A new fluorescent probe for ultrasensitive detection of phosgene in solution and the gas phase

Article abstract of DOI:10.1039/d1nj00037c

Due to the high toxicity and commercial availability of phosgene, it is urgent to detect phosgene quickly and reliably to deal with its potential serious threat to public safety. A new 2-(2-aminophenyl)quinazolin-4(3H)-one (APQ) based fluorescent probeAPQhas been developed as a rapid, highly sensitive, and selective sensor for phosgene in this work.APQdisplays very weak fluorescence in acetonitrile due to the free rotation of the 2-aminophenyl moiety. After reacting with phosgene,APQis converted to a new restricted intramolecular motion productAPQU1. Owing to the specific cyclization reactions,APQexhibits an obvious fluorescence response toward phosgene with a large Stokes shift (104 nm), instant response (less than 20 s), and low detection limit (0.16 ppm). Moreover, theAPQ-loaded test strip was prepared and demonstrated to have practical utility in detecting phosgene vapor.

Full text of DOI:10.1039/d1nj00037c

NJC
View Article Online
View Journal | View Issue
PAPER
A new fluorescent probe for ultrasensitive
detection of phosgene in solution and the gas
Cite this: New J. Chem., 2021,
4
5, 5631
phase†
Fenfen Zeng, Guangbo Bao, Baocheng Zhou and Yifeng Han
*
Due to the high toxicity and commercial availability of phosgene, it is urgent to detect phosgene quickly
and reliably to deal with its potential serious threat to public safety. A new 2-(2-aminophenyl)quinazolin-
4
(3H)-one (APQ) based fluorescent probe APQ has been developed as a rapid, highly sensitive, and
selective sensor for phosgene in this work. APQ displays very weak fluorescence in acetonitrile due to
the free rotation of the 2-aminophenyl moiety. After reacting with phosgene, APQ is converted to a new
restricted intramolecular motion product APQU1. Owing to the specific cyclization reactions, APQ
exhibits an obvious fluorescence response toward phosgene with a large Stokes shift (104 nm), instant
response (less than 20 s), and low detection limit (0.16 ppm). Moreover, the APQ-loaded test strip was
prepared and demonstrated to have practical utility in detecting phosgene vapor.
Received 4th January 2021,
Accepted 23rd February 2021
DOI: 10.1039/d1nj00037c
rsc.li/njc
advantages of good selectivity, high sensitivity, and simple
operation, and real-time and online detection. It has a wide
Phosgene (COCl ), used as a chemical weapon agent during range of applications in the fields of analysis, biology, the
1
. Introduction
1
4
2
1
–3
World War I, is a highly toxic, colorless gas.
The safe environment, etc. With these advantages, so far, researchers
4
exposure limit of phosgene is 0.1 ppm. Excessive inhalation have designed and developed more than twenty fluorescent
of phosgene can cause significant damage to the human lungs sensors that can be used for phosgene detection. These probes
and respiratory tract, resulting in suffocation, emphysema, are mainly: (1) based on the dual-active reaction characteristics
5
,6
pulmonary edema, and even death.
However, as a cost- of phosgene, where the two nucleophilic reaction sites of the
effective organic intermediate, phosgene has the advantage of recognition group (usually o-phenylenediamine or ethylenedia-
high reactivity and is widely used in the pharmaceutical, mine or ethanolamine, etc.) react with phosgene through the
7
,8
pesticide, and plastic industries. However, because phosgene reaction, which will regulate the photo-induced electron transfer
is widely used and readily available, it is more likely to cause (PET) or the internal charge transfer (ICT) effect in the probe,
1
5
phosgene to leak or be used as a chemical weapon by terrorists. and thus complete the recognition process; (2) based on the
It will pose a severe threat to public health and safety. Therefore, oxidation reaction characteristics of phosgene, with the usage
the development of a reliable, fast, and sensitive method for of the rearrangement reaction between phosgene and the oxime
detecting phosgene is essential.
or amide in the recognition group to identify the changes in
Subsequently, many analytical methods, including liquid the electron arrangement of the probe before and after the
9
,10
11
12
16
chromatography-mass spectrometry, colorimetry, luminescence,
response.
