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A Single Fluorescent Chemosensor for Simultaneous Discriminative Detection of Gaseous Phosgene and a Nerve Agent Mimic Lintao Zeng, Hongyan Zeng, Lirong Jiang, Shan Wang, Ji-Ting Hou, and Juyoung Yoon Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.9b03230 • Publication Date (Web): 15 Aug 2019 Downloaded from pubs.acs.org on August 15, 2019

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Analytical Chemistry

A Single Fluorescent Chemosensor for Simultaneous Discriminative Detection of Gaseous Phosgene and a Nerve Agent Mimic Lintao Zeng,*a,b Hongyan Zeng,a Lirong Jiang,a Shan Wang,b,c Ji-Ting Hou*b,c and Juyoung Yoon*d a

Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion, Tianjin

University of Technology, Tianjin 300384, PR China. E-mail: [email protected]. (L. Zeng) b School

of Chemistry and Materials Science, Hubei Engineering University, Xiaogan 432000, PR

China. c

College of Chemistry and Chemical Engineering, Xinyang Normal University, Xinyang 464000,

PR China. E-mail: [email protected]. (J.-T. Hou) d

Department of Chemistry and Nano Science, Ewha Womans University, Seoul 03760, Korea.

E-mail: [email protected]. (J. Yoon)

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Abstract A fluorescent chemosensor has been developed for discriminative detection of phosgene and a nerve

agent

mimic

diethyl

chlorophosphate

(DCP),

which

was

comprised

of

an

anthracene-carboxyimide fluorophore and o-phenylenediamine (OPD) reaction site. Upon phosphorylation of OPD, the chemosensor displays an obvious fluorescence turn-on response towards DPC at 588 nm with instant response and a low detection limit (88 nM). By contrast, the chemosensor exhibits a colorimetric and fluorescence enhancement response at 500 nm towards phosgene with fast response (< 2 min), high selectivity, and a low detection limit (72 nM). Furthermore, chemosensor-loaded test membrane was fabricated for real-time, portable and efficient discriminative detection of trace amounts of gaseous phosgene and DCP vapor with different optical responses.

Introduction Chemical warfare agents (CWAs) are a class of highly reactive and toxic substances, such as pulmonary, nerve, and mustard agents, which are used as weapons in battlefields.1 For instance, the colorless and highly toxic phosgene (COCl2) was used in World War I that resulted in approximately 80% of deaths.2 It has been revealed that sever lung injury and respiratory damage would be induced within 20 min following exposure of humans to 20 ppm of phosgene and exposure to higher concentrations of this agent is lethal.3 Therefore, the production and use of phosgene are strictly controlled by world governments.4 Nevertheless, phosgene is widely used to prepare carbonates and carbamates in industrial production and laboratory investigations due to its two reactive acyl chloride moieties. Another class of CWAs are nerve agents, which contain phosphate or phosphite groups. The toxic effects of these substances are ascribed to irreversible bonding to the serine hydroxyl group of the enzyme acetyl cholinesterase (AChE),5-6 which leads to dysfunction of the nervous system and organ destruction. So, toxic phosgene and nerve agents are often utilized by terrorists to pose a serious and unpredictable threat to humans. For public health and safety, it is of vital importance to develop rapid, sensitive and convenient methods for detecting phosgene and nerve agents. Fluorescent chemosensors that function by chemical reactions with specific targets to produce changes in emission wavelengths and/or intensities have gained increasing attention. The broad


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utility of chemosensors is a consequence of their high selectivity and sensitivity, facile operation, and capability for use in situ and real-time detection.7-22 Not unexpectedly, a number of fluorescent chemosensors have been devised for the detection of phosgene and nerve agents. However, the majority of these chemosensors respond only to phosgene or nerve agents and not both. 23-45 So far, only one fluorescent chemosensor for discrimination between phosgene and the nerve gas mimic diethyl chlorophosphate (DCP) has been developed based on pyronin Y and o-phenyenediamine (OPD).33 Compared with those chemosensors that can be used to sense only one analyte, single ﬂuorescent chemosensors that generate different emission responses toward multiple targets are advantageous for two reasons: (1) they are more economical and (2) they avoid cross-talk that can occur when two or more fluorescent chemosensors are utilized simultaneously.46-47 Nevertheless, pyronin Y can easily undergo nucleophilic addition reaction with some nucleophilic species,48 which affects the selectivity of this sensor. Thus, it is still highly in demand to develop a specific, high sensitive and fast responsive chemosensor for simultaneous determination of DCP and phosgene with different emission. However, development of these types of chemosensors is a challenging work, because it is very difficult to find a recognition site that undergo distinguishable chemical reactions with and/or promote different emission responses to different analytes. In this work, we designed and prepared an anthracene-carboxyimide based fluorescent chemosensor PDAC for discriminative detection of phosgene and the nerve gas mimic DCP from different emission channel. This chemosensor employed anthracene-carboxyimide as reporter and o-phenyenediamine (OPD) as the reaction site for phosgene and a nerve agent mimic diethyl chlorophosphate (DCP). As shown in Scheme 1, PDAC would undergo different pathways to afford benzimidazolone-derived PDAC-Phos and phosphorylated product PDAC-DCP after reaction with phosgene and DCP, respectively. If OPD group reacts with phosgene to form benzimidazolone, the photo-induced electron transfer (PET) process would be inhibited and the fluorescence of PDAC would be lighten up. On the other hand, the electron-donating ability of OPD group would be weakened after coupling with electrophilic phosgene, which would lead to a large blue-shift in the absorption and emission spectra. By contrast, DCP reacts with OPD group to form phosphorylation, which suppresses the PET course and recover the fluorescence of PDAC. Thus, the discriminative detection of phosgene and DCP from different emission channel can be



