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Fluorescent chemosensor for dual-channel discrimination between phosgene and triphosgene Shaolin Wang, Chen Li, and Qin-Hua Song Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.8b05777 • Publication Date (Web): 17 Apr 2019 Downloaded from http://pubs.acs.org on April 17, 2019
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Analytical Chemistry
Fluorescent chemosensor for dual-channel discrimination between phosgene and triphosgene Shao-Lin Wang, Chen Li and Qin-Hua Song* Department of Chemistry, University of Science and Technology of China, Hefei 230026, P. R. China. *E-mail:
[email protected] ABSTRACT: As highly toxic and accessible chemical reagents, phosgene and triphosgene have become serious threat to public safety. So, it is highly desirable to develop facile methods to detect and recognize them. In this Article, a novel fluorescent chemosensor, Phos-4, has been constructed with 1,8-naphthalimide as the fluorophore and 2-(2-aminophenyl)imidazol as the recognition sites for discrimination between phosgene and triphosgene in dual-channel mode for the first time. Owing to the difference in electrophilicity between chlorocarbonyl and trichloromethoxycarbonyl, the sensing reaction of Phos-4 with phosgene undergoes twice carbamylations to afford a cyclic product with green fluorescence, and only once carbamylation occurs for triphosgene to form non-cyclic product with blue fluorescence. The sensor Phos-4 exhibits high sensitivity (the limit of detection, 3.2 nM for phosgene and 1.9 nM for triphosgene) and high selectivity in solutions. Furthermore, a facile test papers containing Phos-4-embedded nanofibrous membrane have been fabricated by the electrospinning technology. The test papers can provide visual and selective detection of phosgene with a lower limit of detection (42 ppb) and a faster response ( 10 s) in gas phase over those in solutions. The test paper with Phos-4 is promising to be a practical detection tool of gaseous phosgene.
Phosgene is a highly poisonous colorless gas, and causes pulmonary edema, respiratory failure, and even death, used as a chemical warfare agent (CWA) during the World War I.1,2 In comparison with other strictly controlled CWAs such as nerve agents (Tabun, Soman and Sarin),3 phosgene is accessible in the chemical industry.4 As a cost-effective and solid substitute for phosgene, triphosgene is widely used in organic synthesis,5 and be easily translated into phosgene in the presence of nucleophiles (e.g., chloride ion, tertiary amines).7, 8 For this reason, both phosgene and triphosgene have been potential threat to public safety because of their wilful use in terroristic activities and unexpected leakage during industrial accidents.9 Thus, it is urgent to develop facile methods for their detection and recognization. Compared with routine methods that need tedious sample pretreatment or expensive instrumentation,10-13 fluorescent chemosensors offer some unique advantages, such as high sensitivity and selectivity, simplicity for manipulation, short response time and low detection limit. So far, almost twenty fluorescent chemosensors have been developed for detection of phosgene and its substitutes.14 Owing to the bifunctional and electrophilic characters of phosgene and triphosgene, most of sensors were designed to contain two nucleophilic groups (e.g., amino, imino and hydroxyl), and can undergo successive twice carbamylations to lead to heterodimerization15 or intramolecular cyclization,1634 giving rise to spectral changes resulting from different mechanisms including ICT,20-22, 27-29, 32, 34 photoinduced electron transfer (PET),18, 19, 23, 24, 30, 31 fluorescence resonance energy transfer (FRET),15 excited state intramolecular proton transfer (ESIPT),25, 33 aggregation-induced emission (AIE),26 spirocyclic ring opening16, 18 and coumarin forming,17 and these sensors were summarized in Table S1 as Supporting Information. Among them, only a few sensors are capable of
discrimination between phosgene and triphosgene, and classified into two types. As shown in Scheme 1a, the sensors can react with both phosgene and triphosgene,21, 22, 24, 25, 28, 29, 34 and display less fluorescent response to triphosgene than phosgene during a short analysis time due to their different sensing rates. A long analysis time of triphosgene would lead to similar fluorescent response with phosgene. For sensor II shown in Scheme 1b, they can react only with phosgene, but not with triphosgene.23, 31 In other words, sensors II can respond to phosgene, but cannot give any signal to triphosgene. Hence, it is highly admirable to develop a new type of fluorescent chemosensor, sensor III (Scheme 1c), which is not only able to respond to both phosgene and triphosgene, but also discriminate between them by different fluorescence signals. To the best of our knowledge, this sensor has been reported. Scheme 1. Response models of sensors for discrimination between phosgene and triphosgene in previous works (a, b) and this work (c). (a)
(b) slow
Sensor
(c) Sensor
f ast
Sensor
Cl Cl
Cl
O O
Cl O
Cl Cl
(triphosgene) O Cl
Cl
(phosgene)
Scheme 2. Chemical structures of the sensor Phos-4 and
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proposed sensing triphosgene. n
O
mechanisms
to
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n
Bu N
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new ICT
N
N HN
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O Cl3CO
n
Bu N
O
OCCl3
Cl N EtO
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Bu N
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new ICT Cl
O
N
O EtO
O
O
ICT
OCCl3
and
Phos-4
N
NH2
N
N
EtO
1
In this work, we selected 1,8-naphthalimide unit as the fluorophore and 2-(2-aminophenyl)imidazol as the reactive sites, and constructed a novel fluorescent chemosensor, Phos-4. As shown in Scheme 2, Phos-4 reacts with phosgene to yield the cyclic product 1 via twice carbamylations, and only once carbamylation to produce a proposed sensing product 2 for triphosgene, giving different fluorescence responses resulting from different character of intramolecular charge transfer (ICT), thereby, achieving a dual-channel discrimination between phosgene and triphosgene. In addition, new insights into the difference in their reactivity were gained from the sensing reactions of Phos-4 with phosgene and triphosgene.
