Sensitivity-tunable Colorimetric Detection of Chloropicrin Vapor on

Subscriber access provided by Caltech Library

Sensitivity-tunable Colorimetric Detection of Chloropicrin Vapor on Nylon-6 Nanofibrous Membrane Based on a Detoxification Reaction with Biological Thiols Peixin Tang, Ho Ting Leung, Maria Trinidad Gomez, and Gang Sun ACS Sens., Just Accepted Manuscript • DOI: 10.1021/acssensors.8b00135 • Publication Date (Web): 28 Mar 2018 Downloaded from http://pubs.acs.org on March 28, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 25 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

ACS Sensors

1

Sensitivity-tunable Colorimetric Detection of Chloropicrin Vapor on

2

Nylon-6 Nanofibrous Membrane Based on a Detoxification Reaction with

3

Biological Thiols Peixin Tang†, Ho Ting Leung‡, Maria Trinidad Gomez‡, Gang Sun†,*

4 5

†

Division of Textiles and Clothing, University of California, Davis, CA 95616, USA

6

‡

Department of Chemistry, University of California, Davis, CA 95616, USA

7

Abstract

8

Detoxification reaction of chloropicrin in the human body with biological thiols was selected

9

for detection of chloropicrin in the air. The consumption of free sulfhydryl group in

10

biological thiols by chloropicrin is colorimetrically detectable with the addition of the

11

Ellman’s reagent. In this study, glutathione, N-acetyl-l-cysteine, l-homocysteine, cysteamine,

12

and thioglycolic acid were tested as sensing agents for chloropicrin vapor detection in ppb

13

concentration range. The reactivity of the selected biological thiols was investigated based on

14

both their redox properties and the nucleophilic strength of the sulfhydryl groups. Nylon-6

15

nanofibrous membrane and an organic solvent were used as a sensor matrix and a vapor

16

sorbent, respectively, to provide solid supports with ultrahigh surface area and enhanced

17

adsorption to chloropicrin vapor. The tunable sensitivity and detection range by using

18

different biological thiols were achieved on the sensors due to the different reactivity of thiols

19

towards chloropicrin.

20

Keywords: Detoxification reaction, fumigants, biological thiols, colorimetric sensor,

21

reactivity, Nylon-6 nanofibrous membrane

22

* Corresponding author: Tel.: +1 530 752 0840; [email protected] (G. Sun).

23

Fumigants are a group of toxic volatile chemicals that are widely used in agricultural

24

production for controlling growth of soil-borne pests.1,2 The production of strawberries,

25

potatoes, grapes and other crops is heavily dependent on the application of fumigants as

26

pre-planting pesticides in California, USA.1 Although fumigants are highly efficient in pests

27

control, the extreme toxicity of the fumigants poses a health threat to farm workers and local 1

ACS Paragon Plus Environment

ACS Sensors 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

28

residents.2 Chloropicrin is one of the fumigants that is commonly used as a replacement of

29

methyl bromide1, and is also mixed with other odorless fumigants as a warning agent. It was

30

famous as a warfare agent during World War I because of its neurotoxicity.3 The

31

over-exposure of chloropicrin could cause human serious health consequences including

32

respiratory irritation, nerve system damage, and cancer.2,3 Therefore, the US Occupational

33

Safety and Health Administration (OSHA) strictly regulates the permissible exposure limit

34

(PEL) of eight-hour exposure of chloropicrin as 100 ppb.4 Moreover, the California

35

Department of Pesticide Regulation (DPR) requires the respirator-use concentration threshold

36

of chloropicrin as 150 ppb.5 Violations of the regulations could lead to strict punishments.6

37

On the other side, easy and accurate detection of fumigants in the environment is extremely

38

important to dramatically improve protections of people from unwanted-exposure to the

39

fumigants.7

40

Traditionally, gas chromatography is used for the detection of fumigants including

41

chloropicrin in the environment.8,9 Other techniques like quartz crystal micro/nano

42

balances,10,11 laser-based photoacoustic spectroscopy,12 surface enhanced Raman scattering13

43

and electronic sensors/biosensors14,15,16 have been applied and designed for the detection of

44

different fumigants and pesticides. Although these sophisticated instruments provide precise

45

and accurate detection results with very low detection limits, the processes are time- and

46

labor-consuming and hard to be used by farm workers and residents on sites. Therefore,

47

development of sensors with the features of easy-to-use, portable and ultrasensitive is

48

indispensable. In the past decades, colorimetric sensors have attracted attentions from

49

researchers for the detections of toxic compounds like heavy metals,17,18,19 volatile organic

50

compounds,20,21 and pesticides

51

show a color change, which is visible to naked eyes after the exposure to target compounds.

52

Very high concentration of chloropicrin vapor (920‒1570 mg/m3) can be detected through a

53

colorimetric method based on quantification of nitrite ions, resulted from decomposition of

54

chloropicrin 25. Commercial chloropicrin detector tubes (SensidyneTM, FL, USA) are suitable

55

for the detection of chloropicrin in the concentration range of 0.05‒16 ppm. However, the

56

operation of the tubes relies on a gas pump for gas sampling 26. Another colorimetric sensor

22,23,24

in the environment. The desired sensor system will

2


Page 2 of 25

Page 3 of 25 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

ACS Sensors

57

system for chloropicrin has been developed based on leucomethylene blue, which can be

58

oxidized by chloropicrin to show a blue color.23 However, the sensitivity of the sensor was

59

only able to reach to 1 ppm.

60

Biological thiols like glutathione (GSH) and N-acetyl-l-cysteine (NAC) can react with

61

chloropicrin, and the reaction is fast and quantative.3 The detoxification and metabolism of

62

chloropicrin in living systems are reported as a dechlorination reaction by reacting with

63

GSH.4,27 Thus, biological thiols could be potential efficient and unique reagents for

64

chloropicrin detection.