realized by a single chemosensor. Insert Scheme 1

EXPERIMENTAL SECTION Materials and General Methods All reagents were purchased from Sigma-Aldrich, and used directly without further purifications. 1H and

13C

NMR spectra were measured on a Bruker AV spectrometer by using

tetramethylsilane (TMS) as the internal standard. High-resolution mass spectra (HRMS) were recorded on a HP-1100 LC-MS spectrometer. UV-vis absorption and fluorescence spectra were measured with a Hitachi UV-3310 spectrometer and a FL-4500 fluorometer, respectively. Relative fluorescence quantum yields were determined by using rhodamine B (Φ = 0.65 in ethanol) and fluorescein (Φ = 0.92 in 0.1 M NaOH) as references.49 Synthesis of Chemosensor PDAC Under nitrogen atmosphere, a mixture of 10-bromo-anthracene hexadecyl carboxyimide (110 mg, 0.2 mmol), 1,2-phenylenediamine (86 mg, 0.8 mmol) and NEt3 (40 mg, 0.4 mmol) in 15 ml anhydrous EtOH was stirred at 78 ℃ for 5 h. Then the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography using CH2Cl2/MeOH = 80/1 (v/v) as the eluent to afford PDAC as a dark purple solid (41 mg, 36%). 1H NMR (400 MHz, Chloroform-d) δ 10.00 (d, J = 8.8 Hz, 1H), 8.56 (d, J = 8.0 Hz, 1H), 8.09 (d, J = 10.0 Hz, 1H), 7.99 (d, J = 10.4 Hz, 1H), 7.75 (dd, J = 10.4, 6.4 Hz, 1H), 7.42 (dd, J = 8.8, 7.6 Hz, 1H), 7.33 (dd, J = 8.4, 6.8 Hz, 1H), 6.96 (d, J = 8.0 Hz, 1H), 6.92 – 6.88 (m, 1H), 6.56 – 6.47 (m, 1H), 6.35 (s, 1H), 6.21 (d, J = 9.2 Hz, 1H), 4.25 – 4.21 (m, 2H), 1.82 – 1.74 (m, 2H), 1.48 – 1.27 (m, 26H), 0.90 (t, J = 6.8 Hz, 3H). 13C NMR (100 MHz, Chloroform-d) δ/ppm 164.7, 163.7, 144.8, 137.0, 134.6, 134.4, 133.3, 131.1, 130.0, 128.9, 127.1, 125.9, 125.2, 124.2, 123.8, 123.6, 122.4, 121.8, 119.9, 118.8, 117.0, 109.8, 40.7, 32.0, 29.7, 29.5, 29.4, 28.3, 27.4, 22.7, 14.2, 13.8. HR-MS (ESI): calculated for [C38H47N3O2 + H ]+ 578.3741, found 578.3727. Preparation of solutions for spectral measurements To avoid the injury from gaseous phosgene, we used triphosgene instead of phosgene to in situ


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produce phosgene in chloroform. PDAC stock solution (10 μM) in chloroform was prepared as test solution. Stoke solutions (1 mM) of triphosgene, diethyl chlorophosphate (DCP), POCl3, SOCl2,

toluenesulfonyl

chloride

(TsCl),

diethyl

cyanophosphonate

(DECP),

dimethyl

methylphosphonate (DMMP) were prepared in chloroform. All spectroscopic experiments were carried out at room temperature. Preparation of polymeric membrane Polystyrene (3 g) and PDAC (2.5 mg) were completely dissolved in 30 mL of chloroform to form a transparent and homogeneous solution. 2 mL resultant solution was taken out and placed onto a glass plate. After naturally dried at ambient temperature, the polymeric membrane was cut into some pieces of strips. To visually determine phosgene and DCP vapors with these test strips, a predetermined amount of triphosgene/TEA (100 µM) and DCP chloroform solutions was placed in a centrifuge tube at room temperature for 5 min. Then, a test strip was put into the tube and the lid was immediately shut. After 2 min, the fluorescence color of the test strip was recorded under a 365 nm UV lamp.