■ EXPERIMENTAL SECTION Materials and General Methods. All chemicals for synthesis were purchased from commercial suppliers and were used as received without further purification. 1H and 13C NMR spectra were measured in CDCl3 or DMSO-d6 with a Bruker AV spectrometer operating at 400 MHz and 100 MHz, respectively and chemical shifts were reported in ppm using tetramethylsilane (TMS) as the internal standard. Mass spectra were obtained with a Thermo LTQ Orbitrap mass spectrometer or MALDI-TOF. UV-vis absorption and fluorescence emission spectra were recorded with a Shimadzu UV-2450 UV/vis spectrometer and a Shimadzu RF-5301PC Luminescence Spectrometer, respectively. Synthesis and Characterization Synthesis of 9-(2aminophenyl)-5-butyl-10-(2ethoxyethyl)benzo[de]imidazo[4,5-g]isoquinoline4,6(5H,10H)-dione (Phos-4). Phos-229 (355 mg, 1.0 mmol) and H2O (4 mL) were dissolved in DMF (16 mL), then 2nitrobenzaldehyde (181 mg, 1.2 mmol) was added followed by oxone (739 mg, 1.2 mmol). The mixture was stirred for 1 h at 70C after which TLC analysis indicated complete reaction. After natural cooling, the reaction mixture was added dropwise with vigorous stirring into H2O (60 mL). In cases where the crude product precipitated, it was collected by filtration, washed with H2O and dried. Without further purification, the crude product, FeCl3•6H2O (27 mg, 0.1 mmol) and activated carbon (50 mg) were added into CH3OH (15 mL), then heated at 70C for 10 min under N2, then N2H4•H2O (85%, 0.5 mL) was added dropwise. After being heated at 70C for another 1 h, the mixture was cooled down to room temperature, filtrate was collected by using kieselguhr (filter aids) and water (40 mL) was added into the filtrate and extracted with CH2Cl2 (20 mL 3). The organic extracts were collected, washed with brine (50 mL), dried over anhydrous Na2SO4, filtered, and evaporated to give the crude product. The crude product was purified by column chromatography to give the target product Phos-4 (333 mg, yield 73 %) as a yellow solid. Rf = 0.30 (CH2Cl2/EtOAc = 10:1, v/v). 1H NMR (400 MHz, CDCl3, 25°C, TMS): δ = 8.99 (s, 1H, Ar-H), 8.67
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(d, J = 8.4 Hz, 1H, Ar-H), 8.61 (d, J = 7.2 Hz, 1H, Ar-H), 7.82 (t, J = 8.0 Hz, 1H, Ar-H), 7.40 (d, J = 7.2 Hz, 1H, Ar-H), 7.32 (t, J = 7.8 Hz, 1H, Ar-H), 6.89 (m, 2H, Ar-H), 4.84 (t, J = 6.2 Hz, 2H, CH2), 4.20 (t, J = 7.2 Hz, 2H, CH2), 3.83 (t, J = 6.0 Hz, 2H, CH2), 3.32 (q, J = 6.8 Hz, 2H, CH2), 1.75 (m, 2H, CH2), 1.47 (m, 2H, CH2), 1.01 (m, 6H, CH3 2) ppm; 13C NMR (100 MHz, CDCl3, 25°C, TMS): δ = 164.46, 164.19, 154.44, 146.85, 140.56, 132.96, 131.46, 130.79, 128.81, 126.50, 126.46, 126.36, 126.26, 123.74, 120.37, 118.10, 117.96, 116.70, 113.61, 68.27, 66.88, 46.62, 40.41, 30.20, 20.43, 14.86, 13.86 ppm; HRMS (ESI-TOF) m/z: calcd for C27H29N4O3: 457.2234, found: 457.2224 [M + H+]. Synthesis of 10-butyl-15-(2-ethoxyethyl)-6Hbenzo[4',5']isoquinolino[6',7':4,5]imidazo[1,2-c]quinazoline6,9,11(10H,15H)-trione (1). Phos-4 (46 mg, 0.1 mmol) and triethylamine (0.1 mL) were dissolved in dry CH2Cl2 (10 mL) at 0C under N2, then added to dry CH2Cl2 (1 mL) with triphosgene (30 mg, 0.1 mmol) over a period of 10 min. The mixture was stirred for another 20 min at 0C after which TLC analysis indicated complete reaction. NaOH aqueous solution (0.05 N, 20 mL) was added into the mixture and extracted with CH2Cl2 (20 mL 2). The organic extracts were collected, washed with brine (30 mL), dried over anhydrous Na2SO4, filtered, and evaporated to give the crude product. The crude product was mixed with ether (5 mL), and then the mixture was filtered and washed with ether (5 mL 3). The solid residue was dried in a 30C vacuum oven to give the compound 1 (42 mg, yield 87 %) as a yellow solid. 