65

According to the reaction of biological thiols and chloropicrin, we designed a novel

66

sensitivity-tunable colorimetric sensor for detection of chloropicrin vapor. The thiol reactivity,

67

more specifically the nucleophilic property, was studied and analyzed based on experimental

68

and computational results, which provided a guide to predict their detection sensitivity. The

69

optimal sensing agent was expected to present an “unambiguous” detection sensitivity to

70

naked-eyes with a detection limit which is lower than the PEL of chloropicrin. The reaction

71

rate between the thiols and chloropicrin in the liquid phase was monitored with UV-vis

72

spectrophotometer. Nylon-6 nanofibrous membrane was employed as a solid support matrix,

73

and N,N-dimethylformamide was selected as a sorbent for chloropicrin. The color changes on

74

tested sensors were measured based on RGB color system with a mobile application in a

75

smartphone.28,29

76

Materials and methods

77

Chemicals

78

Reduced glutathione (GSH), N-acetyl-l-cysteine (NAC), cysteamine (CA), monobasic

79

sodium phosphate monohydrate (MSP), sodium hydroxide, and N, N-dimethylformamide

80

(DMF) were purchased from Fischer Scientific Co. (New Jersey, USA). L-homocysteine

81

(HCYS) and thioglycolic acid (TGA) were purchased from Biosynth International Inc. (Itasca,

82

IL, USA) and TCI America (Portland, OR, USA), respectively. Chloropicrin (1000 µg/mL in

83

methanol) was bought from SPEX CertiPrepTM (New Jersey, USA). Ellman’s reagent

84

(5,5'-dithiobis-(2-nitrobenzoic acid) or DTNB) was purchased from Thermo Fisher Scientific

85

Co. (Waltham, MA, USA). Ethylenediaminetetraacetic acid disodium salt dihydrate (EDTA) 3


ACS Sensors 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

86

and formic acid were bought from Sigma-Aldrich (St. Louis, MO, USA). Nylon-6 polymer

87

pellet was purchased from ACROS Organics (New Jersey, USA). All the chemicals were used

88

as received.

89

Fabrication and SEM imaging of nylon-6 nanofibrous membrane

90

Nylon-6 nanofibrous membrane was fabricated based on a method available in a literature.30

91

Specifically, nylon-6 polymer pellets were dissolved in formic acid (15 wt%) and stirred

92

vigorously for 24 hours at room temperature. The polymer solution was then transferred into

93

four syringes capped with metallic needles. The solution was fed with a controllable rate of

94

0.15 mL/h with assistance of a syringe pump (Kent Scientific). A high voltage of 30 kV was

95

applied to four needle tips that are connected in series to generate a continuous jetting stream.

96

The resulting nylon-6 nanofibrous membranes were loaded on a grounded metallic roller

97

covered with waxed paper with a tip-to-collector distance of 15 cm. The nanofibrous

98

membrane was directly peeled out from the waxed paper and used as a sensor matrix.

99

The morphology and fiber sizes of the fabricated nylon-6 nanofibrous membrane were

100

monitored with a scanning electron microscope (SEM) (FEI/Philips XL30 FEG-SEM,

101

Oregon, USA). The membrane was attached to a carbon tape and coated with gold before

102

SEM imaging.

103

Vapor sensor setup

104

Nylon-6 nanofibrous membrane was cut into a circular shape (radius=3.0 mm). Different

105

thiols were dissolved in monobasic sodium phosphate (MSP) aqueous buffer (0.1 M MSP, 1

106

mM EDTA). The pH of the buffer was adjusted with 10 M NaOH. Each sensor was wet with

107

10 µL DMF and 7.5 µL thiol solution (1.0 mM) before putting into a 2.6 L gas chamber. Then,

108

a specific volume of chloropicrin solution was directly injected into the gas chamber with a

109

Hamilton gas-tight syringe (Reno, NV, USA). The amounts of injected chloropicrin solution

110

were calculated based on the intended molar concentration (ppm) of chloropicrin to air in the

111

gas chamber, and the results are shown Table S1. The chamber was well sealed, and the

112

sensor was exposed to different concentrations of chloropicrin for 15 min. After that, the

113

Ellman’s reagent (5,5'-dithiobis-(2-nitrobenzoic acid) or DTNB) (4 mg/mL in MSP buffer,

114

pH=8.0) was dropped onto the sensor to visually detect the residual sulfhydryl groups in the 4


Page 4 of 25

Page 5 of 25 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

ACS Sensors

115

thiols by showing different intensities of a yellow color. Chloropicrin is a highly volatile

116

toxic compound, so all the sensing procedures were run in a fume hood. The yellow color and

117

corresponding color changes shown up on the paper sensors are visible to naked eyes. The

118

deeper the color on the tested sensor stands for the lower concentration of chloropicrin vapor.

119

The color on tested sensors was monitored with a commercially available smartphone

120

application called ColorAssist (FTLapps, Inc.) to standardize the color reading process. The

121

color on the sensors was detected and reproduced into three color channels, which are red,

122

green, and blue (RGB) for intensity evaluation and chloropicrin quantification by the

123

program. RGB values ranging from 0 to 255 were measured with ColorAssist through a

124

camera on an iPhone 7 Plus (Apple Inc.). A homemade scanning box with dimensions of

125

37×32×20 cm was used to control the light condition during the color measurements. Two

126

LEDs were fixed in the box to provide a constant intensity of white light. All the sensors were

127

scanned twice to get an average number of R, G, and B values. The detection sensitivity was

128

calculated through Eq. 1. The sensor setups are shown in Scheme 1.