These phosgene fluorescent probes generally use 1,8-
1
3
and electrochemistry, have been developed to detect phos-
gene. These methods generally require sample pretreatment naphthalimide, coumarin, anthracenecarboxamide, BODIPY, rho-
and special expensive precision instruments or professional damine, etc., as fluorophores, and most of them can respond to
operators. Therefore, it is difficult to apply to the rapid on-site phosgene with high selectivity and sensitivity. However, it should
detection of phosgene in suspicious samples under the current be pointed out that many probes have a small Stokes shift, which
situation. The fluorescence probe detection method has the will cause fluorescence self-absorption and signal crosstalk,
thereby reducing the accuracy of detection. Besides, some probes
use fluorophores that are susceptible to rapid photobleaching,
leading to insufficient detection limits. Therefore, the design and
development of a phosgene fluorescent probe with high photo-
stability and large Stokes shift are of great significance to improve
the accuracy and sensitivity of phosgene detection.
Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou, 310018, China.
E-mail: zstuchem@gmail.com; Tel: +86-751-86843550
†
Electronic supplementary information (ESI) available: Experimental details,
characterization of the compounds, and additional spectroscopic data. See DOI:
0.1039/d1nj00037c
1
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2021
New J. Chem., 2021, 45, 5631–5636 | 5631

View Article Online
Paper
NJC
LS55 Fluorescence spectrophotometer. Absorption spectra were
collected on a Shimadzu UV 2501(PC)S UV-Visible spectrophoto-
meter. The excitation and emission widths for APQ were all 5/5.
2
.2. Synthesis of the probe
-(2-Nitrophenyl)quinazolin-4(3H)-one. 2-Aminobenzamide
2 g, 14.29 mmol) and 2-nitrobenzaldehyde (2.33 g, 15.42 mmol)
2
(
were dissolved in ethanol (15 mL) under a nitrogen atmo-
sphere, and then copper chloride (5.01 g, 29.38 mmol) was
added, and the reaction mixture was allowed to reflux for 16 h
until all starting material got consumed which was monitored
by TLC analysis. Then an aqueous sodium sulfide solution
(10 mL) was added and the black precipitate was removed
while hot. After cooling the filtrate, a yellow solid precipitate
appeared, and the solid was filtered and dried to obtain
compound 2-(2-nitrophenyl)quinazolin-4(3H)-one (2.2 g, 56%).
1
6
H NMR (400 MHz, DMSO-d ) d 12.85 (s, 1H), 8.25–8.17 (m, 2H),
7
.95–7.80 (m, 4H), 7.66 (d, J = 8.1 Hz, 1H), 7.61–7.55 (m, 1H).
1
3
C NMR (101 MHz, DMSO-d ) d 161.55, 151.71, 148.54, 147.47,
6
1
34.70, 133.96, 131.57, 131.54, 129.20, 127.39, 127.16, 125.93,
Scheme 1 Some reported phosgene fluorescent probes and the design
strategy of this work.
+
124.58, 121.20. HR-MS (TOF-ESI): calcd. for ([M + H]) ,
2
68.0717; found, 268.0722.
-(2-Aminophenyl)quinazolin-4(3H)-one (APQ). 2-(2-Nitrophenyl)
quinazolin-4(3H)-one (300 mg, 1.12 mmol) was dissolved in ethanol/
dioxane solution (1 : 1, v/v, 14 mL) under a H atmosphere, and then
0% Pd/C was added, and the reaction mixture was stirred for 24 h
2
2-(2-Hydroxyphenyl)quinazolin-4(3H)-one (HPQ) is a type of
fluorophore with an aggregation-induced fluorescence
2
1
7
enhancement (AIE) effect and possesses good photostability.
1
At the same time, the excited state intramolecular proton
transfer (ESIPT) effect in the molecule gives HPQ a larger Stokes
shift. Inspired by this, we intend to use the HPQ analog 2-(2-
aminophenyl)quinazolin-4(3H)-one (APQ) to detect phosgene
until all starting material got consumed which was monitored
by TLC analysis. The reaction mixture was quickly passed
through a short Celite column to remove Pd/C, and the solvent
was removed, then water (30 mL) was added, and extracted with
dichloromethane (3 ꢀ 15 mL). The extract was washed with
brine (45 mL), dried over sodium sulfate and then concentrated
under vacuum. The crude solid was collected and crystallized
(Scheme 1). We hypothesize that APQ may have AIE and ESIPT
effects similar to HPQ. Then, in a good solvent (such as the
commonly used phosgene test solvent acetonitrile or chloro-
form, etc.), APQ is in a dissolved state, and should exhibit no
fluorescence emission. However, when phosgene is present, the
amine and amide groups in APQ can react with the di-acid
chloride in phosgene to form urea, which restricts the rotation
from ethanol to get 2-(2-aminophenyl)quinazolin-4(3H)-one
1
(
157 mg, 59%) as a pale yellow solid. H NMR (400 MHz,
DMSO-d ) d 12.14 (s, 1H), 8.13 (d, J = 7.9 Hz, 1H), 7.81 (t, J =
6
7.7 Hz, 1H), 7.73 (t, J = 7.0 Hz, 2H), 7.48 (t, J = 7.5 Hz, 1H), 7.20
1
8
of molecules and generates fluorescence, thereby achieving
high selectivity detection of phosgene. Besides, the AIE effect in
APQ can guarantee its solid-state fluorescence emission so that
a test strip loaded with APQ might be used to detect
phosgene vapor.
