cys, 45 µM), proline (Pro, 100 µM), Phenylalanine (Phe, 100 µM), DL-Methionine (Met, 100 µM), natural -carotene (β-C, 100 µM), Tyrosine (Tyr, 100 µM), DL-malic acid (MA, 100 µM), vitamin E acetate (VE, 100 µM), citric acid (CA, 100 µM), glucose (Glu, 100 µM) and ascorbic acid (AA, 100 µM ). The fluorescence photos were selectivity of the Hg2+ quencher ratiometric probe to some coexisting species in the PBS (pH 8.0, 0.01 M).
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Figure 5. (A) Recovery of PL spectra at different concentrations of GSH after the Hg2+ (1.2 μM) quenching CdSe@SiO2@CdTe NPs (50 µg/mL). The concentrations of GSH from bottom to top are 0, 0.1, 0.5, 1, 2, 3, 5, 7, 10, 15, 20 and 30 µM, respectively. The fluorescence photos were taken under a UV lamp under the excitation of 365 nm. (B) Plot of the PL intensity ratio (I619/535) of the Hg2+ (1.2 μM) quenching nanohybrid as a function of the GSH concentration.
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Table 1. Comparison of the analytical performance of the sensing systems for the detection of GSH reference
probes
methods
modes
linear range
detection
(μM)
limit (nM)
ref.52
AA-Au NPs
colorimetry
turn-on
0.25-2.5
100
ref.53
Ag+–TMB
colorimetry
turn-off
0.05-8
50
ref.54
Au NPs–Hg(II)
colorimetry
turn-off
0.025–2.28
17
ref.55
MoS2/rGO
single emission
turn-off
60-700
25000
ref.56
Ag nanoclusters
single emission
turn-off
0.5–6
380
ref.57
Carbon dots–MnO2
single emission
turn-off
0–2500
300
ref.58
CDs-Br
single emission
turn-off
0–34
140
ref.59
CdTe−Hg(II)
single emission
turn-off
0.6-20
100
ref.60
Mn-doped ZnS QDs
single emission
turn-on
0.3-280
97
ref.61
C QDs
single emission
0-0.1
43
ref.62
DPP-NO2
single emission
turn-on
30-90
61.4
ref.63
Carbon dots-gold NPs
dual-mode
turn-on
0.1-6
50
2+
N- CQDs-RhB-Hg
dual-emission
turn-on
0.08–60
20
CdSe@SiO2@CdTe
dual-emission
turn-on
0-10
42
ref.64 this study
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Table 2. Applications of the proposed method for analysis of various food samples spiked with different amounts of GSH samples dark-shinned grape
pineapple
cucumber
tomato
initial amount
standard added
(mg/100 g)
GSH (µM)
1.79
1.13
1.17
6.24
recovery (%)
av recovery (%)
RSD (%)
2.0
102.3-105.5
104.0
1.10
4.0
99.2-103.5
101.5
1.47
6.0
98.3-102.5
99.1
1.42
2.0
99.5-103.1
100.7
1.59
4.0
97.4-103.6
101.3
2.53
6.0
96.6-99.2
97.6
1.13
2.0
97.8-104.1
101.5
2.43
4.0
96.4-100.9
98.7
1.58
6.0
95.6-101.2
98.1
2.11
2.0
96.2-102.6
98.7
3.42
4.0
97.6-103.1
101.1
2.30
6.0
98.9-99.5
99.1
0.27
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Visual Assay of Glutathione in Vegetables and Fruits Using
2
Quantum Dot Ratiometric Hybrid Probes
3
Aimin Chen,†,‡,* Xiao Peng, † Zaifa Pan, † Kang Shao, † Jing Wang, †,*
4
and Maohong Fan‡,§,*
5
6
†.
7
310014, China.
8
‡.
9
Laramie, WY 82071, USA.
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou
Departments of Chemical and Petroleum Engineering, University of Wyoming,
10
§.