129

Sensitivity on sensor matrix

100%

(Eq. 1)

130

Where B0 and Bi are RGB values in the blue color channel (B value) that scanned by a

131

smartphone with ColorAssist. The RGB values are integral numbers ranging from 0 to 255.

132 133

Scheme 1. Paper-based sensor setup and detection procedures.

134

UV-vis spectroscopy

135

The sulfhydryl groups in biological thiols can break the disulfide bond in the Ellman’s

136

reagent (DTNB) and release a yellow ion (TNB2‒) in aqueous solution for the colorimetric

137

detection of the reaction. The color in the liquid system was measured on an Evolution 600 5


ACS Sensors 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

Page 6 of 25

138

UV-vis spectrophotometer (Thermo Scientific, New Jersey, USA) to obtain UV-vis

139

absorption spectra in a wavelength range of 400 nm‒500 nm. A calibration curve of different

140

concentrations of thiols is shown in supporting information in Figure S1. The residual

141

concentrations of the thiols were quantified with the assistance of DTNB through a

142

calibration method on the UV-vis spectrophotometer at λmax=412 nm.31,32 The reaction

143

sensitivity in the liquid phase was calculated according to Eq. 2.

144

Sensitivity in liquid phase

" " "

100%

(Eq. 2)

145

Where C0 and Ci are the concentrations of biological thiols in the liquid system without and

146

with the injection of chloropicrin after incubation, respectively.

147

Computational method

148

Electrostatic potentials of biological thiols and electron charges on atoms were calculated

149

based on the structure optimization that performed using Gaussian 09 program based on

150

density functional theory (DFT) with B3LYP/6-31G (d, p) basis set. The calculations were

151

performed in water system.

152

Measurement of reduction potentials

153

Reduction potentials of biological thiols under different pH conditions were measured with a

154

dual channel pH & potential meter (Accumet XL600, NJ, USA) according to a standard

155

measurement available in literature

156

diluted with an MSP buffer from stock solutions of specific thiols (5.0 mM). The final

157

concentration of each thiol solution was finally determined with a UV-vis spectrophotometer

158

following the method discussed below. The Ag/AgCl (saturated KCl) potential electrode was

159

standardized with a 200 mV±5 mV redox buffer (Aqua Solution Inc., TX, USA). The

160

standard reduction potentials of each thiol solution were read at different pH values at 25 °C,

161

and then the real reduction potentials of the thiols were calculated based on Eq. 3 33.

162

33

. Two different concentrations of thiol solutions were

E0 thiol = E0 standard + E0 Ag/AgCl

(Eq. 3)

163

Measurements and calculations of ‒SH/‒S- concentrations

164

The thiol solutions for liquid phase reaction with chloropicrin were prepared by adding 250

165

µL of 0.25 mM thiol solutions into 2.5 mL MSP buffer with specific pH. The molar ratio

166

between the thiol and chloropicrin was controlled as 2:1 with 5 µL injection of chloropicrin 6


Page 7 of 25 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

ACS Sensors

167

(1000 µg/mL).

168

The thiolate group intensity in GSH solution under different pH values were measured

169

with UV-vis spectrophotometer since the thiolate group in GSH shows an absorbance at λmax

170

= 235 nm 34. The tested solutions were prepared by adding 250 µL of 1.0 mM GSH into 2.5

171

mL MSP buffers which pH varies from 7.0 to 9.5.

172 173

The relative concentration of sulfhydryl group (‒SH) and thiolate group (‒S‒) were calculated through the Handerson-Hasselbach equation that shown in Eq (4) 35,36 [() ]

pH pKa + log [+(]

174

(Eq. 4)

175

Results and discussions

176

Detoxification reaction of chloropicrin with biological thiols

177

For the development of a sensor system which is highly sensitive to very diluted but toxic

178

concentration of chloropicrin (ppb range), selection of a detection reaction needs to meet

179

three criteria: 1) the detection reaction of chloropicrin should be ultra-sensitive and unique; 2)

180

the reaction can trigger a color change with or without additional color probes; and 3) the

181

sensing agents are non-toxic during the detection. The toxicity of chloropicrin drives a fast

182

oxidation reaction of reduced biological thiols in mammalian bodies.3 The redox reaction

183

results in an inactivation of free sulfhydryl groups (‒SH) in thiols, which can be

184

colorimetrically detected with the Ellman’s reagent. Consequently, all three requirements can

185

be achieved by using the detoxification reaction of chloropicrin with the biological thiols as a

186

detection reaction since the biological thiols are derived from the living systems.

187

The reactions of chloropicrin with glutathione (GSH), N-acetyl-l-cysteine (NAC),

188

l-homocysteine (HCYS), cysteamine (CA) and thioglycolic acid (TGA) were performed at a

189

physiological pH (pH=7.4). The inactivation amount of ‒SH groups in the biological thiols

190

and the chemical structures of the thiols are presented in Figure 1 (b) and 1 (c), respectively.

191

Clearly, the acute toxicity of chloropicrin makes the reaction with the thiols extremely fast

192

with over 50% of the thiols inactivated within 10 min, except for TGA (Figure 1b). Different

193

biological thiols in an original concentration of 0.25 mM show varied reactivity towards

194

chloropicrin. The consumption (inactivation) of ‒SH groups in CA system reached to 72%,

195

while that of ‒SH group in TGA was only 31% (Figure 1b). The reaction rate between the 7


ACS Sensors 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

Page 8 of 25

196

thiols and chloropicrin will highly affect the response time and the detection sensitivity of the

197

sensor. Therefore, the factors that potentially alter the reactivity of the thiols towards

198

chloropicrin will be discussed in detail.