(
t, J = 7.7 Hz, 1H), 7.08 (s, 2H), 6.83 (d, J = 8.2 Hz, 1H), 6.60 (t, J =
.5 Hz, 1H). C NMR (101 MHz, DMSO-d ) d 162.14, 153.69,
6
49.44, 147.98, 134.49, 131.81, 128.88, 126.78, 126.18,
13
7
1
1
25.74, 120.45, 116.62, 115.00, 112.39. HR-MS (TOF-ESI): calcd.
+
for ([M + H]) , 238.0975; found, 238.0983.
5
H-Quinazolino[4,3-b]quinazoline-6,8-dione (APQU1). 2-(2-
Aminophenyl)quinazolin-4(3H)-one (24 mg, 0.1 mmol) and
triphosgene (45 mg, 0.15 mmol) were dissolved in dioxane
2
. Experimental section
2.1 Reagents, materials, and apparatus
(3 mL), and then triethylamine (0.02 mL, 0.15 mmol) was
All the solvents used in the experiment were of analytical grade. added, and the reaction mixture was stirred for 30 min until
The reaction progress was monitored by thin-layer chromato- all starting material got consumed which was monitored by
graphy (TLC) on silica gel plates (GF254) visualized by UV light. TLC analysis. The solid in the reaction mixture was then filtered
2
00–300 mesh silica gel was used for column chromatography. and dried to obtain the product 5H-quinazolino[4,3-b]quinazo-
1
NMR experiments were carried out on a Bruker AV-400 NMR line-6,8-dione (20 mg, 75%) as a yellow solid. H NMR
spectrometer with chemical shifts reported in ppm (in CDCl3, (400 MHz, DMSO-d ) d 12.07 (s, 0.21H), 11.50 (s, 0.55H), 8.96
6
d6-DMSO, or TMS as an internal standard). Mass spectra were (d, J = 8.8 Hz, 0.3H), 8.39 (dd, J = 8.5, 5.5 Hz, 0.89H), 8.15 (dd,
measured on an Agilent 1290 LC-MS spectrometer. All pH J = 8.0, 1.5 Hz, 0.91H), 7.94–7.78 (m, 0.93H), 7.71 (t, J = 7.2 Hz,
measurements were made with a Sartorius basic pH-Meter 0.95H), 7.66–7.57 (m, 0.96H), 7.53 (t, J = 7.5 Hz, 0.64H), 7.32 (t,
PB-10. Fluorescence spectra were determined on a PerkinElmer J = 7.6 Hz, 0.34H), 7.28–7.21 (m, 0.89H), 7.15 (d, J = 8.1 Hz,
5632
|
New J. Chem., 2021, 45, 5631–5636
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2021

View Article Online
NJC
Paper
1
3
0
1
1
1
.67H). C NMR (101 MHz, DMSO-d
6
) d 166.43, 159.41, 147.40, of APQ in acetonitrile/water mixtures with different water
45.83, 145.55, 138.03, 137.55, 135.25, 135.19, 133.78, 132.77, content.
27.38, 127.37, 126.92, 126.83, 126.79, 126.65, 123.31, 122.98,
21.58, 121.41, 115.12, 114.91. HR-MS (TOF-ESI): calcd. for the good solvent acetonitrile, which may be due to the free
[M + H]) , 264.0768; found, 264.0771.