Results and discussion Design and Synthesis of Chemosensor PDAC The anthracene-carboxyimide fluorophore was selected as the reporter group in PDAC because it has well documented49,50 outstanding photophysical properties including absorption and emission in the visible region, high emission quantum efficiency and a large Stokes shift. To improve the solubility and potential use in film based systems, a long alkyl chain was incorporated into anthracene-carboxyimide. An electron-donating o-phenyenediamine group was introduced to the 10-position of anthracene-carboxyimide to form intermolecular charge transfer character in PDAC and serve as the reaction site for phosgene and DCP. It was expected that DCP and phosgene would undergo different reactions with PDAC to produce benzimidazolone-derivative PDAC-Phos and phosphoramidate PDAC-DCP with different emission, respectively, as shown in Scheme 1. Moreover, the electron-donating ability of o-phenyenediamine group in PDAC would



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be weakened if OPD in PDAC react with phosgene to form benzimidazolone moiety, which would lead to blue-shift in the absorption spectra and recovery of emission from the fluorophore. In contrast, phosphorylation of OPD moiety by DCP would mainly suppress PET course, resulting in recovery of fluorescence. Thus, discrimination of phosgene and DCP can be achieved by PDAC in different emission channels. PDAC was readily prepared from 9-bromoanthracene-carboxylic acid anhydride49 in two steps, as

outlined

in

Scheme

10-bromoanthracene-carboxylic

S1 acid

(Supporting anhydride

Information). in

ethanol

1-Hexadecylamine were

refluxed

to

and form

10-bromoanthracene hexadecyl carboxyimide, which further reacted with OPD to give the target product PDAC. The chemical structures of the target and intermediates in this pathway were characterized by 1H NMR,

13C

NMR and HRMS. The detailed experimental procedure and

characterization data are provided in the Supporting Information. Optical Responses of PDAC towards Phosgene and DCP To verify the hypothesis described above, we measured the optical responses of PDAC toward phosgene and DCP in chloroform. As shown in Figure 1a, PDAC displays a strong absorption band at 520 nm, which is corresponding to the intramolecular charge transfer from amine group to anthracene-carboxyimide moiety.49 Upon addition of triphosgene to PDAC in chloroform solution containing 100 µM triethylamine (TEA, which promotes conversion of triphosgene to phosgene), the maximum absorption band at 520 nm gradually decreases and concomitantly two new absorption bands appear at 462 and 438 nm, which are the characteristic absorption bands of anthracene-carboxyimide core.49As a consequence, a noticeable colour change from red-brown to yellow was observed, which provided a visual manner to detect phosgene. The above observations indicated that intramolecular charge transfer from OPD to anthracene-carboxyimide was reduced after reaction with phosgene. Insert Figure 1

Then, we examined the fluorescence response of PDAC towards phosgene. As shown in


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Figure 1, PDAC displays a very weak fluorescence band at 500 nm in chloroform (Ф = 0.15%) due

to

photo-induced

electron

transfer

from

electron-donating

OPD

group

to

anthracene-carboxyimide. This weak emission band was greatly boosted (Ф = 12.9%) after addition of triphosgene, as shown in Figure 1b. Such tremendous emission enhancement was ascribe to the reaction that phosgene reacted with OPD to transform into a benzimidazolone moiety which inhibited the PET and ICT process. Therefore, we observed a noticeable color change and fluorescence enhancement of PDAC in the presence of phosgene. The emission intensity of PDAC at 500 nm increases as a linear function of triphosgene concentration in the range of 0-50 μM (Figure 1c), and the detection limit for phosgene was calculated to be 72 nM according to 3δ/k (Figure S1). Interestingly, the reaction between triphosgene/TEA (100 µM) and the chemosensor proceeds rapidly so that the overall sensing process is completed within 2 min (Figure 1d). These results demonstrate that the PDAC could serve as a colorimetric and fluorescence lighting-up chemosensor for rapid, sensitive, and visual detection of phosgene. Furthermore, the fluorescence response of PDAC to triphosgene in the absence of TEA (100 µM) was determined in order to certify that its reaction with phosgene contributes to the observed absorption and fluorescence spectral changes. As shown in Figure S2, PDAC (10 µM) exhibits a negligible fluorescence change after addition of triphosgene for 10 min, while an approx. 1-fold emission enhancement at 500 nm was observed in the following 10 min, which could be ascribed to the slow release of phosgene originated from the dissociation of triphosgene. Compared with the large fluorescence enhancement of PDAC promoted by addition of triphosgene and TEA (100 µM), we conclude that the chemosensor PDAC is responsive to phosgene not triphosgene. Insert Figure 2