199

The reported reaction mechanism of chloropicrin with biological thiols is a redox

200

reaction,4,27 so the reduction potential (RP) of the thiols may affect their reactivity towards

201

chloropicrin. As shown in Figure 1 (a), the reaction results in an oxidation of thiols (RSH) to

202

disulfides (RSSR) and a dehalogenation of chloropicrin to dichloronitromethane, which can

203

be expressed as a combination of two half-cell reactions (Scheme 2). From the equation

204

shown in Scheme 2, the smaller the RP of the anode reaction, the more spontaneous the redox

205

reaction since it leads to a more negative number of the Gibbs free energy change of the

206

whole reaction. The measured RPs of 0.25 mM thiols under physiological pH (pH=7.4) at 25

207

0

208

is expected to increase with the decreasing of RPs as NAC < GSH < TGA < HCYS < CA.

209

Unfortunately, the tested results are not fully consistent with the order of the measured RPs

210

(Figure 1b). For instance, the inactivation of ‒SH groups in TGA is much lower than that of

211

GSH, however, its RP at pH=7.4 is 223 mV lower than that of GSH. Such a fact makes us

212

believe that there might be other factors more critical in controlling the reaction rate between

213

thiols and chloropicrin.

214 215 216

C are shown in Figure 1 (b). CA has the lowest RP of ‒40 mV, and the reactivity of the thiols

Cathode: Chloropicrin + 2e + H 0 → Dichloronitromethane + Cl Anode: RSSR + 2e + 2H 0 → RSH + RSH

: 3"456789

: 3(=789

Overall: Chloropicrin + 2RSH → Dichloronitromethane + RSSR + HCl

: 3"9??

: : : 3"9?? 3"456789 − 3(=789 : ∆B −CD3"9??

217 218 219 220 221

Scheme 2. Half-cell equations of redox reaction between chloropicrin and biological thiols. : : : Where 3"456789 , 3(=789 and 3"9?? are the standard reduction potential of the reactions in cathode, anode and the whole cell, respectively. ∆B is the Gibbs free energy change of the reaction; n refers to the number of electron that transferred in the reaction; F stands for Faraday constant.

8


Page 9 of 25 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

ACS Sensors

222 223 224 225 226

Figure 1. (a) Reaction mechanism of biological thiols with chloropicrin. (b) Reaction results of biological thiols (250 µL of 0.25 mM thiols in 2.5 mL MSP buffer) with 5 µL chloropicrin (1000 µg/mL). The molar ratio is controlled as thiol:chloropicrin = 2:1) at the physiological pH (pH=7.4) with 10 min incubation time. (c) Chemical structures of biological thiols.

227

The existence of three chlorines and one nitro group on chloropicrin structure makes the

228

central carbon in chloropicrin electron deficient and electrophilic, which becomes a good

229

reaction site for nucleophiles. The ‒SH group is one of the active “soft” nucleophiles that

230

exists in the biological systems.37 As presented in Figure 1 (a), the reaction mechanism

231

between the thiols and chloropicrin can be proposed as a two-step reaction. Firstly, ‒SH

232

group in the thiols attacks the carbon in chloropicrin as a nucleophile to form an intermediate

233

which can be called as a thiol-chloropicrin (TCP) conjugate, then the second ‒SH group

234

attacks the S atom on the conjugate, which is also electron deficient, to complete the whole

235

reaction. The reaction of thiols with chloropicrin can be treated as a two-step nucleophilic

236

substitution reaction. It seems that the nucleophilicity of the ‒SH is the crucial factor for the

237

determination of the whole reaction rate. A series of tests were performed in the liquid phase

238

to evaluate the reactivity of thiols and to optimize the conditions for chloropicrin detection.

239

The generations of the disulfide bonds from the thiols reacting with chloropicrin were

240

demonstrated through

241

disulfides with the incubation of chloropicrin, shown in supporting information in Figure S2.

242

The effect of thiol dissociation

243

Since the first step of the detection reaction is a nucleophilic attack process, the

244

nucleophilicity of the ‒SH group is important for evaluating the reaction rate of the first step

13

C NMR. All the thiols can be completely or partially converted to

9


ACS Sensors 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

245

to consequently analyze the reactivity of the thiols towards chloropicrin. As we all know that

246

the negatively charged group is a better nucleophile than its neutral form, i.e. the thiolate

247

group (‒S‒) is a stronger nucleophile to attack the electrophilic chloropicrin than the neutral ‒

248

SH group in thiols.34 The effect of thiolate concentration on the reaction rate between thiols

249

and chloropicrin was first analyzed by varying the reaction pH. The results are shown in

250

Figure 2 (a). Obviously, the dissociation of ‒SH group to ‒S‒ group by increasing the pH

251

highly improved the consumption of the thiols (Figure 2a). The inactivation of ‒SH groups in

252

the thiol systems is dramatically improved by around 30% with a pH increment from 7.0 to

253

8.5. At slightly basic condition (pH=8.5), over 50% of the thiols can be inactivated by

254

chloropicrin within 5 min (Figure 2a).

255

GSH was selected as a model compound to monitor the variation of thiolate

256

concentration according to pH change, and the results are shown in Figure 2 (b). With

257

increasing the pH of GSH solution from 7.0 to 9.5, the absorbance intensity at λmax=235 nm

258

increased from 0.012 to 0.227 (Figure 1b). Therefore, it is concluded that the reaction rate

259

between the thiols and chloropicrin increased with increasing the pH since more thiolate

260

groups, a better nucleophile, were generated. The dissociation degree of ‒SH in thiols is

261

related to their pKa values of the ‒SH groups. The literature reported pKa values of the

262

selected thiols are listed in Table 1. The ‒SH group in CA is reported to have the lowest pKa

263

values (pKa=8.35) compared with other thiols, and the ‒SH group in TGA barely dissociates

264

when the pH increased from 7.0 to 8.5 since its pKa is as high as 9.93 (Table 1). Meanwhile,

265

the changes of ‒SH and ‒S‒ concentrations in percentage according to pH can be calculated

266

through Eq. 4, and the results are plotted in Figure 3. When the pH of the reaction is 7.5,

267

12.38% of ‒SH dissociates into ‒S‒ in CA, which is 5.3, 15.7, 3.0, and 206.3 times higher

268

than that of GSH (2.34%), NAC (0.79%), HCYS (4.09%), and TGA (0.06%), respectively.