As we expected, APQ has almost no fluorescence emission in
+
(
rotation of 2-aminophenyl in the molecule (Scheme 1). When
the water content in the acetonitrile/water mixture increases,
the solubility of APQ in the system gradually decreases and
2
.3 Phosgene sensing in solution
Since phosgene is a highly toxic gas, it is replaced by triphos- induces the formation of nano-aggregates. As shown in Fig. 1,
gene, which is less volatile and toxic. Triphosgene can be although the fluorescence intensity of APQ remains low when
quickly decomposed by the action of tertiary amines (such as the water content is less than 80%, it increases rapidly as the water
TEA) to release phosgene. The APQ stock solution (1 mM) was content increases from 80% to 99%. The strong fluorescence
diluted by CH CN to 10 mM as a test solution. The detection of emission of APQ in this aggregated state may be due to the
3
1
8
phosgene and interfering substances was carried out by adding restricted intramolecular motion (RIM). In addition, APQ
solutions of thionyl chloride (SOCl ), phosphorus oxychloride exhibits a large Stokes shift (85 nm) in the water/acetonitrile
2
(
POCl
phosphate (DCP), acetyl chloride (CH
3
), p-toluenesulfonyl chloride (TosCl), diethyl chloro- system with 99% water content, indicating that the ESIPT
COCl), sulfonyl chloride process can occur in the aggregate state by avoiding the
), chloroacetyl chloride (ClCH
COCl), oxalyl chloride destruction of intramolecular hydrogen bonds by polar solvent.
, and triphosgene to the test solution of APQ.
3
(SO
COCl)
2
Cl
2
2
(
2
3
.2 Study of the solvent effect of APQ to phosgene
2
.4 Phosgene sensing with filter paper
Next, we screened the solvent effect of the response of APQ to
phosgene. APQ has significant differences in response to
A piece of filter paper was cut to 1 ꢀ 3 cm and immersed in the
APQ solution (50 mM in CH CN) for 10 seconds, then taken out
3
and dried in air. In the test, the resultant paper strips
embedded with the probe APQ were placed in sealed flasks
(
1
250 mL). Different triphosgene concentrations (0.1 mL of 0,
.5, 3.0, and 6.0 mg mL triphosgene in CH CN) were added to
3
ꢁ
1
the flasks followed by injection of two equivalents of TEA.
Calculated from the amount of phosgene added, the concen-
tration of gaseous phosgene in the sealed flask was estimated
ꢁ1
as the following: 0, 1.2, 2.4, and 4.8 mg L , respectively. After
minute, the paper strips were taken out and photographed
under a portable 365 nm UV light lamp.
1
3. Results and discussion
As shown in Scheme 2, the probe APQ can be easily prepared in
two steps under comfortable conditions, starting from the
commercial reagents 2-aminobenzamide and 2-nitrobenzal-
dehyde, with high yield. The product (APQ) was well characterized
1
13
by H, and C NMR (ESI†).
3.1 AIE properties of APQ
With the probe in hand, we firstly evaluated the AIE character-
istics of APQ by measuring the fluorescence emission spectra
Fig. 1 (a) Fluorescence spectra of APQ in acetonitrile and acetonitrile/
water mixtures with different water fractions (f
62 nm. (b) Plot of relative fluorescence intensity (I/I
versus the solvent composition of acetonitrile/water mixture. Inset:
w
%); [APQ] = 10 mM; lex
=
3
0
) of APQ at 447 nm
Scheme 2 Synthesis of APQ: (a) EtOH, CuCl
Pd/C, H , ethanol/dioxane (1 : 1), r.t., 24 h, 59%; (c) triphosgene, TEA,
dioxane, r.t., 30 min, 75%.
2
, reflux, 16 h, 56%; (b) 10%
2
2
Photographs of APQ in acetonitrile and H O/acetonitrile (99 : 1, v/v) taken
under UV light (365 nm).
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2021
New J. Chem., 2021, 45, 5631–5636 | 5633

View Article Online
Paper
NJC
phosgene in four aprotic solvents commonly used for phosgene 3.4 Study on the time response of APQ to phosgene
tests, namely chloroform, THF, acetonitrile, and dioxane
Since the fluorescent response dynamics of a probe is an
(Fig. S1, ESI†). Compared with THF and dioxane, APQ has
important parameter for qualitative analyte detection in real-
time, the time-dependent fluorescence response of APQ in the
presence of phosgene was investigated (Fig. 3 and Fig. S4, ESI†).
As we expected, APQ hardly reacted with triphosgene (10.0 mM)
in the absence of TEA. Upon adding triphosgene (10.0 mM) to a
better solubility in chloroform and CH CN, so APQ has almost
3
no fluorescence in these two solvents due to the free rotation
around single bonds. When phosgene was added to chloroform
or acetonitrile of APQ, it produced a 22-fold or 30-fold increase
in fluorescence, respectively. Therefore, we chose acetonitrile as
the test solvent in the subsequent experiments.