1H NMR (400 MHz, CDCl3, 25°C, TMS): δ = 9.59 (s, 1H, Ar-H), 9.09 (d, J = 8.8 Hz, 1H, Ar-H), 8.71 (d, J = 7.2 Hz, 1H, Ar-H), 8.17 (d, J = 8.4 Hz, 1H, CH), 8.09 (t, J = 8.0 Hz, 1H, Ar-H), 7.35 (t, J = 8.0 Hz, 1H, CH), 7.12 (t, J = 7.6 Hz, 1H, CH), 7.02 (d, J = 8.4 Hz, 1H, CH), 5.58 (t, J = 5.6 Hz, 2H, CH2), 4.49 (t, J = 5.6 Hz, 2H, CH2), 3.85 (t, J = 7.6 Hz, 2H, CH2), 3.63 (q, J = 7.2 Hz, 2H, CH2), 1.61 (m, 2H, CH2), 1.40 (m, 2H, CH2), 1.12 (t, J = 7.2 Hz, 3H, CH3), 0.98 (t, J = 7.6 Hz, 3H, CH3) ppm; 13C NMR (100 MHz, CDCl3, 25°C, TMS): δ = 163.1, 162.1, 145.9, 134.3, 131.4, 130.3, 128.5, 128.1, 126.8, 126.2, 126.1, 124.6, 123.5, 123.2, 121.4, 120.6, 120.0, 118.4, 104.1, 67.7, 67.6, 49.1, 40.4, 30.0, 20.3, 14.9, 13.8 ppm; HRMS (ESI-TOF) m/z: calcd for C28H27N4O4: 483.2027, found: 483.2021 [M + H+]. Synthesis of N-(2-(5-butyl-10-(2-ethoxyethyl)-4,6-dioxo4,5,6,10-tetrahydrobenzo[de]imidazo[4,5-g]isoquinolin-9yl)phenyl)acetamide (3). Phos-4 (91 mg, 0.2 mmol) and TEA (0.2 mL) were dissolved in dry CH2Cl2 (10 mL) at 0C under N2, then CH3COCl (18 μL, 0.25 mmol) was added dropwise. The mixture was stirred for 0.5 h at 0C after which TLC analysis indicated complete reaction. H2O (20 mL) was added into the solutions and extracted with CH2Cl2 (20 mL 2). The organic extracts were collected, washed with brine (30 mL), dried over anhydrous Na2SO4, filtered, and evaporated to give the crude product. The crude product was purified by column chromatography to give the compound 3 (82 mg, yield 82 %) as a yellow solid. Rf = 0.42 (CH2Cl2/EtOAc = 6:1, v/v). 1H NMR (400 MHz, DMSO-d6, 25°C, TMS): δ = 9.76 (br s, 1H, NH), 8.85 (d, J = 8.4 Hz, 1H, Ar-H), 8.62 (s, 1H, Ar-H), 8.46 (d, J = 7.6 Hz, 1H, Ar-H), 7.93 (m, 1H, Ar-H), 7.84 (d, J = 8.0 Hz, 1H, Ar-H), 7.68 (d, J = 7.6 Hz, 1H, Ar-H), 7.57 (t, J = 8.0 Hz, 1H, Ar-H), 7.35 (t, J = 7.6 Hz, 1H, Ar-H), 4.73 (t, J = 5.2 Hz, 2H, CH2), 4.00 (q, J = 7.2 Hz, 2H, CH2), 3.73 (t, J = 5.2 Hz, 2H, CH2), 3.12 (q, J = 7.2 Hz, 2H, CH2), 1.97 (s, 3H, COCH3), 1.63 (m, 2H, CH2), 1.37 (m, 2H, CH2), 0.94 (t, J =
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Analytical Chemistry 7.2 Hz, 3H, CH3), 0.84 (t, J = 7.2 Hz, 3H, CH3) ppm; 13C NMR (100 MHz, DMSO-d6, 25°C, TMS): δ = 169.02, 163.95, 163.60, 154.54, 140.62, 137.59, 133.18, 132.20, 131.01, 128.77, 128.03, 127.35, 125.64, 125.47, 124.82, 123.11, 122.69, 120.41, 117.35, 67.91, 66.03, 46.61, 30.08, 23.90, 20.29, 15.12, 14.17 ppm; HRMS (ESI-TOF) m/z: calcd for C29H31N4O4: 499.2340, found: 499.2336 [M + H+]. Assay Experiments. In all the experiments, triphosgene is employed to generate phosgene in situ in the presence of triethylamine (TEA),35-37 avoiding direct use of high toxic gaseous phosgene. Unless otherwise mentioned, 1,4-dioxane is employed as the solvent. To quantify phosgene, it is assumed that 1 mol triphosgene is equal to 3 mol phosgene in the presence of TEA in solutions (molar ratio of triphosgene to TEA is 1:5, see Supporting Information). Detection of phosgene in solutions. Add 10 μL TEA solution (0-25 mM) into 2.5 mL Phos-4 solution and then add 10 μL triphosgene solution (0-5 mM) into above mixture, giving