Next, we assessed the optical responses of PDAC to the nerve agent mimic DCP, as shown in Figure 2. Upon the addition of DCP, PDAC displays a hypochromic shift from 520 nm to 474 nm in the absorption band, which is much less than that caused by phosgene. Besides, the addition of DCP results in a large emission enhancement of PDAC at 588 nm with a fluorescence quantum yield of 3.2% (Figure 2b). It should be noted that the changes in emission and absorption spectra



of PDAC triggered by phosgene are distinguishable from those promoted by DCP, which fulfills the requirements of chemosensor for discriminative detection of these two species. A linear relationship exists between the ﬂuorescence intensity and DCP concentration in the range of 0–100 μM (Figure 2c) with a detection limit of 88 nM (Figure S3). Moreover, PDAC can sense DCP in several seconds, which is much shorter than that initiated by triphosgene/TEA (100 µM) (Figure 2d). Hence, PDAC can be used to discriminatively determine DCP and phosgene according to different colour, emission and response time. Sensing Mechanism of Chemosensor PDAC To gain some information about the sensing mechanism, we investigated the reaction between phosgene and PDAC, which is proposed to be responsible for the observed optical changes described above. For this purpose, we carried out an experiment that triphosgene/TEA (100 µM) reacted with PDAC for 10 min and the major green fluorescence product was separated for 1H NMR and MS measurement. As depicted in Figure 3 and Figure S5, the chemical shift at 6.31 ppm was assigned to NH (H12), which completely disappeared after reaction with phosgene. Besides, the aromatic proton signals of OPD group were shifted to downfield, suggesting that the OPD group in PDAC had been transformed into less electron-donating benzimidazolone after reaction with phosgene. HR-MS (shown in Figure S6) also confirmed the chemical structure of PDAC-Phos, where the peak at m/z 604.3514 is corresponding to PDAC-Phos. From these observations, it can be concluded that −NH and NH2 in OPD group couples with electrophilic phosgene to from a benzimidazolone. Consequently, the electron-donating ability of –NH group in PDAC was declined and the PET course was prohibited, which resulted in a significant blue-shift in the UV−vis absorption spectra and a great fluorescence enhancement of PDAC. We also made an effort to isolate the product from the reaction of PDAC with DCP. Unfortunately, we did not obtain pure PDAC-DCP because the product has high polarity and is unstable on silica gel column. So, the crude reaction mixture was subjected to HR-MS analysis. Figure S7 shows the HR-MS spectrum of crude mixture, where a peak appears at m/z 714.4025, which is corresponding to PDAC-DCP (calculated m/z of [PDAC-DCP + H]+ is 714.4030). Insert Figure 3


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Considering that two amine groups of OPD in PDAC could be phosphorylated, a control compound 2 with picolyamine moiety at 10-position of the fluorophore was prepared and its optical responses toward triphosgene and DCP were examined. As shown in Figure 4, compound 2 displayed obvious absorption and emission at 530 nm and 610 nm, respectively, while the addition of triphosgene induced no changes on its optical spectra in 2 min, indicating the specific reactivity of OPD toward phosgene. However, both the absorbance and emission of compound 2 declined after addition of DCP, which suggested that the phosphorylation of amine at 10-position of the fluorophore would partially quench its fluorescence. Accordingly, the optical response of compound 2 toward DCP was obviously different from that of PDAC toward DCP. Therefore, the phosphorylation of PDAC by DCP was speculated to occur at the bare amine of OPD group and prevent the secondary phosphorylation of the other one due to strong steric hindrance. Thus, chemosensor PDAC showed an emission enhancement toward DCP. Insert Figure 4

Selectivity of Chemosensor PDAC towards Phosgene and DCP To demonstrate the target specificity of PDAC, we determined its fluorescence response to other analytes. Figure 5 shows that only phosgene induces a large increase in the intensity of emission at 500 nm (excitation 440 nm) and that only DCP causes an emission increase of the PDAC at 588 nm (excitation 500 nm) among the tested substances, including POCl3, SOCl2, toluenesulfonyl chloride (TsCl), diethyl cyanophosphonate (DECP), dimethyl methylphosphonate (DMMP), triphosgene/TEA (100 µM) and DCP. It should be noted that the addition of the nerve agent mimics DECP and DMMP to solutions of PDAC did not bring about an emission response. We reasoned that DCP contains a highly reactive chlorophosphate group, which can react with amine group of this chemosensor to cause a remarkable fluorescence enhancement. By contrast, DECP and DMMP have no such reactive groups and cannot react with PDAC. Hence, the chemosensor can discriminate DCP from DECP and DMMP. These observations indicate that



PDAC has good selectivity to phosgene and DCP over other nerve-gas mimics and acryl chlorides. Especially, to elucidate the fluorescence response of the chemosensor toward the coexistence of DCP and phosgene, we checked the emission changes of PDAC in the presence of both agents. As shown in Figure S4, the chemosensor displayed very weak fluorescence at 500 nm in the presence of DCP (100µM). Whereas, the fluorescence at 500 nm was greatly promoted after the addition of phosgene (45 µM), implying that DCP did not interfere with the determination of phosgene. Similarly, tremendous fluorescence enhancement of the chemosensor at 588 nm triggered by DCP (100 µM) was observed in the presence of phosgene (45 µM). Therefore, our chemosensor can discriminatively determine DCP and phosgene from different emission channel even when they coexist. Insert Figure 5