11
Corresponding author: Aimin Chen, Email:
[email protected] School of Energy Resources, University of Wyoming, Laramie, WY 82071, USA.
12
Jing Wang, Email:
[email protected] 13
Maohong Fan, Email:
[email protected] 14
15
16
17
18
19
20
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ABSTRACT: Future food safety monitoring with simple, fast and visual methods has
22
become increasingly important. Accordingly, this work was designed to construct a
23
new-style dual-emission ratiometric fluorescent probe (CdSe@SiO2@CdTe) for
24
visual assay of glutathione (GSH) with a “turn on” strategy. After adding Hg2+, the
25
red fluorescence of the outer CdTe QDs was quenched through both electron transfer
26
and ion-binding processes. Upon the addition of glutathione, the red fluorescence
27
occurred again owing to the strong affinity between GSH and Hg2+, whereas the inner
28
green fluorescence of CdSe QDs kept unchanged, leading to a clearly recognizable
29
fluorescence color change (from green to orange-red). In the concentration range from
30
0.1 to 10 µM, the relative fluorescence intensity ratios (I619/I535) showed an excellent
31
linear correlation with the concentration of GSH, and the detection limit was as low as
32
42 nM under optimal conditions. Meanwhile, the quantum dot ratiometric hybrid
33
probes were successfully applied for direct visual sensing GSH in real vegetable and
34
fruit samples.
35
KEYWORDS: Quantum dots, ratiometric probes, mercury ions, glutathione, visual
36
detection, silica nanoparticle
37 38 39 40 41 42 43 44 45 46 47 48
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INTRODUCTION
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Glutathione (GSH), a small molecule peptide composed of three amino acids, is the
51
major free thiol present in virtually all animal cells. It plays a significant role in
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antioxidant defense and immune maintenance during life activities including
53
participation in bioreduction reaction of organisms, maintenance of enzyme activity,
54
preventing detoxification and oxidation/nitrification stress.1-4 Although human body
55
can produce GSH, it is far from meeting the needs of all kinds of activities of the body.
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The absence of GSH can lead to pressure, aging and a series of diseases, such as
57
Alzheimer, Parkinson, Diabetes, HIV, cancer, ect.5, 6 Therefore, the intake of foods
58
containing GSH is of great help to human health. Development of convenient
59
technology for monitoring GSH of foods is of great significance for food safety and
60
disease diagnosis. 7, 8
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Over the last few decades, various analytical methods have been applied to the
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mensuration of GSH, including mass spectrometry,9 high-performance liquid
63
chromatography,10 electrochemistry,11 colorimetry,12 and fluorescence.13 Among of
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them, fluorescence techniques have been
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specificity, high sensitivity,14 and the wide range of material sources including
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quantum dots and organic dyes, 15, 16 metal clusters,17 carbon dots (CDs),18 and so on.
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For instance, Wang et al designed a fluorescent probe based on gold nanoparticles to
68
detect GSH with high selectivity and ultra-sensitivity.19 Li et al. prepared Mn-doped
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CdTe quantum dots-methyl viologen nanohybrid to detect GSH,which has the
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advantages of a short detection time and the selective detection of GSH compared
widely explored due to their simplicity,
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with other biothiols.20 However, the main features of these fluorescent nanoprobes
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were the single-signal mode (turn-off or turn-on),and often affected by concentration
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of the probe, incident light, and external environment. Recently, ratiometric
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fluorescence analysis method has attracted great interest because of its dependability
75
and anti-interference ability by simultaneous measurement of two fluorescence signals
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under single wavelength excitation.21-23 For instance, An’s group reported a probe
77
combined by Rhodamine 6G and MPA-CdTe for highly sensitive detection of GSH
78
via the fluorescence resonance energy transfer mechanism with a LOD of 15 nM.24
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Qin et al. prepared two ratiometric fluorescent probes including nitrophenol groups
80
which exhibited outstanding excellent selectivity for GSH and have been successfully
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applied to the determination of GSH in cells.25 Despite these breakthroughs, there are
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still many deficiencies in the construction of dual signal transmitter for GSH,
83
especially in designing mensurable spectral responses in the emitting intensity and/or
84
wavelength. Therefore, it is still a challenging project to detect GSH accurately with
85
dual-emission fluorescent nanoprobe.