phosgene (0-60 μM). Molar ratio of triphosgene to TEA is set as 1:5. For example, 10 μL TEA solution (10 mM) is added into 2.5 mL Phos-4 solution, and followed by the addition of 10 μL triphosgene solution (2 mM). Thus, phosgene is 24 μM in this case. Detection of relevant analytes in solutions. For triphosgene: 10 μL of stock solution (5 mM) was added into 2.5 mL Phos-4 solution, giving 20 μM. For nitric oxide (NO): 70 μL NO gas solution (1.8 mM in water) was added into 2.5 mL Phos-4 solution, giving 50 μM. Other analytes including oxalyl chloride ((COCl)2), thionylchloride (SOCl2), sulfuryl chloride (SO2Cl2), phosphorus oxychloride (POCl3), hydrogen chloride (HCl), diethyl chlorophosphate (DCP) and diethyl cyanophosphonate (DCNP)): 10 μL stock solutions (12.5 mM) were added into 2.5 mL Phos-4 solution, giving 50 μM. Preparation of Phos-4-embedded nanofibers. Nanofibers were made by a proper modification according to the literatures.18, 38 Phos-4 (5.0 mg) and poly(ethylene oxide) (M.W. = 1,000,000) (0.4 g) were dissolved in CH3CN (15 mL), and the resulting solution was loaded into a 10 mL syringe that was connected to an 7.0 kV voltage (EST705, high voltage generator). The flow rate of the solution was controlled at 1.0 mLh-1 by a syringe pump (PHD 2000 infusion, Harvard Apparatus), and the distance between needle and the grounded copper net was set to about 20 cm. And then the nanofibers were connected on the net. The fibers were carefully collected, dried in a 40C vacuum oven for 4-5 h, and then stored in a drier. The structures and morphologies of these fibers were observed by using electron microscopy (FE-SEM, JEOL JSM-6700F). Preparation of Phos-4 test paper. The electrospinning was carried out by placing a filter paper on the grounded copper net, and the filter paper covered with Phos-4-embedded fibrous membrane was obtained and dried in a 40C vacuum oven for 4-5 h. The above filter paper was cut into small strips (0.7 cm 1.4 cm) and then stored in a drier to work as the test paper for detection of phosgene and other analytes in gas phase. Detection of gaseous phosgene in various concentrations. Gaseous phosgene (0-50 ppm) in a sealed container was prepared by sequentially adding 20 μL TEA stock solution (00.25 mM, using CH2Cl2 as solvent) and 20 μL triphosgene stock solution (0-0.75 g/L, using CH2Cl2 as solvent) into a 75 mL bottle, and then quickly closing the lid. After 5 min, the
above mentioned Phos-4 test paper was moved into above bottle. 10 seconds later, the test paper was moved out from the phosgene atmosphere and then imaged under room light and 365 nm light, respectively. As an example, 20 μL TEA stock solution (0.1 mM) was added into a 75 mL bottle, and followed by the addition of 20 μL triphosgene stock solution (0.3 g/L), thus, the concentration of phosgene was calculated to be 20 ppm in this case, assuming that triphosgene was completely decomposed into gaseous phosgene. Detection of other analytes in gas phase. 2 mL analytical reagents (DCP, (COCl)2, SOCl2, SO2Cl2, POCl3, con. HCl, DCNP) were added into seven bottles (75 mL), respectively, and then saturating over 2 hours with tightly closed lids at room temperature. Using the same method for evaluating response to gaseous phosgene, the colorimetric and fluorescence change of Phos-4 test papers upon exposure to each analyte vapor for 5 seconds was observed and then imaged under room light and 365 nm light, respectively.