Analyte detection using a chemosensor PDAC-loaded film Inspired by the desirable optical properties, we would like to exploit the practical applications of PDAC for detection of phosgene and DCP. PDAC was firstly immobilized into the polystyrene (0.083%, w/w) to obtain the PDAC-loaded polymeric film with an amaranthine color and dim fluorescence. Upon exposure to increasing amount of phosgene vapor (0 - 40 ppm) at room temperature for 2 min, the color of the film gradually changed from amaranthine to fawn (Figure S8a), and the fluorescence color under a UV lamp (365 nm) became green (Figure 6a), which could be readily observed by naked eyes. It is worth noting that the PDAC-loaded film can give an obvious color change and fluorescence color even when phosgene vapor is at a concentration as low as 1 ppm. It has been mentioned that exposure to 20 ppm phosgene for 20 min leads to sever lung injuries and respiratory damage for humans. Therefore, PDAC-loaded polymeric film can fully meet the requirements for phosgene detection within safety margin. In contrast, exposure of the film to DCP vapor (0 - 40 ppm) triggered a color change from amaranthine to brown (Figure S8b), along with a fluorescence color change to cantaloupe (Figure 6b). The


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fluorescence changes can be facilely distinguished at a concentration of DCP vapor even lower than 5 ppm. Insert Figure 6

Eventually, the selectivity of the film to phosgene and DCP was investigated. As displayed in Figure 7, the color changes of the film and its bright fluorescence emission under UV lamp (365 nm) could be visualized in the presence of phosgene and DCP, and the optical changes initiated by phosgene and DCP were visually discriminating. In contrast, the other tested species induced negligible changes of the film. These observations verify that PDAC-loaded polymeric film shows a great potential in the practical discriminatory detection of trace amounts of phosgene and DCP. Insert Figure 7

Conclusion In summary, we developed an OPD-anchored anthracene carboxyimide-based fluorescent chemosensor PDAC for discriminatory sensing of phosgene and a nerve agent mimic DCP. Owing to the different reactions, the chemosensor displays an obvious fluorescence turn-on response towards DPC at 588 nm with instant response and a low detection limit (88 nM). By contrast, the chemosensor exhibits a colorimetric and fluorescence enhancement response at 500 nm towards phosgene with fast response (< 2 min), high selectivity, and a low detection limit (72 nM). Finally, a chemosensor PDAC-loaded polymeric film was fabricated and demonstrated to have practical utility in the detection of phosgene and DCP vapours. This investigation not only develop a simple yet efficient method for the rapid and sensitive detection of CWAs, but also highlights a strategy for designing single fluorescent chemosensor for two analytes.

Conflicts of interest All authors of this manuscript declare no research conflicts.



Acknowledgements J.-T.H. and L.Z. acknowledge grants from the Hubei Provincial Natural Science Foundation (2018CFB264), the Major Program of Technical Innovation of Hubei Province (2018ACA152) and the National Natural Science Foundation of China (nos. 21203138, 21807029); S.W. acknowledges grants from the Hubei Provincial department of Education Science and Technology Research Projects (No. Q20182704); J.Y. thanks the National Research Foundation of Korea (NRF), which was funded by the Korean government (MSIP) (No. 2012R1A3A2048814).

Supporting Information Synthesis and characterization data of PDAC and compound 2, determination of the detection limit, simultaneous discriminative determination of coexisting phosgene and DCP, and the investigation of the sensing mechanism.

Notes and references (1) Evison, D.; Hinsley, D.; Rice, P. Chemical weapons. Clin. Rev. 2002, 324, 332−335. (2) Prentiss, A. M. Chemicals in War, 1st ed.; McGraw-Hill: New York, 1937, 216−217. (3) Plahovinsak, J.; Perry, M.; Knostman, K.; Segal, R.; Babin, M. Characterization of a nose-only inhaled phosgene acute lung injury mouse model. Inhalation Toxicol. 2015, 27, 832−840. (4) Watson, A.; Opresko, D.; Young, R. A.; Hauschild, V.; King, J. K. Bakshi in Handbook of Toxicology of Chemical Warfare Agents, 2nd ed. (Ed.: R. C. Gupta), Academic Press, Boston, 2015, 87−109. (5) Marrs, T. Organophosphate poisoning. Pharmacol. Ther. 1993, 58, 51. (6) Szinicz, L.; Worek, F.; Thiermann, H.; Kehe, K.; Eckert, S.; Eyer, P. Development of antidotes: Problems and strategies. Toxicology. 2007, 233, 23−30. (7) Duan, C.; Won, M.; Verwilst, P.; Xu, J.; Kim, H. S.; Zeng, L.; Kim, J. S. In vivo imaging of endogenously produced HClO in zebrafish and mice using a bright, photostable ratiometric fluorescent probe. Anal. Chem. 2019, 91, 4172−4178. (8) Cao, X.; Ding, Q.; Li, Y.; Gao, A.; Chang, X. Continuous multi-channel sensing of volatile