269

Under this condition, the consumption of ‒SH groups in GSH, NAC, HCYS, CA, and TGA

270

by chloropicrin reaches to 50.81%, 47.24%, 59.15%, 60.24%, and 18.95%, respectively

271

(Figure 2a). With further increase in the pH, the concentrations of thiolate group in different

272

thiols keep increasing with the acceleration of thiol consumptions (Figure 3a). Based on the

273

listed pKa values and the calculated ionic concentrations, the reactivity of the thiols at a 10


Page 10 of 25

Page 11 of 25 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

ACS Sensors

274

constant pH (in a pH range of 7.0–9.0) should follow the order of CA > HCYS > GSH >

275

NAC > TGA, which agrees with the tested results (Figure 1b and Figure 2a). Consequently,

276

we proposed that the dissociation degree of ‒SH group dominates the reaction rate between

277

the thiols and chloropicrin since the nucleophilicity of the thiolate is higher than that of

278

sulfhydryl group. The nucleophilic strength difference between ‒SH and ‒S‒ groups needs

279

further evidence and analysis to support our hypothesis.

280 281 282 283 284 285 286

Figure 2. (a) Reaction results between thiols and chloropicrin according to different pH values (reaction time: 5 min). (b) Absorbance intensity of thiolate group in GSH under different pH values. The inserted graph shows the UV-vis spectrum of GSH solution with different pH values. (c) Reaction results between thiols and chloropicrin under specific pH conditions. The incubation time was 5 min. The solution preparation procedures are shown in Materials and Methods section.

287 288 289

Figure 3. Ionic concentration of (a) thiolate group (‒S‒) and (b) sulfhydryl group (‒SH) under varied pH conditions.

290

Table 1. pKa values of sulfhydryl groups in biological thiols. 11


ACS Sensors 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

Thiol-containing biomolecules Glutathione (GSH) N-acetyl-l-cysteine (NAC) l-Homocysteine (HCYS) Cysteamine (CA) Thioglycolic acid (TGA)

Page 12 of 25

pKa 9.12 9.60 8.87 8.35 9.93

Reference 38 39 40 40 39

291

The effect of electron density on functional atoms

292

The nucleophilic attack of the thiol on chloropicrin occurs in both steps of the reactions

293

(Figure 1a). Both –SH and thiolate groups are nucleophiles, their differences in nucleophilic

294

strength were further analyzed with computational calculations. The electron density of the

295

sulfur atom in different ‒SH/‒S‒ groups are calculated with Gaussian 09, and the results are

296

shown in Figure 4. The color variations from blue to red illustrate the enhancement of

297

electron density. The deeper the red color (smaller the values) on ‒SH/‒S‒ groups represents

298

the more electrons around the atom and the higher the possibility for electron donation in

299

nucleophilic attack process.41 There is no doubt that the electron density of a sulfur atom

300

dramatically increased when the ‒SH group dissociates to a thiolate group (‒S‒). The

301

negative charge on sulfur generally increased by 0.7 units when the neutral -SH group is

302

dissociated into the ‒S‒ group (Figure 4). The electron cloud around the sulfur in different

303

thiols shows an obvious color change from yellow to deep red. These results visually reveal

304

the increment of the nucleophilic strength of the thiols when the neutral compounds

305

dissociated into negatively charged thiolates, representing increased reactivity towards

306

chloropicrin if the ‒S‒groups become dominated in the reaction system (Figure 2a).

307

According to Eq. 4 and the pKa values of the thiols (Table 2), 10.0% of the thiolate

308

group can be generated in GSH, NAC, HYCS, CA, and TGA system under the pH of 8.17,

309

8.65, 7.92, 7.40, and 9.75, respectively, but the consumption rates of the thiols are still

310

different (Figure 2c). The chemical structures of the thiols could affect the electron density of

311

the sulfur atoms. As we can see from Figure 4 (c), the amino group in CA, which is an

312

electron-donation group, pushes electrons to the direction of ‒SH group, resulting in a denser

313

electron density on either ‒SH or ‒S‒ groups. However, the presence of a carboxylic group,

314

an electron-withdrawing group in TGA structure, reduces the electron density on sulfur atom

315

(Figure 4e). The electron density on ‒SH and ‒S‒ in CA is 0.076 and 0.088 units higher than 12


Page 13 of 25 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

ACS Sensors

316

that of TGA, which explains their reactivity difference, even though the concentration ratio of

317

‒SH/‒S‒ groups in these two systems are comparable. The inactivation of CA reached to

318

70.08%, nevertheless, the inactivated TGA was only 56.57% (Figure 2c). Moreover, the

319

electron density of ‒SH/‒S‒ groups in GSH, NAC, and HCYS are similar (Figure 4), which

320

resulted in a comparable inactivation of thiols (around 60.0%) when the thiolate

321

concentration was controlled at 10.0% (Figure 2c).

322

The electron density on S atoms in the thiol-chloropicrin (TCP) conjugates is another

323

factor affecting the reaction rate, especially for the rate of the first step nucleophilic

324

substitution process. The optimized TCP structures are shown in Table 2. The electronic

325

charges of S and C atoms in the TCP structures, indicated by the black arrow in the Table 2,

326

were calculated based on geometry optimizations of the TCPs. The calculated electron

327

densities on S and C atoms are listed in Table 2 as well. The sulfur atoms in the TCP

328

structures are more electron deficient and electrophilic, becoming a reaction site for the thiols.

