A novel quinoline-based colorimetric fluorescent probe for hydrogen sulfide

Article abstract of DOI:10.1177/1747519820924589

In this article, a novel fluorescent probe was designed and synthesized based on the quinoline structure for the detection of H₂S. After optical evaluation, the probe showed good characteristics, including a fast response, high sensitivity, and good selectivity. More importantly, the probe could be directly observed by the naked eye after responding to H₂S and has good application value.

Full text of DOI:10.1177/1747519820924589

9
research-arti
2cle2020 4589CHL0010.1177/1747519820924589Journal of Chemical ResearchFu
Research Paper
Journal of Chemical Research
–4
1
A novel quinoline-based colorimetric
fluorescent probe for hydrogen sulfide
© The Author(s) 2020
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Dingqiang Fu
Abstract
In this article, a novel fluorescent probe was designed and synthesized based on the quinoline structure for the detection
of H S. After optical evaluation, the probe showed good characteristics, including a fast response, high sensitivity, and
2
good selectivity. More importantly, the probe could be directly observed by the naked eye after responding to H S and
2
has good application value.
Keywords
fluorescent probe, hydrogen sulfide, quinoline structure
Date received: 15 February 2020; accepted: 14 April 2020
Introduction
Herein, based on a review of the literature, we report the
design of hydrogen sulfide fluorescent probe 6 that has a
quinoline group connected to a dinitrophenyl ether through
a styrene linker. After reacting with hydrogen sulfide, the
dinitrophenyl ether group was removed, releasing a hemi-
cyanine chromophore. The probe is simple and easy to
obtain, and the raw materials required for the synthesis are
readily available (see Scheme 1). Probe 6 in a phosphate-
buffered saline (PBS/dimethyl sulfoxide (DMSO)=6:4,
v/v, pH=7.4) solution achieved rapid and selective colori-
metric recognition of hydrogen sulfide.
Hydrogen sulfide (H S), a colorless gas with the smell of
rotten eggs, has long been considered a highly toxic gas and
environmental pollutant. However, in recent years, numer-
ous studies have shown that hydrogen sulfide has important
physiological functions and is an important biological and
2
1
2
pharmacological medium at nanomolar to millimolar lev-
els. In mammals, endogenous hydrogen sulfide is mainly
derived from the metabolism of l-cysteine and homocyst-
3
eine. Numerous studies have also shown that hydrogen
4
sulfide has a dual effect on the growth of tumor cells. In
addition, hydrogen sulfide has potential therapeutic value
for several central nervous system diseases such as Results and discussion
5
6
Alzheimer’s disease (AD), Parkinson’s disease (PD),
The synthesis of probe 5 is detailed in the three steps
shown in Scheme 1. First, (E)-4-(2-(quinolin-2-yl)vinyl)
phenyl acetate 3 was synthesized from 2-methylquinoline
and 4-hydroxybenzaldehyde and second, compound 3 was
hydrolyzed under basic conditions to obtain intermediate
7
ischemic stroke, and traumatic brain injury (TBI).
Considering the potential of hydrogen sulfide–based
treatments, the detection of H S is crucial, so various meth-
2
8
ods have been developed for detection, such as colorimetry,
titration, chromatography, electrochemical, and fluores-
cent probe detection methods. Among these, fluorescent
probes have attracted much attention due to their high sensi-
tivity, fast response, and convenient operation. In recent
9
10
11
4
. Finally, intermediate 4, 2,4-dinitrobenzene, and methyl
12
years, significant research into hydrogen sulfide fluorescent Sichuan University, Collaborative Innovation Center of Sichuan
1
3–17
probes has been carried out rapidly.
fluorescent scaffolds that have been used include cou-
The main types of University, Chengdu, P.R. China
Corresponding author:
18–20
21,22
23–25
marins,
nary pyridine salts,
isophoronitriles,
fluoropyrroles,
benzopyrandicarbonitriles,
naphthalenes, quinolines, and the like.
quater-
Dingqiang Fu, Sichuan University, Collaborative Innovation Center of
Sichuan University, Chengdu 610041, P.R. China.
Email: fuscu2@163.com
2
6–28
29,30
31
32,33