Page 12 of 21

Page 13 of 21 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


acid and organic amine gases using a fluorescent self-assembly system. J. Mater. Chem. C. 2019, 7, 133−142. (9) Hou, J. T.; Kim, H. S.; Duan, C.; Ji, M. S.; Wang, S.; Zeng, L.; Ren, W. X.; Kim, J. S. A ratiometric fluorescent probe for detecting hypochlorite in the endoplasmic reticulum. Chem. Commun. 2019, 55, 2533−2536. (10) Wang, X.; Li, P.; Ding, Q.; Wu, C.; Zhang, W.; Tang, B. Observation of acetylcholinesterase in stress-induced depression phenotypes by two-photon fluorescence imaging in the mouse brain. J. Am. Chem. Soc. 2019, 141, 2061−2068. (11) Yang, X. P.; Liu, W.; Tang, J.; Li, P.; Weng, H.; Ye, Y.; Xian, M.; Tang, B.; Zhao, Y. A multi-signal mitochondria-targeted fluorescent probe for real-time visualization of cysteine metabolism in living cells and animals. Chem. Commun. 2018, 54, 11387−11390. (12) Hou, J. T.; Ren, W. X.; Li, K.; Seo, J.; Sharma, A.; Yu, X. Q.; Kim, J. S. Fluorescent bioimaging of pH: from design to applications. Chem. Soc. Rev. 2017, 46, 2076−2090. (13) Duan, C.; Zhang, J. F.; Hu, Y.; Zeng, L.; Su, D.; Bao, G. M. A distinctive near-infrared fluorescence turn-on probe for rapid, sensitive and chromogenic detection of sulfite in food. Dyes Pigm. 2019, 162, 459-465. (14) Wu, D.; Sedgwick, A. C.; Gunnlaugsson, T.; Akkaya, E. U.; Yoon, J.; James, T. D. Fluorescent chemosensors: the past, present and future. Chem. Soc. Rev. 2017, 46, 7105−7123. (15) Mei, J.; Leung, N. L. C.; Kwok, R. K. T.; Lam, J. W. Y.; Tang, B. Z. Aggregation-induced emission: together we shine, united we soar!. Chem. Rev. 2015, 115, 11718−11940. (16) Wu, X.; Zhu, W. Stability enhancement of fluorophores for lighting up practical application in bioimaging. Chem. Soc. Rev. 2015, 44, 4179−4184. (17) Yuan, L.; Lin, W.; Zheng, K.; He, L.; Huang, W. Far-red to near infrared analyte-responsive fluorescent probes based on organic fluorophore platforms for fluorescence imaging. Chem. Soc. Rev. 2013, 42, 622−661. (18) Yan, J.; Lee, S.; Zhang, A.; Yoon, J. Self-immolative colorimetric, fluorescent and chemiluminescent chemosensors. Chem. Soc. Rev. 2018, 47, 6900-6916. (19) Fu, W.; Yan, C.; Guo, Z,; Zhang, J. J.; Tian, H.; Zhu, W. H. Rational design of near-infrared aggregation-induced-emission-active probes: in situ mapping of amyloid-β plaques with



ultrasensitivity and high-fidelity. J. Am. Chem. Soc. 2019, 141, 3171-3177. (20) Wang, S.; Gu, K.; Guo, Z.; Yan, C.; Yang, T.; Chen, Z.; Tian, H.; Zhu, W. H. Self-assembly of a monochromophore-based polymer enables unprecedented ratiometric tracing of hypoxia. Adv. Mater. 2019, 31, 1805735. (21) Zhang, J.; Wang, Q.; Guo, Z.; Zhang, S.; Yan, C.; Tian, H.; Zhu, W. H. High-fidelity trapping of spatial-temporal mitochondria with rational design of aggregation-induced emission probes. Adv. Funct. Mater. 2019, 29, 1808153. (22) Hu, Q.; Qin, C.; Huang, L.; Wang, H.; Liu, Q.; Zeng, L. Selective visualization of hypochlorite and its fluctuation in cancer cells by a mitochondria-targeting ratiometric fluorescent probe. Dyes Pigm. 2018, 149, 253-260. (23) Chen, L.; Wu, D.; Yoon, J. Recent advances in the development of chromophore-based chemosensors for nerve agents and phosgene. ACS Sens. 2018, 3, 27−43. (24) Kim, K.; Tsay, O. G.; Atwood, D. A.; Churchill, D. G. Destruction and detection of chemical warfare agents. Chem. Rev. 2011, 111, 5345–5403. (25) Burnworth, M.; Rowan, S. J.; Weder, C. Fluorescent sensors for the detection of chemical warfare agents. Chem.-Eur. J. 2007, 13, 7828−7836. (26) Eubanks, L. M.; Dickerson, T. J.; Janda, K. D. Technological advancements for the detection of and protection against biological and chemical warfare agents. Chem. Soc. Rev. 2007, 36, 458–470. (27) Hu, Q.; Duan, C.; Wu, J.; Su, D.; Zeng, L.; Sheng, R. Colorimetric and ratiometric chemosensor for visual detection of gaseous phosgene based on anthracene carboxyimide membrane. Anal. Chem. 2018, 90, 8686−8691. (28) Zhang, Y.; Peng, A.; Jie, X.; Lv, Y.; Wang, X.; Tian, Z. A BODIPY-based fluorescent probe for detection of subnanomolar phosgene with rapid response and high selectivity. ACS Appl. Mater. Interfaces 2017, 9, 13920−13927. (29) Chen, L.; Wu, D.; Kim, J. M.; Yoon, J. An ESIPT-based fluorescence probe for colorimetric, ratiometric, and selective detection of phosgene in solutions and the gas phase. Anal. Chem. 2017, 89, 12596−12601. (30) Xia, H. C.; Xu, X. H.; Song, Q. H. A fluorescent chemosensor for selective detection of phosgene in solutions and in gas phase. ACS Sens. 2017, 2, 178−182.