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Herein, we constructed a new-style dual-emission ratiometric fluorescent probe
87
(termed as CdSe@SiO2@CdTe) for visual detection of glutathione combined with
88
“turn on” strategy. As described in Scheme 1, the green fluorescence CdSe QDs were
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coated in silica spheres for covalent coupling of red fluorescence CdTe QDs modified
90
by N-acetyl-L-cysteine (NALC), in oreder to achieve both adjustable fluorescence
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intensity ratios and color. This ratiometric fluorescent probe has the following
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advantages. Firstly,
the dual-stabilizer modified CdSe QD was used as a reference
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instead of frequently-used CdTe QDs because
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atoms to MPA and SHMP could lead to QDs with excellent PL properties after silica
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coating.26,
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fluorescence not only can be effectively quenched by Hg2+ through both electron
97
transfer and ion-binding process but also be recovered readily in presence of the GSH.
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Meanwhile, compared with commonly used MPA stabilizer, NALC is more
99
environmentally friendly and stable which has a remarkable advantage for practical
100
applications.28, 29, 30 Based on the above superiority, the ratiometric fluorescent probe
101
has been well applied to detect GSH in vegetable and fruit samples with high
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sensitivity and selectivity.
27
Also, the signal reporter is CdTe QDs modified by NALC, whose
103
104
the bonding of surface cadmium
MATERIALS AND METHODS
105
Chemicals and Reagents. Cadmium chloride (CdCl2·2.5H2O, 99.95%), sodium
106
hexametaphosphate ((NaPO3)6, SHMP, 99%), sodium selenite (Na2SeO3, 99%),
107
sodium tellurite (Na2TeO3, 99.9%), 3-mercaptopropionic acid (MPA, 99%), tetraethyl
108
orthosilicate (TEOS, 99%), L-glutathione reduced (GSH, 98%), N-acetyl-L-cysteine
109
(NALC, 99%), DL-malic acid (99%), L-Cysteine (99%), Z-D-Tyrosine (98%),
110
phenylalanine, DL-methionine (99%), L-Proline (99%), natural β-carotene (96%),
111
3-aminopropyltriethoxysilane (APTES, 99%), vitamin E acetate (96%) and
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L-histidine (99%) were ordered from Aladdin Regent Co., Ltd. Sodium borohydride
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(NaBH4, 98%) was obtained from the Shanghai Ling Feng Chemical Reagent Co., Ltd.
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Hydrazine hydrate (N2H4·H2O, 85%), ammonium hydroxide (NH3·H2O, 25%), and
115
other frequently-used salts were acquired from Sinopharm Chemical Reagent Co., Ltd.
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Phosphate buffered saline (PBS) were obtained by combining PB solutions with 9%
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NaCl. Ascorbic acid (AA, 99.7%) was obtained from the Guangdong Guanghua
118
Polytron Technologies Inc. All the related chemical reagents were of analytical grade
119
and deionized water from a Millipore water purification system (≥18 MΩ.cm, Milli-Q,
120
Millipore) was used for preparing the solution.