2
Journal of Chemical Research 00(0)
OH
NaOAc
,
Ac
2
O
NaOH MeOH
,
+
N
N
N
OHC
120
ꢀC
OAc
OH
1
2
3
4
Cl
NO
2
4
+
1
.
K
2
CO
3
, DMF
N
O
2
N
NO
2
2
.
CH
3
I
,
MeCN
,
reflux
I
O
NO
2
5
6
Scheme 1. Synthesis of fluorescent probe 6.
Figure 1. Absorption spectral changes of probe 6 (10μM) in
the absence and presence of sodium sulfide (100μM) in buffer
solution (PBS:DMSO=6:4, v/v, pH=7.4) with λex at 350nm.
iodide were used to prepare probe 6 under reflux condi-
tions. Its structure was fully characterized by elemental
1
13
analysis, UV-Vis, H NMR, C NMR, and electrospray Figure 2. (a) Absorption spectra of 6 (10μM) on the addition
of increasing concentrations of sodium sulfide (0, 2, 4, 6, 8, 10,
ionization mass spectra (ESI-MS).
1
5, 20, 25, 30, 35, 40, 45, 50, 60, and 70µM). (b) Absorption
With the probe in hand, 5 equiv. of aqueous sodium
sulfide was added to 10µM of a solution of probe 6 (PBS/
DMSO=6:4, pH=7.4), and the reaction between the probe
and sodium sulfide was observed. The UV absorption spec-
intensity changes of probe 5 at 590nm as a function of sodium
sulfide concentration.
tra at 0, 2, 4, 6, 8, 10, 12, 14, 16, and 18min are shown in When the sodium sulfide concentration was in the range
Figure 1. With longer reaction times, the absorption peak of of 0–70 µM, the absorbance of probe 6 at 590 nm had a
the probe at 390nm disappeared and a new absorption band linear relationship with the sodium sulfide concentra-
appeared at 590nm. After 14min, the UV absorption lev- tion with a correlation coefficient of 0.977. Moreover,
eled off reaching a maximum after 18min (Figure 1). the fluorescence spectrum was measured following the
Therefore, the reaction between probe 6 and sodium sulfide addition of the sodium sulfide solution (0, 2, 4, 6, 8, 10,
was complete in 18min and hydrogen sulfide could be 20, 30, 40, 50, 60, and 70 µM). As shown in Figure 3,
detected quickly.
the fluorescence intensity of the probe at 500 nm gradu-
Next, the emission behavior of the probe with differ- ally decreased. When sodium sulfide was added at a
ent concentrations of sodium sulfide was investigated. concentration of 20 µM, the fluorescence intensity was
The solution of probe 6 (PBS/DMSO = 6:4, pH = 7.4) reduced to the minimum. In addition, the blue fluores-
was added to different concentrations of solution of cence of the solution was observed to disappear under a
sodium sulfide solution (0, 2, 4, 6, 8, 10, 15, 20, 25, 30, UV lamp (365 nm). When the concentration of sodium
3
5, 40, 45, 50, 60, and 70 µM), and the absorption spec- sulfide is in the range of 0–10 µM, the fluorescence
trum was measured after 20 min. The results are shown intensity of probe 6 at 500 nm has a good linear relation-
in Figure 2. With an increase in sodium sulfide concen- ship with the concentration of sodium sulfide, with a
tration, the absorption peak of the probe at 390 nm grad- correlation coefficient of 0.991.
ually decreased and a new absorption band appeared at
90 nm and then gradually increased reaching the maxi- most important due to the complexity of biological sam-
Of all the factors, the selectivity of the probe is the
5
mum when the sodium sulfide concentration was 70 μM. ples. Therefore, the effects of 11 common anions and
In addition, the color of the solution was observed to reduced thiol Cys on the fluorescence intensity of probe 6
−
−
change from pale yellow to blue with the naked eye. were investigated. After adding 5 equiv. of Na S, F , Cl ,
2