Page 14 of 21

Page 15 of 21 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


(31) Wang, S. L.; Zhong, L.; Song, Q. H. A ratiometric fluorescent chemosensor for selective and visual detection of phosgene in solutions and in the gas phase. Chem. Commun. 2017, 53, 1530-1533. (32) Xie, H.; Wu, Y.; Zeng, F.; Chen, J.; Wu, S. An AIE-based fluorescent test strip for the portable detection of gaseous phosgene. Chem. Commun. 2017, 53, 9813−9816. (33) Zhou, X.; Zeng, Y.; Chen, L.; Wu, X.; Yoon, J. A fluorescent sensor for dual-channel discrimination between phosgene and a nerve-gas mimic. Angew. Chem. 2016, 128, 4807–4811. (34) Xia, H. C.; Xu, X. H.; Song, Q. H. BODIPY-based fluorescent sensor for the recognization of phosgene in solutions and in gas phase. Anal. Chem. 2017, 89, 4192–4197. (35) Hu, Y.; Chen, L.; Jung, H.; Zeng, Y.; Lee, S.; Swamy, K. M. K.; Zhou, X.; Kim, M. H.; Yoon, J. Effective strategy for colorimetric and fluorescence sensing of phosgene based on small organic dyes and nanofiber platforms. ACS Appl. Mater. Interfaces 2016, 8, 22246−22252. (36) Liu, X.; Gong, Y.; Zheng, Y.; Xiong, W.; Wang, C.; Wang, T.; Che,Y.; Zhao, J. Sensitive detection of a nerve-agent simulant through retightening internanofiber binding for fluorescence enhancement. Anal. Chem. 2018, 90, 1498−1501. (37) Sun, X.; Dahlhauser, S. D.; Anslyn, E. V. New autoinductive cascade for the optical sensing of fluoride: application in the detection of phosphoryl fluoride nerve agents. J. Am. Chem. Soc. 2017, 139, 4635−4638. (38) Kim, Y.; Jang, Y. J.; Lee, D.; Kim, B. S.; Churchill, D. G. Real nerve agent study assessing pyridyl reactivity: Selective fluorogenic and colorimetric detection of Soman and simulant. Sens. Actuators, B 2017, 238, 145−149. (39) Kumar, V.; Rana, H. Chromogenic and fluorogenic detection and discrimination of nerve agents Tabun and Vx. Chem. Commun. 2015, 51, 16490−16493. (40) Lei, Z.; Yang, Y. A concise colorimetric and fluorimetric probe for sarin related threats designed via the “covalent-assembly” approach. J. Am. Chem. Soc. 2014, 136, 6594−6597. (41) Dale, T. J.; Rebek, J. Hydroxy oximes as organophosphorus nerve agent sensors. Angew. Chem. Int. Ed. 2009, 48, 7850−7852. (42) Zhang, S. W.; Swager, T. M. Fluorescent detection of chemical warfare agents: functional