■ RESULTS AND DISCUSSION Synthesis of related compounds. As shown in Scheme 3, Phos-4 was synthesized with Phos-229 as a starting material by one-pot reaction in a total yield 73%, including two steps: i) cyclization/oxidation to form imidazole derivatives, ii) reduction of nitro group to form the amine. The proposed sensing product 1 was synthesized through twice carbamylation reactions between Phos-4 and triphosgene in the presence of TEA in a high good yield (87%). However, another proposed sensing product 2, which may be unstable, wasn’t isolated from the reaction of Phos-4 with triphosgene. As a comparison, compound 3 was prepared to mimic the sensing product 2 from the reaction of Phos-4 with acetyl chloride. The structures of Phos-4, compound 1 and 3 were fully characterized by 1H NMR, 13C NMR and high-resolution mass spectroscopy (HRMS). Scheme 3. Synthetic procedure of the sensor Phos-4, compound 1 and 3.a n
Bu
O
N
O
O n
n
Bu
O
N
O
O
Bu N
N
b)
O
N
N
87% a) NH2
EtO
73% N
NH EtO
Phos-2
1
N
EtO
NH 2
n
c)
Bu
O
N
O
82%
Phos-4
N N
O HN
3 EtO
a
Reagents and conditions: a) (i) 2-nitrobenzaldehyde, oxone, H2O/DMF, 70°C, 1 h; (ii) N2H4, FeCl3, active carbon, MeOH, 70°C, 1 h; b) triphosgene, TEA/CH2Cl2, 0°C, 0.5 h; c) CH3COCl, TEA/CH2Cl2, 0°C, 0.5 h.
Spectral response. The spectral responses toward phosgene and triphosgene were assessed by UV/vis absorption and fluorescence spectroscopies. First, the spectral response of Phos-4 toward triphosgene was observed. As shown in Figure 1ab, time-dependent UV/vis absorption and fluorescence spectra of Phos-4 solution upon the addition of triphosgene display a rapid absorption change with one isobestic points at
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Analytical Chemistry 285 nm, and a turn-on fluorescence centred at 422 nm, within 4 min, respectively. 0.4
400
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0 1 2 4
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Figure 1. Time-dependent (a) UV/Vis absorption and (b) fluorescence spectra of 10 μM Phos-4 solution upon addition of 20 μM triphosgene, (c) fluorescence spectra of 10 μM Phos-4 solution upon additions of 8 μM triphosgene and different concentrations of TEA (0-160 M), λex = 390 nm. 800
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80 40 0
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Figure 2. UV/vis absorption (a) and fluorescence spectra (b, c) of Phos-4 (10 μM) solution upon additions of different concentrations of phosgene (0-60 μM) or triphosgene (0-14 μM). Insets: calibration curve of fluorescence intensities as a function of [phogene] (b) or [triphosgene] (c), excitations at 390 nm for phosgene and 325 nm for triphosgene.
To optimize the amount of TEA for the generation of phosgene, fluorescence spectra of Phos-4 solution upon additions of triphosgene and different amounts of TEA (0-160 μM) in succession were recorded, shown in Fig 1c. Upon the addition of only triphosgene or a low concentration of TEA (8 μM), a turn-on fluorescence appears at 422 nm as a peak. When further additions of TEA (no less than 20 μM), a long wavelength fluorescence centred at 526 nm appears and increases, and then decreases at high concentrations, giving a maximum intensity at 40 M TEA (Inset of Fig. 1c), that is, the best ratio of triphosgene to TEA is 1:5. As the method of phosgene generation, the ratio of triphosgene to TEA was employed in all following experiments. Moreover, the change in fluorescence peaks from 422 nm to 526 nm reveal the formation of different sensing products in the sensing reactions with triphosgene (no TEA or low concentration of TEA) and with phosgene (no less than 20 M TEA). The next assessment of Phos-4 to phosgene was performed. Owing to too rapid rate of the reaction, not time- but dosedependent spectra of 10 M Phos-4 upon additions of phosgene (0-60 M) were shown in Figure 2. With increasing phosgene, remarkable absorbance changes were observed, decrease in the short-wavelength band (300-390 nm) and increase in the long-wavelength band (390-480 nm) with an isobestic point at 390 nm (Figure 2a). This observation shows