CH CN solution of APQ (10.0 mM), the fluorescence intensity at
3
4
1
61 nm reaches a plateau after 10 s and only increases about
.5-fold. However, with the further addition of TEA, the fluorescence
intensity of the solution of APQ rapidly increased 22-fold within
0 seconds. These results indicate that APQ can respond
specifically to phosgene instead of triphosgene.
3.3 Study of the spectroscopic properties of APQ to phosgene
2
Subsequently, the UV-Vis absorption spectra and fluorescence
emission spectra of APQ and APQ titrated with phosgene were
3
tested in CH CN (containing 1% TEA). APQ alone has a
moderate absorption in the range of 350–400 nm, and this
absorption band increases slightly after adding phosgene
3
.5 Study on the selectivity of sensing phosgene
The selectivity is an important parameter to evaluate whether a
fluorescent probe can be used for analyte detection. Next,
fluorescence titration of APQ with various common acid chlorides
was performed to assess its selectivity (Fig. 4). To our delight, the
fluorescence response of APQ is highly specific to phosgene.
Using a variety of common competitive acid chlorides (including
thionyl chloride (SOCl2), phosphorus oxychloride (POCl3),
p-toluene sulfonyl chloride (TosCl), diethyl chlorophosphate
(Fig. S2, ESI†). Just as expected, due to the free rotation of
2-aminophenyl of APQ in the tested solution, APQ alone is
almost non-fluorescent (lex = 377 nm, F = 0.009, Table S1,
ESI†). However, with the gradual addition of phosgene, a new
fluorescence emission band centered at 447 nm appeared and
increased rapidly (Fig. 2). The solution changes from colorless
to blue, attributed to the formation of new restricted
intramolecular motion products APQU1 (see Scheme 1). Also,
the fluorescence titration curve shows that as the phosgene
(DCP), acetyl chloride (CH COCl), sulfonyl chloride (SO Cl ),
3
2
2
2 2
chloroacetyl chloride (ClCH COCl), oxalyl chloride (COCl) , and
triphosgene), no apparent changes in fluorescence emission were
observed (Fig. 4 and Fig. S5, ESI†).
2
concentration increases (in the range of 0–4.0 mM, R = 0.98,
Fig. S3, ESI†), the fluorescence intensity at 461 nm increases
linearly, and further steadily increases until it reaches the
maximum value of 10.0 mM of phosgene.
Based on these results, the calculated APQ detection limit of
phosgene is 0.16 ppm (based on 3d/k), which is lower than
As mentioned above, many reported phosgene fluorescent
probes usually respond to triphosgene to some extent.
Fortunately, under the test conditions, the probe APQ has
almost no observable fluorescence response to triphosgene.
Moreover, subsequent competition experiments showed that
APQ is still highly sensitive to phosgene even in the presence of
the above-mentioned competing acid chlorides (Fig. S6 and S7,
ESI†). Therefore, these results indicate that the probe APQ is
highly selective for phosgene and can be used for the specific
detection of phosgene.
2
ppm, the threshold of the immediate danger to health and
4
life by phosgene (IDLH). These results indicate that the probe
APQ could be used as a sensitive fluorescent probe for the
quantitative detection of phosgene in solution.
Fig. 2 Fluorescence spectra of APQ (10.0 mM) in CH
(
(
3
CN solution
containing 1% TEA) in the presence of different concentrations of phosgene
0–2.0 equiv.) (lex = 377 nm). Top inset: The fluorescence intensity of APQ
Fig. 3 Time-dependent response in the fluorescence intensity at 461 nm
at 461 nm (I461) as a function of phosgene concentration (0–2.0 equiv.).
Bottom inset: Cuvette images of probe APQ before and after addition of
phosgene taken under a hand-held UV lamp (lex = 365 nm).
3
for the solutions of probe APQ (10.0 mM) in CH CN solution, followed by
addition of triphosgene (10.0 mM) for 100 s, and then the addition of TEA
(10.0 mM) for another 200 s (lex = 377 nm).