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Instrumentation. Transmission electron microscopy (TEM) images were
122
investigated on FEI-F20 electron microscopy (FEI Corporation, USA) instrument
123
operating at 200 kV. Fourier-transform infrared (FTIR) data were recorded with a
124
Bruker model VECTOR22 Fourier-transform spectrometer using KBr pressed disks
125
(Bruker Corporation, Germany). X-ray photoelectron spectroscopy (XPS) was carried
126
out using a photoelectron spectrometer called AXIS Ultra DLD (Kratos Corporation,
127
Japan). Absorption spectra were gauged by SHIMADZU UV-2550 UV-Vis
128
spectrometer. Fluorescence decay curves were obtained by the time related single
129
photo counting technique on the combined steady-state and lifetime spectrometer
130
(Edinburgh Analytical Instruments, FLSP920). Photoluminescence (PL) spectra were
131
collected with a Horiba JY FluoroLog-3 spectrometer with an integrating sphere
132
attachment.
133
Synthesis of green-emitting dual-stabilizers-modified CdSe QDs. The synthesis
134
of CdSe QDs was based on a reported method.31 For a typical synthesis, 0.80 mL
135
CdCl2 solution (0.20 M) was diluted using 50 mL H2O in a flask; then in the magnetic
136
stirring, 34.60 µL MPA and then 72.50 mg SHMP were added into the solution. The
137
pH of the solution was regulated to 9.0 by using 1.0 M NaOH solution, followed by
138
injection of 0.80 mL Na2SeO3 solution (0.02 M). Subsequently, the obtained solution
139
was refluxed at 100 °C for 5 min and added 3.67 mL N2H4·H2O into the mixture. The
140
green CdSe QDs solution was obtained by refluxing for about 9 h. After
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centrifugation and washing with ethanol for several times, the depurated products
142
were obtained. Finally, the depurated CdSe QDs were dispersed and kept in deionized
143
water at 4 °C for next use.
144
Synthesis of amino group functionalized CdSe@SiO2 composite. Amino capped
145
CdSe@SiO2 fluorescent nanospheres were prepared by using a modified stöber
146
method.32 Specifically, 10 mL water was added toCdSe QDs (from 10 mL stocked
147
CdSe solution) for increasing dispersion,
148
and stirring it for 10 min. Then, 0.5 mL NH3·H2O (25-28 wt%) and 0.5 mL TEOS
149
was injected into the above solution and kept stirring for 12 h. Finally, 100 µL APTES
150
was introduced into in the mixed system and stirring for 12 h again. After
151
centrifugation, the precipitate was collected and cleaned using ethanol and deionized
152
water in sequence until the fluorescence of supernatant liquid disappeared. The
153
obtained amino capped CdSe@SiO2 fluorescent nanospheres were dispersed in
154
deionized water for experimental use.
followed by mixing it with 40 mL ethanol
155
Synthesis of red-emitting NALC-stabilized CdTe QDs. NALC-stabilized CdTe
156
QDs were prepared according to previous reports and improvements.33 Under the
157
protection of nitrogen flow, 0.0784 g NALC was added to 50 mL CdCl2 solution
158
(9.14×10-4 g/mL) and the pH of the solution was regulated to 11.0 by using 1.0 M
159
NaOH solution. Then 0.1075 g trisodium citrate dihydrate, 8.85 mg Na2TeO3 and 0.04
160
g NaBH4 were added into the above mixture in sequence. After refluxing at 100 °C for
161
14 h, the red CdTe QDs was obtained, followed by purification with by centrifugation
162
after adding the same volume of ethanol. The depurated CdTe QDs were dispersed
163
and maintained in deionized water at 4 °C for next use.
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Synthesis
of
CdSe@SiO2@CdTe
ratiometric
probe.
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The
red-emitting
165
NALC-stabilized CdTe QDs could covalently connect to the silica surface on the
166
basis of the reported literature.34 Briefly, 15 mg EDC was added to the 2 mL of CdTe
167
solution under magnetic stirring for 20 min. After adding 12 mg CdSe@SiO2–NH2 to
168
the above solution, the mixture was kept stirring in the dark for 12 h at room
169
temperature. By further centrifuging and washing with deionized water, the
170
dual-emission
171
CdTe@SiO2@CdSe ratiometric probes were dispersed and kept in deionized water at
172
4 °C for next use.
silica
nanocomposites
were
obtained.