that the sensing reaction of Phos-4 to phosgene is single and effective. Meanwhile, the fluorescence spectra exhibit a remarkable turn-on response at 526 nm, ca. 420-fold (Figure 2b). Based on above fluorescence titration, the limit of detection (LOD) of Phos-4 can be obtained to be 3.2 nM for phosgene in terms of the equation of LOD = 3/k, where is the standard deviation of 15 times blank measurements, and k is the slope of the fitting straight line between the fluorescence intensity at 526 nm vs. the concentration of phosgene (Inset of Figure 2b). Similarly, the sensing property of Phos-4 toward triphosgene was evaluated under the same condition. Upon continuous additions of triphosgene, the fluorescence spectra display turn-on fluorescence mode, its peak at 422 nm, shown in Figure 2c. According the calibration curve (inset of Figure 2c), its LOD for triphosgene was calculated to be 1.9 nM. To assess the response time and the stability, the timedependent fluorescence intensity of Phos-4 before and after addition of phosgene was also recorded. As shown in Figure S1a, upon addition of phosgene, the fluorescence intensity at 526 nm increases gradually and reaches a plateau within 20 seconds. Thus, the response time and sensitivity of Phos-4 for detection of phosgene are superior to those of most reported fluorescent chemosensors (see Table S1). In addition, no obvious change was observed in fluorescence spectra under irradiation of 390 nm light for 2 h (Figure S1b), showing both Phos-4 and the sensing reaction system are photo- and
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Analytical Chemistry thermostable. Similar evaluation of Phos-4 to triphosgene was performed. A time-dependent fluorescence intensity at 422 nm reveals that the sensing reaction can finish within 2.5 min, shown in Figure S1c. Thus, the obvious difference in fluorescence peaks (526 nm vs. 422 nm) and response times (20 s vs. 2.5 min) would make Phos-4 to be a potential tool for discrimination between phosgene and triphosgene. The sensing mechanisms. To further clarify the sensing mechanism, the 1H NMR tracking experiment of the sensing reaction of Phos-4 with phosgene was performed by continuous measurements for four times. As shown in Figure 3, the peaks of chemical shifts at 9.02, 8.67, 8.60, 7.82, and 4.84 ppm were assigned to the proton H1, H2, H3, H4 and H5 of Phos-4 in CDCl3 containing TEA, respectively. After gradual additions of triphosgene, above proton signals disappear gradually and new signals appear at 9.54, 9.07, 8.70, 8.08 and 5.56 ppm, which are consistent with those of neat compound 1. Meanwhile, no peak of impurity was observed, indicating the transformation from Phos-4 to the expected product 1 was efficient. Moreover, HRMS was utilized to analyze the test solution treating Phos-4 with phosgene. The data of HRMS reveals two major peaks located at 457.2231 and 483.2017, which are consistent with the theoretical molecular weight of [Phos-4 + H]+ (457.2234) and [1 + H]+ (483.2027) as shown in Figure S2a. These results have demonstrated the plausible mechanism that Phos-4 reacts with phosgene to form product 1 via twice carbamylation reactions. n
O
O
O
Cl
Cl
N N
5
weak NG
4'
2' 3'
n
O
8.5
n
Bu N
8.0
a 6.0
5.5
O
O
N
Bu N
O
HN
2
5.0
Chemical shift /ppm
Figure 3. Partial 1 H NMR spectra of Phos-4 with TEA before (a) and after (b-e) additions of triphosgene for four times and (f) neat compound 1 in CDCl3.
In contrast, it is expected that Phos-4 can react with triphosgene to give mono-carbamylated product 2. HRMS provided the evidence for the sensing mechanism of Phos-4 toward triphosgene. As shown in Figure S2b, the peak at 617.08 is consistent with the theoretical molecular weight of [2 + H]+ (617.11). In addition, the acetylated compound 3 was chosen as a model of compound 2. Compound 3 (λmaxem = 424
N
weak EG
N
EtO
EtO
5
O N
OCCl3 O
b
9.0
strong EG
EtO
weak NG
c
9.5
O
very fast
OCCl3
N
d
4
Cl HN
2'
Cl3CO
5' e
23
N
O
f
1
weak NG N
Phos-4 slow
1
4'
O
Cl
strong NG
N
N
EtO
Phos-4
N
fast
NH2
EtO O
N
5'
Bu
O
1'
HCl
Cl
N
2'
NH2
O
O
N
N
3'
EtO
1'
N
O
O
1
n
Bu
Bu
N
2
n
O
n
Bu
3 4
nm) has the similar fluorescence spectrum with proposed 2 (λmaxem = 422 nm) from the reaction of Phos-4 with triphosgene, shown in Figure S3. In general, the nucleophilicity of organic bases can be weaken by electron-withdrawing group (EWG), reflecting in pKa values of some amines (Chart S1). Thus, the electronwithdrawing 1,8-naphthalimide unit reduces nucleophilicity of the nitrogen (Nsp2) of imidazol (Scheme 4). As shown in Scheme 4, because the primary amine (NH2) of aniline is a strong nucleophilic group (NG), Phos-4 is carbamylated at the primary amine by both phosgene and triphosgene to generate respectively an intermediate 2’ and product 2 in the first step. However, there is a significant difference in the reactivity between 2’ and 2 in the second step. The chlorocarbonyl is a stronger electrophilic group (EG) than 23 trichloromethoxycarbonyl.7, In other word, trichloromethoxide is not as good a leaving group as chloride. The former 2’ can undergo the intramolecular cyclization (the second carbamylation) to form the sensing product 1, and the latter 2 does not undergo second carbamylation. Scheme 4. Proposed sensing mechanism of Phos-4 toward phosgene and triphosgene.