5634
|
New J. Chem., 2021, 45, 5631–5636
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2021

View Article Online
NJC
Paper
Fig. 5 Photographs of the fluorescence of test strips containing absorbed
probe APQ exposed for 1 min to vapors containing various amounts of
ꢁ
1
ꢁ1
phosgene in the flask, (1) 0; (2) 1.2 mg L of phosgene gas; (3) 2.4 mg L
ꢁ1
of phosgene gas; (4) 4.8 mg L of phosgene gas (under a 365 nm hand-
held UV lamp).
the calculated molecular weight of fused APQ-urea products
+
13
[
M + H] (calcd. 264.0768 for C H N O ). Surprisingly, the
C
1
5
10 3 2
NMR spectrum of the reaction product of APQ and phosgene
showed that the chemical shift of the amide carbonyl group was
166.4 ppm (Fig. S10, ESI†), which indicated that the product
3
Fig. 4 Fluorescence intensity in 461 nm (I461) of a CH CN solution of
probe APQ (10.0 mM) before and after addition of various analytes
2
including SOCl , POCl , TosCl, DCP, AcCl, SO Cl , ClCH COCl, (COCl) ,
(
2
3
2
2
2
1
9
triphosgene, and phosgene, (lex = 377 nm, slits: 5/5 nm)); Top inset: was APQU1 instead of APQU2. On this basis, we propose a
3
Cuvette images of CH CN solutions of probe APQ before and after addition
new APQ response mechanism to phosgene. The nitrogen atom
in APQ first undergoes a nucleophilic substitution reaction with
of different analytes taken under a UV hand-held lamp (lex = 365 nm).
ꢁ
phosgene to remove Cl to form intermediate N-oxychloride II
(
Scheme 3, pink part). The intermediate II then undergoes an
3
.6 Plausible sensing mechanism
intramolecular nucleophilic substitution reaction to transfer the
We propose that the sensing of phosgene by the probe APQ
starts with nucleophilic substitution by the nitrogen atom with
the removal of HCl to form the intermediate N-oxychloride
0
+
oxychloride to the 2 -amine group and then releases H to form
the N-oxychloride intermediate III. Finally, the intermediate III
undergoes a further intramolecular nucleophilic substitution to
(Scheme 3, gray part). The intermediate N-oxychloride under-
0
remove HCl, forming 3, 2 -fused APQ-urea product APQU1.
goes an intramolecular nucleophilic substitution reaction to
ꢁ
+
remove Cl followed by the release of H , thereby forming a 3.7 Detection of phosgene vapor
0
1,2 -fused APQ-urea product APQU2 (Scheme 3, gray part).
Finally, based on the excellent response of APQ to phosgene in
solution, we also used a simple test strip experiment to inves-
tigate the practicability of the probe APQ for gaseous phosgene
detection. To this end, the test paper strips were immersed in
acetonitrile solution of APQ, and after drying, the APQ-loaded
test strips were obtained. As shown in Fig. 5, the APQ-loaded
test strip shows green emission under a 365 nm handheld UV
lamp due to the AIE effect in APQ molecules in the solid-state.
However, after the test strips were exposed to gaseous phos-
gene, as the phosgene concentration gradually increased from 0
1
Then, the H NMR titration experiment was carried out to
obtain evidence for the proposed mechanism. As shown in
Fig. S8 (ESI†), the characteristic resonances for the 2 -amino
group (H-7 ) and amide (H-3) protons of APQ were at 7.08 (2H, s)
and 12.14 (1H, s) ppm, respectively. Upon the addition of phos-
gene (by the addition of 1.0 equiv. of triphosgene and 2.0 equiv. of
0
0
0
TEA), the peaks at 7.08 ppm attributed to H-7 decreased and
downfield shifted to 10.86 (1H, s) ppm. Meanwhile, the peak at
12.14 ppm attributed to H-3 vanished entirely. Moreover, the
formation of the fused APQ-urea product promoted a downfield
shift of the aromatic proton resonances. This result indicates that
the fused APQ-urea compound has been produced by the reaction
of APQ and phosgene.
An ESI-MS experiment was also conducted to verify the
formation of fused APQ-urea products (Fig. S9, ESI†).
ꢁ1
to 4.8 mg L , the color of the fluorescence gradually changed
from green to blue, indicating that APQ reacted with phosgene
to form APQU1. Those results show that the probe APQ has the
ability to detect phosgene in the gas phase with high sensitivity.
The mixture showed a major peak at m/z 264.0771, matching 4. Conclusions
In summary, we developed an APQ-based fluorescent
chemosensor APQ, which can selectively detect phosgene over
triphosgene, various nerve gases, and acid chlorides. Owing to
the specific cyclization reactions, APQ exhibits an obvious
fluorescence turn-on response at 461 nm toward phosgene with
large Stokes shift (104 nm), instant response (less than 20 s),
and a low detection limit (0.16 ppm). Finally, based on the AIE
effect of APQ, the APQ-loaded test strip was prepared and
demonstrated to have practical utility in the detection of
phosgene vapor.