Fu
3
Figure 4. Fluorescence enhancements at 450nm of probe 6
(
1
8
10μM) on addition of 10 equiv. of interfering analytes.
: blank; 2: Na S; 3: NaF; 4: NaCl; 5: NaHSO ; 6: NaOAc; 7: NaH PO ;
2
3
2
4
: Na SO ; 9: NaHCO ; 10: Na CO ; 11: NaNO ; 12: NaI; 13: Cys.
2
4
3
2
3
2
Conclusion
In this article, the design and synthesis of the colorimetric
fluorescence–enhanced probe 6 for the selective detection
of hydrogen sulfide are reported. By adding sodium sulfide,
the color of the solution of probe 6 could be observed with
the naked eye to change from pale yellow to blue. With the
increase in sodium sulfide concentration, the maximum flu-
orescence emission intensity of probe 6 at 490nm gradually
decreased. A good linear relationship was found between
the sodium sulfide concentration (0–10µM) and the fluores-
Figure 3. (a) Fluorescence spectra of 6 (10μM) on the
addition of increasing concentrations of sodium sulfide (0, 2, 4,
2
cence intensity (R =0.991). More importantly, the probe
could be used as a colorimetric and highly selective fluores-
cent probe for the rapid detection of sulfur hydrogen.
6
(
, 8, 10, 20, 30, 40, 50, 60, and 70µM) when excited at 350nm.
b) Fluorescence intensity changes of probe 6 at 500nm as a
function of sodium sulfide concentration.
Experiments
−
−
2−
4
2−
3
I , H PO , AcO , SO , CO , HCO ,
, Cys, and All the reagents and solvents were purchased from commer-
2
−
4−
3−
NO2
−
HSO3 sodium salts to the solution of probe, the fluores- cial suppliers and used without further purification. The
cence spectra were measured. The results are shown in compounds used for the selectivity studies were Na S, NaF,
2
Figure 4. Only Na S significantly reduced the fluores- NaCl, NaI, NaH PO , NaOAc, Na SO , Na CO , NaHCO ,
2
2
4
2
4
2
3
3
cence intensity of probe 6. Therefore, probe 6 can selec- NaNO , Cys, and NaHSO . The water used in the experi-
2
3
tively detect hydrogen sulfide.
It is well known that H S can induce the departure of purification system. H nuclear magnetic resonance (NMR)
ments was ultrapure water purified by a Millipore water
1
2
13
2
,4-dinitrobenzene in aqueous solution, and this strategy and C NMR were measured on a Bruker AVANCE III400
has been successfully applied to construct various reac- MHz spectrometer with tetramethylsilane (TMS) as an
tion-based fluorescence sensors for the detection of internal standard, and chemical shifts were reported in ppm.
1
2,15,21
H S.
Probe 6 may be cleaved to release a quinoline UV absorption spectra were taken on a PERSEE TU-1900
2
on action with H S, resulting in detectable changes in the spectrophotometer. Fluorescence spectra were recorded
2
fluorescence spectrum. In addition, probe 6 itself had using a CARY Eclipse fluorescence spectrophotometer.
an intramolecular charge transfer (ICT) under the action
The intermediates 3 and 4 were synthesized according to
of an electron-withdrawing group (2,4-dinitrobenzene) the routes reported in the literature.34
and had the highest fluorescence intensity. When hydro-
Compound 4 (494mg, 2mmol), 2,4-dinitrochlorobenzene
gen sulfide reacts with the probe, 2,4-dinitrobenzene is (425mg, 2.2mmol), and anhydrous potassium carbonate
expelled, and the mechanism of ICT action disappears so (331mg, 2.4mmol) were sequentially added to 5mL of
that the fluorescence intensity was decreased. In addition, dimethylformamide (DMF) and allowed to react overnight at
1
we used a H NMR titration experiment to prove that H S room temperature. After the reaction was completed, 20mL of
2
can cause the departure of 2,4-dinitrobenzene and the water was added to the reaction mixture that was then extracted
appearance of a hydroxyl at 9.83ppm (Scheme 2).
with ethyl acetate (3×20mL). The organic phases were

4
Journal of Chemical Research 00(0)
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
ORCID iD
Dingqiang Fu
https://orcid.org/0000-0003-3472-7008
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6
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