329

Clearly, the S atoms show positive charges, whereas the C atoms in the chloropicrin fragment

330

are electron sufficient (Table 2). Theoretically, the reaction rate can be accelerated when the S

331

atom in the TCP structure is more electrophilic. Nevertheless, the results shown in Figure 2 (c)

332

demonstrate that the electron densities of S atoms are not crucial to the reaction rate. The

333

reactivity of the thiols towards chloropicrin were not significantly affected by the differences

334

of the electron density on the S atoms in TCP structures.

335

Overall, the reactivity of the thiols is controlled not only by the dissociation degree of ‒

336

SH groups, but also by the electron density on ‒SH/‒S‒ groups, which is determined by the

337

chemical structures of the thiols. The electrophilic site of the TCP affects the formation of

338

RS-SR, and this step reaction is not rate determining.

13


ACS Sensors 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

Page 14 of 25

339 340 341 342

Figure 4. Electron density of ‒SH/‒S‒ groups of different biological thiols. Table 2. Optimized chemical structures and electronic charges of C and S atoms of TCP conjugates GSH-S-CP NAC-S-CP HCYS-S-CP CA-S-CP TGA-S-CP

C S

-0.277 0.261

-0.277 0.278

-0.271 0.236

-0.251 0.223

-0.259 0.272

343

The effect of reduction potential

344

The overall reaction between chloropicrin and the biothiols is a redox reaction, so the

345

reduction potential (RP) values of the selected thiols were measured under varied pH

346

conditions and thiol concentrations. The results are shown in Figure 5. Obviously, the RP

347

values of the selected thiols present a decreasing trend with increasing pH, which is

348

consistent with the Nernst equation shown in Eq. 5. To compare the RPs of the selected thiols,

349

all the thiol solutions were kept in a same concentration so the second term in Eq. 5 is a

350

constant, which can simplify the analysis using the Nernst equation. Thus, the RP values of

351

these thiols would only be affected by pH, in a relationship of a negative slope. The measured

352

RP values of the thiols with two concentrations of 1.00 mM and 0.25 mM are shown in

353

Figure 5 (a) and 5 (b), respectively, which present an order of CA < HCYS < TGA < GSH ≈

354

NAC under a pH range of 6.5–10.5, and the order keeps the same in both thiol concentrations

355

(Figure 5). More specifically, CA possesses the highest reactivity to be oxidized by

356

chloropicrin since its lowest RP, which further decreased from ‒59 mV to ‒185 mV when the

357

pH increases from neutral to pH=10.5 at concentration of 1.00 mM (Figure 5a). Because the 14


Page 15 of 25 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

ACS Sensors

358

RPs of GSH and NAC are almost the same, the reactivity difference of these two thiols

359

should be similar due to the little difference on the nucleophilic strength of ‒SH/‒S‒ groups

360

discussed in the previous section.

36 3: −

361

:.:FGH =

J"KL JMKN

log IJ(KO JKP Q −

:.:FGH6 =

RS

Eq. (5)

362

Where Eh is the reduction potential, E0 is the standard reduction potential, n is the number of

363

electrons involved in the reaction, {A}, {B}, {C}, {D} are the concentrations of reactants and

364

products, a, b, c, and d are the stoichiometric coefficients of the reaction; h is a constant for

365

each compound.42

366

Interestingly, the measured RPs of GSH never reach to the potentials of CA over the

367

whole pH range, although the reaction result of GSH with chloropicrin at pH=8.50 is

368

comparable to that of CA with chloropicrin at pH=7.50. The consumed ‒SH groups of GSH

369

and CA were 64.07% and 60.24%, respectively (Figure 2a) when the concentration of the

370

thiols was controlled at 0.25 mM in all systems. Moreover, this phenomenon can also be

371

noticed when the concentration ratios of ‒SH/‒S‒ are comparable in NAC and HCYS systems.

372

The consumption of ‒SH/‒S‒ groups in NAC at pH=8.66 and in HCYS at pH=7.92 are 64.03%

373

and 64.39%, respectively, whereas, the RPs of NAC (268 mV) and HCYS (46 mV) differ by

374

222 mV at specific pH conditions (Figure 2c and Figure 5b). Therefore, the RP of the thiols

375

plays a less important role in determining the reaction rate between the thiols and

376

chloropicrin.

377

Thus, the nucleophilic strength of the thiol has been proven as a crucial factor for

378

accelerating the reaction rate of the thiols with chloropicrin, which provides a guidance of

379

selection of optimal thiol-containing compounds as potential sensing agents or synthesis of

380

novel sensing agents. Based on the overall analysis of the thiols, a proposed order of

381

reactivity is as following: CA > HCYS > GSH > NAC > TGA.

15


ACS Sensors 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

382 383 384 385

Figure 5. Reduction potentials of biological thiols in two different concentrations (a) 1.00 mM, and (b) 0.25 mM at 25 °C. The solution preparations are shown in Materials and Methods section.