The
depurated
173
Detection of GSH in buffer solution. The procedure for detecting GSH was as
174
follows. In a 3 mL calibrated test tube, 1 mL of PBS (pH 8.0, 10 mM), 0.15 mL of
175
ratiometric fluorescence probe (1.0 mg/mL) and 36 µL of Hg2+ (0.1 mM) were
176
injected in sequene. Then, different amounts of GSH (0–30 µM) were added to the
177
test tubes in turn and diluted to 3 mL by deonized water. After mixed solution was
178
kept at room temperature for 15 min, it was tested using the PL spectrum at the
179
excitation of 380 nm.
180
Detection of GSH in vegetables and fruits. The samples of vegetables and fruits
181
were prepared according to a previous report with a few modifications.35 First, all the
182
samples were cleaned with ultrapure water. Then the samples were weighed after they
183
were dried in the air, followed by rupture and gnash in a high speed blender. The
184
resulting supernatant was filtered using a 0.22 µm microporous filters and diluted to
185
the detection range with PBS (pH 8.0, 10 mM). One hundred micro filtration samples
186
with different concentrations were put in the texting solution, and their PL spectra
187
were detected under the same condition.
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RESULTS AND DISCUSSION
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Characterization of CdSe@SiO2@CdTe ratiometric hybrid probes. The optical
190
properties and structure of ratiometric hybrid probes were studied detailedly. The PL
191
spectra of CdSe@SiO2–NH2 NPs, NALC-CdTe QDs, and the ratiometric hybrid
192
probes are presented in Figure 1A. As curve a shown, the CdSe@SiO2–NH2 NPs
193
indicates an obvious emission peak centered at 533 nm as well as strong green
194
fluorescence under UV light (a of inset). For CdTe QDs, a PL ultimate peak appeared
195
at 609 nm (see curve b) with bright red fluorescence under UV light (b of inset). By
196
mixing the CdSe@SiO2–NH2 NPs with the CdTe QDs in a certain proportion,
197
ratiometric fluorescence probes were obtained with two PL peaks of 535 nm and 609
198
nm, respectively, showing orange red under UV light (c of inset). TEM images were
199
also investigated to verify the proper connection between the CdTe QDs and the
200
silicon dioxide spherical particles. As illustrated in Figure 1B, the as-prepared CdSe
201
QDs@SiO2 had uniform spherical structure with a diameter of 48.4±4.3 nm. The silica
202
coating could impede the immediate contact of the internal QDs with the outer
203
solvents during the connection and the subsequent test, generating a steady and
204
credible reference signal.36 As showed in Figure 1C, the prepared NALC-CdTe QDs
205
were nearly monodisperse with homogeneous size of 4.1±0.5 nm. A great deal of dark
206
“QD islands” were dispersed evenly on the surface of each silica sphere (shown in
207
Figure 1D), suggesting that the CdTe QDs had been successfully connected to the
208
silica shells due to the covalent link. Moreover, the FT-IR spectrum was taken to
209
obtain further structural insights about CdSe@SiO2@CdTe ratiometric hybrid probes.