Scheme 3 Proposed mechanism of the APQ response to phosgene.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2021
New J. Chem., 2021, 45, 5631–5636 | 5635

View Article Online
Paper
NJC
Conflicts of interest
J. L. Sessler and T. D. James, Chem. Soc. Rev., 2020, 49,
5110–5139; ( f ) S.-H. Park, N. Kwon, J.-H. Lee, J. Yoon and
There are no conflicts to declare.
I. Shin, Chem. Soc. Rev., 2020, 49, 143–179; (g) H. Xiao, P. Li
and B. Tang, Coordin. Chem. Rev., 2021, 427, 213582;
(
h) S. Y. Park, S. A. Yoon, Y. Cha and M. H. Lee, Coordin.
Acknowledgements
Chem. Rev., 2021, 428, 213613; (i) Y. Liu, Y. Yu, Q. Zhao,
C. Tang, H. Zhang, Y. Qin, X. Feng and J. Zhang, Coordin.
Chem. Rev., 2021, 427, 213601.
5 (a) W.-Q. Zhang, K. Cheng, X. Yang, Q.-Y. Li, H. Zhang,
Z. Ma, H. Lu, H. Wu and X.-J. Wang, Org. Chem. Front., 2017,
This work was supported by the Zhejiang Provincial Natural
Science Foundation of China (Grant No. LY17B070008), the
Zhejiang Postdoctoral Research Fund (No. ZJ20180020), the
Zhejiang Sci-Tech University Research Fund (No. 15062174-Y),
and the Project Grants 521 Talents Cultivation of Zhejiang Sci-
Tech University.
1
4
, 1719–1725; (b) H.-C. Xia, X.-H. Xu and Q.-H. Song, ACS
Sens., 2017, 2, 178–182; (c) H. Xie, Y. Wu, F. Zeng, J. Chen
and S. Wu, Chem. Commun., 2017, 53, 9813–9816;
(
2
d) L. Chen, D. Wu, J.-M. Kim and J. Yoon, Anal. Chem.,
017, 89, 12596–12601; (e) W. Feng, S. Gong, E. Zhou, X. Yin
Notes and references
1
2
3
4
M. Prentiss, Chemicals in War, McGraw-Hill, New York,
937, pp. 216–217.
B. Bast and D. F. Glass-Mattie, Handbook of Toxicology of Chemical
Warfare Agents, R. C. Gupta, Academic Press, Boston, 2015.
S. A. Cucinell and E. Arsenal, Arch. Environ. Health, 1974, 28,
and G. Feng, Anal. Chim. Acta, 2018, 1029, 97–103;
( f ) T. Cao, D. Gong, L. Zheng, J. Wang, J. Qian, W. Liu,
Y. Cao, K. Iqbal, W. Qin and A. Iqbal, Anal. Chim. Acta, 2019,
1078, 168–175; (g) L. Yang, Z. Sun, Z. Li, X. Kong, F. Wang,
X. Liu, J. Tang, M. Ping and J. You, Anal. Methods, 2019, 11,
4600–4608; (h) K. Maiti, D. Ghosh, R. Maiti, V. Vyas,
P. Datta, D. Mandal and D. K. Maiti, J. Mater. Chem. A,
2019, 7, 1756–1767; (i) S.-L. Wang, C.-L. Zhang and
Q.-H. Song, J. Mater. Chem. C, 2019, 7, 1510–1517;
( j) L. Zeng, H. Zeng, L. Jiang, S. Wang, J.-T. Hou and
J. Yoon, Anal. Chem., 2019, 91, 12070–12076; (k) Q. Hu,
Q. Huang, K. Liang, Y. Wang, Y. Mao, Q. Yin and H. Wang,
Dyes Pigm., 2020, 176, 108229; (l) S. Wang, B. Zhu, B. Wang,
P. Fan, Y. Jiu, M. Zhang, L. Jiang and J.-T. Hou, Dyes Pigm.,
2020, 173, 107933; (m) L. Yang, F. Wang, Z. Sun, X. Kong
and Y. Kong, Anal. Methods, 2020, 12, 3123–3129;
(n) L. Patra, K. Aich, S. Gharami and T. K. Mondal, Sens.