1
Selectivity. To investigate the sensing specificity of Phos-4, the selectivity experiment was adopted by recording the fluorescence spectra, and the analytes include phosgene, triphosgene, (COCl)2, SOCl2, SO2Cl2, POCl3, HCl, NO, DCP and DCNP. As shown in Figure 4a, turn-on fluorescence responses of Phos-4 were observed for phosgene and triphosgene, no significant change for other analytes. By measuring fluorescence intensities at 526 nm and 422 nm, phosgene and triphosgene can be easily discriminated (Figure 4b). In particular, the sensing behavior can also be observed by the naked eyes under 365 nm light, shown in the inset of Figure 4b. The fluorescence color of Phos-4 solutions changes from non-fluorescence to green to phosgene and blue fluorescence toward triphosgene, no obvious fluorescence change for other analytes. Above observations exhibit that Phos-4 not only possesses high selectivity of phosgene and triphosgene over other analytes, but also can achieve a dualchannel discrimination between phosgene and triphosgene.
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Analytical Chemistry Detection of gaseous phosgene. To investigate the application of Phos-4, its response to phosgene in gas phase was evaluated. Electrospinning is an effective method to fabricate nano- and microfibrous membranes with a large surface areato-volume ratio and controlled morphology,39-41 affording the possibility to reduce the response time and enhance sensitivity.42, 43 For this reason, the polymer fibers containing Phos-4 were prepared from an electrospining system through jetting mixed solutions of poly(ethylene oxide) and Phos-4 in acetonitrile.
Intensity (a.u.)
450
triphosgene phosgene
a
300
150
blank & others 0 400
500
600
700
Wavelength /nm
To observe the morphology of Phos-4-embedded fibers before and after exposure to gaseous phosgene, scanning electron microscope (SEM) images were performed. As shown in Figure 5, the surface of the original nanofibers was smooth and their diameters were similar (ca. 0.9 μm). After exposure to gaseous phosgene, the diameters of the nanofibers became uneven. It is expected that the reaction of Phos-4 with phosgene in polymer matrixes occurs on the surface of nanofibers, resulting in some deformations of the original structures. Moreover, confocal microscope was utilized to image the fluorescence color of Phos-4-embedded nanofibers before and after exposure to gaseous phosgene. As shown in Figure 6, the nanofibers displayed no fluorescence emission collected from the green channel (450-600 nm) under 405 nm excitation. After exposure to phosgene, the relative emission intensity increased obviously. The merged images clearly show that the green fluorescence emits from the nanofibers. Moreover, through extending the time of electrospining, Phos-4embedded nanofibers can be knitted into fibrous membrane in a large scale. As shown in Figure S4, upon exposure to phosgene, the color and the fluorescence of membrane change from white and nonfluorescent to yellow and green fluorescent, which were easily observed by the naked eyes.
450
b Intensity (a.u.)
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300
@ 422 nm @ 526 nm
150
0
1 2 3 4 5 6 7 8 9 10 11 Analytes
Figure 4. (a) Fluorescence spectra and (b) fluorescence intensity at 422 nm (blue column)/526 nm (green column) of Phos-4 (10 μM) before (1) and after additions of (2) phosgene (30 μM), (3) triphosgene (20 μM) and other analytes (50 μM) in 1,4-dioxane after 4 min, (4) (COCl)2, (5) SOCl2, (6) SO2Cl2, (7) POCl3, (8) NO, (9) HCl, (10) DCP, (11) DCNP, λex = 390 nm. Inset: Photograph of above solutions under 365 nm light.
Figure 5. SEM images of Phos-4-embedded nanofibers before (a) and after (b) exposure to gaseous phosgene (1 ppm).
Figure 6. Confocal microscope images of Phos-4-embedded nanofibers before (a) and after (b) exposure to phosgene (1 ppm). The green channel fluorescence was collected from 450-600 nm, λex = 405 nm.