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In Figure S1B, the peaks of CdSe@SiO2–NH2 NPs at 1045.1 cm−1 and 788.6 cm−1
211
were attributed to Si–O–Si stretch vibration. The new peak 1392.3 cm−1 appeared
212
after CdTe QDs was covalently connected to CdSe@SiO2–NH2 NPs. Compared with
213
Figure S1A, we can get that the peak represented the C–C stretching vibrations from
214
NALC.37 From CdSe@SiO2 to CdSe@SiO2@CdTe, the absorption peak of –NH2
215
shifted from 1637.7 cm-1 blue to 1628.8 cm-1, which might be the result of hydrogen
216
bonding between –NH2 on the surface of silicon dioxide and –COOH on the surface
217
of CdTe QDs.38-40 For further demonstrating
218
the surface of CdSe@SiO2, XPS characterization was conducted to detect surface of
219
CdSe@SiO2 before and after conjugation. In Figure S2, compared with the original
220
CdSe@SiO2, the emergence of new N1s, Te3d and Cd (3d, 4d) peaks in the
221
CdSe@SiO2@CdTe were attributed to NALC and CdTe respectively. The above
222
analysis indicated that the ratiometric hybrid probes were successfully obtained.41
the conjugation of outer layer QDs on
223
224
Sensing mechanism of CdSe@SiO2@CdTe ratiometric hybrid probe. Some
225
previous researches had reported that quenching quantum dots with Hg2+ with two
226
different mechanisms for quenching effect: Yan’s group showed that the quenching of
227
CdS QDs by Hg2+ was due to the formation of size-quantized HgS on the surface of
228
the particle, that is, the formation of ionic bonds leads to fluorescence quenching.42
229
Xia and co-workers reported the quenching mechanism of Hg2+ was complex:
230
Ion-binding and electron transfer co-existed, but electron transfer played a dominant
231
role.43 In our experiment, NALC played a crucial role, which was directly connected
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to the surface of CdTe QDs by sulfydryl. NALC contained sulfydryl and imino groups
233
which could be combined with Hg2+. The steric hindrance effect of NALC might
234
hinder the bonding between Hg2+ and sulfydryl.44 So, we assumed that these two
235
mechanisms also appeared in the quenching process. After Hg2+ was added, as
236
exhibited in Figure S3, the PL intensity of outer CdTe QDs decreased accordingly. In
237
addition, it was found that the addition of Hg2+ caused the red shift of the fluorescence
238
peak (up to 13 nm), which indicated that Hg2+ combined sulfydryl to generate HgS.45
239
Furthermore, this hypothesis was also verified by UV–Vis characterization. As
240
demonstrated in Figure S4, the maximum absorption peak had a red shift after
241
addition of Hg2+. When mixing GSH to the above system, it was found that a blue
242
shift of fluorescence peak occurred. In Figure 4A, the fluorescence intensity could
243
restore to the original 92% as GSH concentration reached 30 µM. The blue shift had
244
only 3 nm, which also confirmed that the electron transfer was the main cause of the
245
quenching process. Compared with the combination of imino group and Hg2+, the
246
combination of sulfydryl and Hg2+ was much stronger. According to the competitive
247
relationship of combination, after GSH was added, Hg2+ combined with imino group
248
in NALC would be replaced with the GSH. However, Hg2+ combined with sulfydryl
249
in NALC almost could not be released. Chen’s study also well verified our conjecture
250
that electron transfer played a dominant role in the quenching reaction.46
251
In order to analyze the quenching recovery performance of outer CdTe QDs, the
252
test of fluorescence lifetime was investigated. Because the fluorescence intensity of
253
the probe did not change at the 535 nm (Figure 4A), we studied the fluorescence
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lifetime by monitoring 609 nm. The decays of all the samples were multiexponential.
255
After fitted using the third-order equation, the data are presented in Table S1. Figure 2
256
presents the fluorescence decay curves, including original probe (black line),
257
quenched by Hg2+ (red line) and recovered by GSH (blue line). After adding Hg2+ into
258
the original probe system, the lifetime of outer CdTe QDs was substantially decreased
259
from 22.76 to 13.95 ns. The decreasing of lifetime was owing to the electron transfer
260
from QDs to Hg2+.47 In order to restore the lifetime of CdTe QDs, addition of GSH is
261
a key element to motivet the separation of Hg2+ from probe through a strong
262
interaction between Hg2+ and GSH, which resulted the restore of the lifetime from
263
13.95 to 23.84 ns.