Actuators, B, 2021, 326, 128837; (o) L. Yang, F. Wang, J. Zhao,
X. Kong, K. Lu, M. Yang, J. Zhang, Z. Sun and J. You,
Talanta, 2021, 221, 121477; (p) L. Bai, W. Feng and
G. Feng, Dyes Pigm., 2019, 163, 483–488; (q) K. Cheng,
N. Yang, Q. Li, X. Gao and X. Wang, ACS Omega, 2019,
4(27), 22557–22561.
1
272–275.
U.S. National Institute for Occupational Safety and Health
NIOSH Pocket Guide to Chemical Hazards, Publication 97-
1
40, NIOSH, Washington, DC, 2005.
E. D. Robin, C. E. Cross and R. Zelis, N. Engl. J. Med., 1973,
88, 292–304.
5
6
2
W. W. Holmes, B. M. Keyser, D. C. Paradiso, R. Ray,
D. K. Andres, B. J. Benton, C. C. Rothwell, H. M. Hoard-
Fruchey, J. F. Dillman, A. M. Sciuto and D. R. Anderson,
Toxicol. Lett., 2016, 244, 8–20.
S. C. Gad, Encyclopedia of Toxicology, Academic Press,
Oxford, 2014, pp. 904–906.
A. Watson, D. Opresko, R. A. Young, V. Hauschild, J. King
and K. Bakshi, Handbook of Toxicology of Chemical Warfare
Agents, Academic Press, Boston, 2015, 87–109.
J. Beheshtian, A. A. Peyghan and Z. Bagheri, Sens. Actuators,
B, 2012, 171, 846–852.
7
8
9
1
1
1
1
1
0 R. J. Rando, H. G. Poovey and S. N. Chang, J. Liq. Chroma-
togr., 1993, 16, 329–349.
1 W. B. Crummett and J. D. McLean, Anal. Chem., 1965, 37,
16 (a) T. Kim, B. Hwang, J. Bouffard and Y. Kim, Anal. Chem.,
2017, 89, 12837–12842; (b) M. Du, B. Huo, J. Liu, M. Li,
A. Shen, X. Bai, Y. Lai, L. Fang and Y. Yang, J. Mater. Chem.
C, 2018, 6, 10472–10479; (c) Y.-L. Huang, W. Ye, Y.-T. Su,
Z.-Y. Wu and H. Zheng, Dyes Pigm., 2020, 173, 107854;
(d) B. Ma, X. Wang, S. Gao, L. Qi, Y. Xu, J. Yang and
G. Zuo, Dyes Pigm., 2020, 177, 108279; (e) S. Paul,
P. Ghosh and P. Roy, New J. Chem., 2020, 44, 5784–5791.
424–425.
2 N. Nakano, A. Yamamoto, Y. Kobayashi and K. Nagashima,
Talanta, 1995, 42, 641–645.
3 S. Virji, R. Kojima, J. D. Fowler, J. G. Villanueva, R. B. Kaner
and B. H. Weiller, Nano Res., 2009, 2, 135–142.
4 For reviews see: (a) J. L. Kolanowski, F. Liu and E. J. New,
Chem. Soc. Rev., 2018, 47, 195–208; (b) A. Aliyan, N. P. Cook 17 M. Gao, S. Li, Y. Lin, Y. Geng, X. Ling, L. Wang, A. Qin and
and A. A. Marti, Chem. Rev., 2019, 119, 11819–11856; B. Z. Tang, ACS Sens., 2016, 1, 179–184.
c) Y. Yue, F. Huo, F. Cheng, X. Zhu, T. Mafireyi, 18 (a) J. Mei, Y. Hong, J. W. Y. Lam, A. Qin, Y. Tang and
(
R. M. Strongin and C. Yin, Chem. Soc. Rev., 2019, 48,
B. Z. Tang, Adv. Mater., 2014, 26, 5429–5479; (b) J. Mei,
N. L. C. Leung, R. T. K. Kwok, J. W. Y. Lam and B. Z. Tang,
Chem. Rev., 2015, 115, 11718–11940.
4155–4177; (d) X. Liu, N. Li, M. Li, H. Chen, N. Zhang,
Y. Wang and K. Zheng, Coordin. Chem. Rev., 2020,
404, 213109; (e) L. Wu, C. Huang, B. P. Emery, 19 J. Bergman, C.-J. Arewang and P. H. Svensson, J. Org. Chem.,
A. C. Sedgwick, S. D. Bull, X.-P. He, H. Tian, J. Yoon, 2014, 79, 9065–9073.
5636
|
New J. Chem., 2021, 45, 5631–5636
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2021