386

Detection of chloropicrin vapor

387

Since different thiols possess versatile reactivity towards chloropicrin, they can be used as

388

different sensing agents to colorimetrically detect chloropicrin vapor with tunable

389

sensitivities and detection limits. In other words, the sensor system can be designed by

390

selecting thiols for the detection of chloropicrin in different concentration ranges. Therefore,

391

a relationship between chloropicrin concentrations versus color intensity was explored in

392

different thiol systems. The sensor setup is shown in Scheme 1, and the color intensity was

393

evaluated with the RGB color system. The RGB values of tested sensors that scanned from

394

ColorAssist are present in Figure S3. Based on our previous studies and other successful

395

sensor designs,31,43,44 the application of specifically selected organic solvents and nanofibrous

396

membranes highly improves the detection sensitivity of toxic vapor by providing the

397

ultra-high surface area and enhanced chloropicrin vapor adsorption on the surfaces. More

398

interestingly, the “paper-based” design of the sensor, which was achieved by using a

399

nanofibrous membrane, could make the sensor portable and lab-instrument free. A nylon-6

400

nanofibrous membrane (N6NM) with a fiber diameter around 200 nm made by

401

electrospinning was chosen as a sensor matrix. The SEM images of the material are shown in

402

Figure 6 (a) and 6 (b). DMF was selected as an extra sorbent based on Hansen solubility 16


Page 16 of 25

Page 17 of 25 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

ACS Sensors

403

parameter theory, due to its higher affinity to chloropicrin than that of water.30,45 The

404

application of DMF provides an enhanced attractive force to concentrate chloropicrin vapor

405

from the air to the sensor system, thereby accelerating the reaction rate and lowering the

406

detection limit. The Hansen solubility parameters of chloropicrin, water and DMF are listed

407

in Table S2. The color images and detection sensitivities of the tested sensors are shown in

408

Figure 6.

409

The chloropicrin detection results of the nanofibrous membrane sensors containing

410

different thiol systems were performed with concentration and pH of the thiol solutions

411

controlled as 1.0 mM and 8.0, and an exposure time of 15 min, and are shown in Figure 6 (c).

412

CA is not stable during the detection duration even exposing to ambient air, so CA cannot be

413

used for chloropicrin detection on the matrix. HCYS revealed the lowest detection limit of 55

414

ppb with a naked-eye distinguishable sensitivity of 35.32% (Figure 6c and 6d). The detection

415

limit in GSH, NAC and TGA systems were 110 ppb (sensitivity=36.64%), 550 ppb

416

(sensitivity = 36.94%), and 1.10 ppm (sensitivity = 33.73%), respectively, with a sensitivity

417

higher than 30%, which is defined as an “unambiguous” detection sensitivity to naked eyes.

418

The detection limits of different thiols are fully consistent with the reactivity order that

419

concluded in above discussion (HCYS > GSH > NAC > TGA). The color strip that shows

420

color intensity decrement in percentage can be found in supporting information in Figure S4.

421

Based on the versatile reactivity of the thiols with chloropicrin, the detection range of

422

chloropicrin concentration can be tuned from 2.7 ppm to 55 ppb, 3.8 ppm to 110 ppb, 2.7

423

ppm to 33 ppb, and 3.8 ppm to 275 ppb by using GSH, NAC, HCYS, and TGA as different

424

sensing agents, respectively (Figure 6c).

425

More importantly, the sensor system can be adjusted to detect threshold concentration of 5

426

chloropicrin (150 ppb)

427

HCYS and GSH. The fast response time of a sensor is essential to improve the personal

428

protection to fumigant applicators. The results of the shortest exposure time for 150 ppb

429

chloropicrin in both GSH and HCYS systems are shown in Figure 6 (e). Obviously, the

430

detection sensitivity of HCYS is much higher than that of GSH, with detection sensitivity

431

reaching to 44.24% with 5 min exposure. In GSH system, 20 min exposure achieved the

with the shortest response time by using more active thiols like

17


ACS Sensors 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

432

“unambiguous” sensitivity of 43.64% for naked-eye detection.

433

The concentration of the thiols in the sensor system can also be controlled in order to

434

adjust the detection limit and sensitivity. HCYS was used as a model compound to study the

435

effect of the thiol concentration on the detection results and limit, and the color images are

436

shown in Figure 6 (g). When decreasing the thiol concentration from 1.00 mM to 0.25 mM,

437

the color intensity on the control group decreased, which can cause the loss of sensitivity to

438

some degree. For instance, the color intensity of 0.25 mM of HCYS on the sensor was barely

439

noticeable by naked eyes, and the detection sensitivity reached to 35.80% (Figure 6h).

440

However, when the HCYS concentration is 0.50 mM, trace amounts of chloropicrin in the air

441

lead to a color change from yellow to white, which is clearly visible to naked eyes compared

442

with the pale-yellow color of the control. Consequently, 55 ppb and 33 ppb of chloropicrin

443

can be visually detected in 1.00 mM and 0.50 mM HCYS systems with a detection sensitivity

444

of 33.88% and 31.00%, respectively (Figure 6h).

445 446 447 448 449 450 451

Figure 6 (a) and (b) SEM images of the nylon-6 nanofibrous membrane. (c) Color images of tested sensors with different thiols (1.00 mM) at pH=8.0. (d) The detection sensitivity of tested sensors in (c). (e) Color images of tested sensors according to varied exposure times. The chloropicrin concentration is 150 ppb. (f) The detection sensitivity of tested sensors in (e). (g) Color images of tested sensors with different concentrations of HCYS (pH=8.0, exposure time=10 min). (h) The detection sensitivity of tested sensors in (g). 18


Page 18 of 25

Page 19 of 25 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

ACS Sensors

452

Conclusion

453

An ultra-sensitive paper-based colorimetric sensor for chloropicrin vapor has been prepared

454

based on the detoxification reaction of chloropicrin with biological thiols. The reactivity of

455

GSH, NAC, HCYS, CA, and TGA towards chloropicrin was discussed based on the reaction

456

mechanism. The reaction was found to be a two-step nucleophilic substitution process. The

457

nucleophilic strength of the thiols dominates their reactivity and detection sensitivity of

458

chloropicrin. The tunable detection limit and sensitivity were achieved in different thiol

459

systems. It was the first time that chloropicrin vapor can be detected on a paper-based

460

colorimetric sensor with a detection limit of 33 ppb and 55 ppb reading through a mobile

461

application and naked eyes, respectively. Moreover, 33 ppb of chloropicrin can also be

462

detected with naked eyes in 0.50 mM HCYS system with 10 min operation time. The shortest

463

time for 150 ppb chloropicrin detections were 20 min and 5 min in GSH and HCYS systems,

464

respectively.