264 265
Optimizations of experimental conditions
266
Choice of pH. The appropriate pH buffering system is vital to achieving a
267
favorable analytical property for the fluorescent detection of GSH. So, we studied the
268
quenching and recovery process in PBS buffer (10 mM) respectively in order to find
269
the most suitable pH. In Figure 3A, the pH range changed from 5.5 to 9. Each sample
270
was added with the same concentration of Hg2+ (1.2 µM), the fluorescence intensity
271
increased slightly with the increase of pH and tended to be steady at the vicinity of pH
272
8.5; after adding 10 µM GSH, the fluorescence intensity increased greatly and tended
273
to be stable at pH 8.0. It was found that the interaction between GSH and Hg2+ in
274
alkaline medium was stronger than that in acidic solution, which was consistent with
275
previous report.48 According to the above results, the optimal pH was 8.0 for detection
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condition. Choice of Hg2+ concentration.
The effect of Hg2+ on the test sensitivity of the
278
probe under pH 8.0 was evaluated. As displayed in Figure 3B, the PL intensity of
279
outer CdTe QDs significantly decreased with the increasing concentration of Hg2+
280
(0.2−1.5 µM). In addition, when the amount of GSH was the same, the PL intensity
281
ratio (∆(I619/I535)) of the probe (red line) enhanced gradually and reached the
282
maximum value at 1.2 µM. With the further increase in Hg2+, the
283
drop. Based on the above results, 1.2 µM of Hg2+ was chosen as the optimal
284
quenching concentration for ratiometric detection.
change started to
285
286
Other influencing factors. In order to achieve a superior performance of
287
ratiometric probe, a series of tests were carried out, including photostability,
288
long-term stability, reaction time, and concentration of GSH. As shown in Figure S5A,
289
the stability of the probe was examined under UV light. After ten continuous lighting
290
with 5 min for each time, it was found that the relative fluorescence intensity ratios
291
(I609/I535) of the probe had not changed essentially. Furthermore, indicated in Figure.
292
S5B, after 90 days' static position, there were no obvious changes concerning the
293
fluorescence intensity ratio (I609/I535) of the probe, indicating the high long-term
294
stability. The gauging of reaction time is depicted in Figure S6A. With the increasing
295
of Hg2+ concentration, the fluorescence intensity of the CdTe QDs decreased rapidly.
296
After about 5 minutes, the fluorescence intensity tended to be stable. In addition, the
297
binding of GSH to Hg2+ was accompanied by the separation of NALC and Hg2+.
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Therefore, the reaction time was longer, and the fluorescence recovery was almost
299
unchanged after 10 minutes (Figure S6B). We also investigated the effect of
300
concentration of GSH (0−60 µM) over the probe and the results are presented in
301
Figure S7. The fluorescence intensity of probe had no change basically as the
302
concentration of GSH increased, which eliminated GSH effect on the probe itself.
303
Selectivity of the ratiometric hybrid probe. For the sake of estimating the
304
selectivity of this probe to detect GSH, it is necessary to detect some biological
305
molecules in real samples which might coexist with GSH. As shown in Figure 4, Na+,
306
K+, Mg2+, Ca2+, proline, phenylalanine, Tyrosine and vitamin E acetate had little effect
307
on the reaction system. Citric acid, glucose and ascorbic acid caused fluorescence
308
quench lightly in accompaniment with the deep green color. DL-Methionine and
309
natural β-carotene led to fluorescence recover slightly. However, cysteine is an
310
exception, which could restore fluorescence to a certain extent. It was speculated that
311
the binding force between GSH and Hg2+ was far greater than cysteine binding to the
312
Hg2+ .49, 50 The design of interaction between GSH and Hg2+ enabled to recognize
313
GSH from other small sulfydryl species, which was different from reported
314
techniques.51 The desirable results indicated higher selectivity of this probe which
315
would have a potential application prospect.