group specific ratiometric chemosensors. J. Am. Chem. Soc. 2003, 125, 3420−3421. (43) Kim, Y.; Jang, Y. J.; Mulay, S. V.; Nguyen T. T. T.; Churchill, D. G. Fluorescent sensing of a nerve agent simulant with dual emission over wide pH range in aqueous solution. Chem. Eur. J. 2017, 23, 7785-7790. (44) Barba-Bon, A.; Costero, A. M.; Gil, S.; Sancenónacd, F.; Martínez-Máňez, R. Chromo-fluorogenic BODIPY-complexes for selective detection of V-type nerve agent surrogates. Chem. Commun. 2014, 50, 13289-13291. (45) Kim, T.; Maity, S. B.; Bouffard, J.; Kim, Y. Molecular rotors for the detection of chemical warfare agent simulants. Anal. Chem. 2016, 88, 9259−9263. (46) Ren, M.; Deng, B.; Zhou, K.; Kong, X.; Wang, J. Y.; Lin, W. Single fluorescent probe for dual-imaging viscosity and H2O2 in mitochondria with different fluorescence signals in living cells. Anal. Chem. 2017, 89, 552−555. (47) Chen, W.; Pacheco, A.; Takano, Y.; Day, J. J.; Hanaoka, K.; Xian, M. A single fluorescent probe to visualize hydrogen sulfide and hydrogen polysulfides with different fluorescence signals. Angew. Chem. Int. Ed. 2016, 55, 9993–9996. (48) Sun, Y.-Q.; Liu, J.; Zhang, H.; Huo, Y.; Lv, X.; Shi, Y.; Guo, W. A Mitochondria-Targetable Fluorescent Probe for Dual-Channel NO Imaging Assisted by Intracellular Cysteine and Glutathione. J. Am. Chem. Soc. 2014, 136, 12520−12523. (49) Xu, J.; Niu, G.; Wei, X.; Lan, M.; Zeng, L.; Kinsella, J. M.; Sheng, R. A family of multi-color anthracene carboxyimides: Synthesis, spectroscopic properties, solvatochromic fluorescence and bio-imaging application. Dyes Pigm. 2017, 139, 166−173. (50) Hou, X.; Peng, J.; Zeng, F.; Yu, C.; Wu, S. An anthracenecarboximide fluorescent probe for in vitro and in vivo ratiometric imaging of endogenous alpha-L-fucosidase for hepatocellular carcinoma diagnosis. Mater. Chem. Front. 2017, 1, 660−667.


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Figures and Captions

O

N

O

N HN

PDAC-Phos

O

O Cl

O

C14H29

C14H29

C14H29

N

Cl

Phosgene

HN

O

O

N

O

OEt EtO P Cl O

DCP

H 2N PDAC

HN OEt EtO P HN O PDAC-DCP

Scheme 1 Design strategy of PDAC for discrimination between phosgene and DCP.

Figure 1. (a) UV-vis absorption and (b) fluorescence titration of PDAC (10 µM) upon gradual addition of triphosgene (0 – 9 equiv) in chloroform. Inset: colorimetric and fluorescence changes of PDAC towards phosgene under daylight or a UV lamp (365 nm). (c) Linear relationships of fluorescence intensity (F500) for PDAC (10 μM) versus concentrations of triphosgene/TEA (100 µM). (d) Time-dependent fluorescence response of PDAC (10 μM) to triphosgene (90 μM)/TEA (100 µM) in chloroform. λex = 440 nm, slits: 2.5 nm/5 nm. Each spectrum was recorded after 2 min.



Figure 2. (a) UV-vis absorption and (b) fluorescence titration of PDAC (10 µM) with DCP (0 – 20 equiv) in chloroform. (c) Linear relationships of fluorescence intensity (F588) for PDAC (10 μM) versus concentrations of DCP. (d) Time-dependent fluorescence response of PDAC (10 μM) to DCP (200 µM) in chloroform. Inset: colorimetric and fluorescence changes of PDAC towards DCP under daylight or a UV lamp (365 nm). λex = 500 nm, slits: 5 nm/5 nm. Each spectrum was recorded after 1 min.

Figure 3. Partial 1H NMR spectra of PDAC and PDAC-Phos (CDCl3, 400 MHz).


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Figure 4. (a) UV-vis absorption and (b) fluorescence spectra of compound 2 (10 μM) in the presence of triphosgene/TEA (90 µM) and DCP (200 µM) in CHCl3. λex = 524 nm, slits: 5 nm/5 nm.

Figure 5. (a) Fluorescence spectra and (b) emission intensity changes at 500 nm of PDAC (10 µM) after addition of triphosgene (9 equiv)/TEA (100 μM) and other analytes (90 μM). λex = 440 nm, slits: 2.5 nm/5 nm. (c) Fluorescence spectra and (d) emission intensity changes at 588 nm of PDAC (10 µM) after addition of DCP (20 equiv) and other analytes (200 μM). λex = 500 nm, slits: 5 nm/5 nm.



Figure 6. Photograph of fluorescence changes of PDAC-based polystyrene film upon exposure to various amounts of (a) phosgene and (b) DCP vapor (0 – 40 ppm), respectively.

Figure 7. Photograph of (a) color and (b) fluorescence response of PDAC-based polystyrene membrane upon exposure to 40 ppm of gaseous phosgene, DCP vapor and various analytes. (1) Blank, (2) POCl3, (3) SOCl2, (4) TsCl, (5) DECP, (6) DMMP, (7) Triphosgene/TEA (100 µM), (8) DCP.


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