Above results indicate that the fibrous membrane containing Phos-4 is potentially valuable for the detection of phosgene in gas phase. So, a facile test paper was fabricated by the electrospinning. Briefly, placing filter papers (working as substrates) on the grounded copper net, and the filter papers cover with Phos-4-embedded fibrous membrane were obtained, and cut into strips to work as test papers. As shown in Figure 7, after exposure to various concentrations of phosgene (0-35 ppm, details see Table S2) for only 10 seconds, Phos-4 test papers change gradually from colorless and nonfluorescent to yellow and green fluorescent. Encouragingly, as low as 5 ppm phosgene can cause significant fluorescence change under 365 nm light. Both fast response and high sensitivity to phosgene gas make Phos-4 test paper superior to most chemosensors (see Table S1).
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Futhermore, above each test paper was analysed independently by using spectrofluorophotometer. As shown in Figure 8, the fluorescence intensity increased as the concentration of phosgene varied from 0 to 35 ppm, and then LOD was calculated and given a result of 42 ppb by using the same method (LOD = 3/k). In previous report,44 the human dose-related responses to phosgene exposure were evaluated, and the result shows that the exposure level below 25 ppm per minute couldn’t cause clinical signs and symptoms. Thus, Phos-4 test paper can be used to monitor phosgene in gas phase below the level of health risk.
Figure 7. Photograph of Phos-4 test papers upon the exposure to various amounts (0-35 ppm) of gaseous phosgene for 10 seconds under room light (upper) and 365 nm light (bottom). 800
R2 = 0.988
F@524
600
Intensity (a.u.)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Analytical Chemistry
600
400
to 50 ppm gaseous phosgene or saturated vapors of related analytes for 5 seconds, including DCP, (COCl)2, SOCl2, SO2Cl2, POCl3, HCl, DCNP. As shown in Figure 9, the test paper only exposure to phosgene atmosphere displays green fluorescence, the paper exposure to DCP vapor emits blue fluorescence and weak fluorescence for other vapors. These results show that Phos-4 test paper is selective to phosgene over relevant analytes in gas phase.
■ CONCLUSIONS In summary, the first fluorescent chemosensor, Phos-4, has been developed to discriminate between phosgene and triphosgene by dual-channel mode. The sensor Phos-4 exhibits high sensitivity (LOD = 3.2 nM for phosgene, 1.9 nM for triphosgene) and high selectivity over relevant analytes in solutions. The sensing mechanisms have been clarified, that is, because there is the difference in electrophilicity between trichloromethoxycarbonyl and chlorocarbonyl, the sensing reaction of Phos-4 to phosgene can undergo twice carbamylations to form product 1 with green fluorescence, and only once carbamylation reaction for triphosgene to form blue fluorescent product 2. To the best of our knowledge, this sensor is the first case that can discriminate phosgene and triphosgene in a dual-channel mode. Furthermore, a facile Phos-4 test paper has been fabricated by electrospinning to afford Phos-4-embedded nanofibrous membrane. The test papers exhibit a shorter response time ( 10 s) and lower LOD (42 ppb) in detection of phosgene in gas phase over those in solutions. Hence, the test paper is a promising tool for the detection of phosgene in gas phase.
200
400
0
200 0
500
600
■ ASSOCIATED CONTENT 0
10 20 30 [Phosgene] /ppm
700
Supporting Information
800
Wavelength /nm
Figure 8. Fluorescence spectra of Phos-4 test papers in the presence of different concentrations of phosgene (0-35 ppm). Inset: Calibration curve of fluorescence intensity at 524 nm as a function of phosgene concentration, λex = 420 nm.
The Supporting Information is available free of charge on the ACS Publications website. Summary of fluorescent chemosensors for phosgene, response time and stability, evidences for the sensing mechanism, details in detection of phosgene in gas phase, and copies for NMR spectra of Phos-4, compounds 1 and 3.
■ AUTHOR INFORMATION Corresponding Author *E-mail:
[email protected] Note The authors declare no competing financial interest.
■ ACKNOWLEDGMENT
Figure 9. Photograph of Phos-4 test papers upon exposure to gas/vapor of phosgene and other analytes under room light (upper) and 365 nm light (bottom). (1) blank, (2) phosgene, (3) DCP, (4) (COCl)2, (5) SOCl2, (6) SO2Cl2, (7) POCl3, (8) HCl, (9) DCNP.
Finally, to further evaluate its practical utility, the selectivity of Phos-4 test papers were investigated by exposure
This work was supported by the National Natural Science Foundation of China (Nos. 21772188, 51403195) and the Natural Science Foundation of Anhui Province (No. 1708085MB33). The authors thank Prof. Zhuan-Ling Zhang of Hefei University of Technology for her support in the electrospinning experiments.
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