316
317
Detection of GSH by CdSe@SiO2@CdTe ratiometric probe. Then, we
318
conducted some more experiments to study the change of fluorescence intensity of
319
probe with the increase of the amount of GSH (Figure 5A). With the concentration of
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GSH increasing from 0 to 30 µM, the PL peak at 619 nm increased, however it barely
321
changed at 535 nm. In Figure 5B, fluorescence intensity ratio (I619/I535) expressed a
322
perfect linear relationship in the GSH concentration range (0-10 µM), the linear
323
regression equation of calibration curve was expressed as I619/I535 =0.4262+0.0833c,
324
in which c represents the concentration of GSH, the detection limit for GSH was
325
calculated as 42 nM (S/N=3). Compared with other researches in the reported
326
literatures for GSH detection, this fluorescent method shows either comparable or
327
even better response (Table 1). Moreover, under a UV light (365 nm), the variety of
328
fluorescence intensity ratio also led to obvious change of the fluorescence color from
329
green to orange-red (inset of Figure 5A). The obvious color change made it as a visual
330
assay of GSH advantageous. In order to prove the superiority of the ratiometric
331
fluorescence for visual assay, we did the single fluorescence experiment. As shown in
332
Figure S8, a single red NALC-CdTe QD probe was applied for the detection of GSH
333
compared with ratiometric probe. However, it was difficult to find out the
334
fluorescence color change of the single CdTe probe (inset of Figure S8). The above
335
results distinctly confirmed that the ratiometric fluorescence probe provided higher
336
creditability and sensitivity as a visual assay than a single fluorescence probe did.
337
338
Detection of GSH in vegetables and fruits. The feasibility was explored for
339
detecting glutathione in real samples such as fruits and vegetables by using the
340
ratiometric fluorescent probe. Before testing samples, the effect of sample matrix on
341
the detection system was analyzed. After adding a certain amount of food samples, the
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fluorescence of the system had not changed basically (Figure S9). So it could also
343
eliminate the influence of matrix on the whole testing system. In addition, we added
344
different amounts of GSH (2.0, 4.0 and 6.0 µM) to conduct the recovery experiment
345
and detailed results were displayed in Table 2. The percent recoveries of GSH in
346
diluted samples were between 96.2% and 105.5%, satisfying with the quantitative
347
analysis in the actual samples. The relevant fluorescence pictures were taken under
348
the same UV light condition (365 nm) (Figure S10). These results proved that the
349
designed fluorescence technique could be further developed as a platform for visual
350
assay of GSH in actual samples. The present method was applied to analyze different
351
amounts of GSH in various food samples.
352
In conclusion, in view of the ratiometric QDs nanohybrid, we have designed a
353
simple, ingenious and highly selective fluorescence signal analysis method to detect
354
GSH. The fluorescence of outer CdTe QDs was quenched by inducing Hg2+ due to the
355
existence of electron transfer and ion-binding. After the addition of GSH, the outer
356
fluorescence recovered while the internal CdSe QDs fluorescence remained
357
unchanged, which leaded to fluorescence color change from green to orange-red.
358
Selective experiments showed that even with sulfur-containing amino acids, the
359
detection of glutathione could not be interfered, and this technique was successfully
360
applied to visual assay of GSH in real fruits and vegetables. We expect that this work
361
will spread out the way for the development of new visual technique for future food
362
safety analysis.
363
AUTHOR INFORMATION
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Corresponding Authors
365
* Phone/Fax: 0086-571-88320284; E-mail:
[email protected] 366
* Phone/Fax: 0086-571-88320238;
[email protected] 367
* Phone/Fax: 001-307- 7665633; E-mail:
[email protected] 368
ORCID
369
Aimin Chen: 0000-0002-9189-3726
370
Jing Wang: 0000-0003-3185-1724
371
Maohong Fan: 0000-0003-1334-7292
372
Funding
373
This work was supported by the Key projects of Zhejiang Natural Science Foundation
374
(LZ18B050002) and Public Project of Zhejiang Province (2017C33172).
375
Notes
376
The authors declare no competing financial interest.
377
Reference
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