465

Acknowledgement

466

This research is financially supported by California Department of Pesticide Regulations.

467 468

Supporting Information Available: The following file is available free of charge.

469

Supporting materials. Detailed information about fumigant vapor preparation, the calibration

470

curve of thiol/thiolate concentration, and reaction mechanism demonstration. Additional

471

information on the color scanning by using ColorAssist.

472

Reference

473

(1) Triky-Dotan, S.; Ajwa, H. A., Dissipation of Soil Fumigants from Soil Following

474

Repeated Applications. Pest Manag. Sci. 2014, 70, 440‒447.

475 476

(2) Gaskin, S.; Heath, L.; Pisaniello, D.; Edwards, J. W.; Logan, M.; Baxter, C., Dermal

477

Absorption of Fumigant Gases during HAZMAT Incident Exposure Scenarios-Methyl

478

Bromide, Sulfuryl Fluoride, and Chloropicrin. Toxicol. Ind. Health 2017, 33, 547‒554.

479

19


ACS Sensors 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

Page 20 of 25

480

(3) Sparks, S. E.; Quistad, G. B.; Casida, J. E., Chloropicrin: Reactions with Biological

481

Thiols and Metabolism in Mice. Chem. Res. Toxicol. 1997, 10, 1001‒1007.

482 483

(4) CA DPR (California Department of Pesticide Regulation). 2010. Evaluation of

484

Chloropicrin

485

http://www.cdpr.ca.gov/docs/emon/pubs/tac/finaleval/chloropicrin.htm

as

a

Toxic

Air

Contaminant.

486 487

(5) United State Environmental Protection Agency. Acute exposure guideline levels (AEGLs)

488

chloropicrin.

489

chloropicrin_interim_0.pdf

https://www.epa.gov/sites/production/files/2014-08/documents/

490 491

(6) Environmental Protection Magazine, $10 Million to be Paid by Defendants in Virgin

492

Islands

493

https://eponline.com/articles/2017/11/21/terminix-sentenced.aspx, 2017 (accessed Nov 21

494

2017).

Methyl

Bromide

Case.

495 496

(7)

497

http://www.nature.com/news/2010/100504/full/news.2010.218.html, 2010 (accessed May 04

498

2010). doi:10.1038/news.2010.218.

Nature,

Scientists

Fume

over

California's

Pesticide

Plans.

499 500

(8) Kanazawa, J., Determination of Chloropicrin in Fumigants by Gas-Liquid

501

Chromatography. Agr. Biol. Chem. Tokyo 1963, 27, 159‒161.

502 503

(9) Fahrenholtz, S.; Huhnerfuss, H.; Baur, X.; Budnik, L. T., Determination of Phosphine and

504

Other Fumigants in Air Samples by Thermal Desorption and 2D Heart-cutting Gas

505

Chromatography with Synchronous SIM/Scan Mass Spectrometry and Flame Photometric

506

Detection. J. Chromatogr. A 2010, 1217, 8298‒8307.

507 508

(10) Mirmohseni, A.; Houjaghan, M. R., Quartz Crystal Nanobalance in Conjunction with 20


Page 21 of 25 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

ACS Sensors

509

Principal Component Analysis for Identification and Determination of Telone, Methyl Iodide,

510

Endosulfan, and Methyl Bromide. Environ. Prog. Sustain. 2014, 33, 267‒274.

511 512

(11) Mirmohseni, A.; Rastgouy-Houjaghan, M., Application of Nanobalance Technique and

513

Principal Component Analysis for Detection of the Soil Fumigant Telone Residues in the Air.

514

J. Environ. Sci. Heal. B 2012, 47, 677‒686.

515 516

(12) Minini, K. M. S.; Bueno, S. C. E.; da Silva, M. G.; Sthel, M. S.; Vargas, H.; Angster, J.;

517

Miklos, A., Quantum Cascade Laser-based Photoacoustic Sulfuryl Fluoride Sensing. Appl.

518

Phys. B-Lasers O 2017, 123, 61.

519 520

(13) Zhu, C. H.; Wang, X. J.; Sho, X. F.; Yang, F.; Meng, G. W.; Xiong, Q. H.; Ke, Y.;

521

Wang, H.; Lu, Y. L.; Wu, N. Q., Detection of Dithiocarbamate Pesticides with a Spongelike

522

Surface-Enhanced Raman Scattering Substrate Made of Reduced Graphene Oxide-Wrapped

523

Silver Nanocubes. ACS Appl. Mater. Inter. 2017, 9, 39618‒39625.

524 525

(14) Hosseinian, A.; Vessally, E.; Babazadeh, M.; Edjlali, L.; Es’haghi, M., Adsorption

526

Properties of Chloropicrin on Pristine and Borazine-doped Nanographenes: A Theoretical

527

Study. J. Phys. Chem. Solids 2018, 115, 277‒282.

528 529

(15) Noguer, T.; Balasoiu, A. M.; Avramescu, A.; Marty, J. L., Development of a Disposable

530

Biosensor for the Detection of Metam-sodium and its Metabolite MITC. Anal. Lett. 2001, 34,

531

513‒528.

532 533

(16) El-Moghazy, A.; Soliman, E.; Ibrahim, H.; Marty, J.-L.; Istamboulie, G.; Noguer, T.,

534

Biosensor based on electrospun blended chitosan-poly (vinyl alcohol) nanofibrous

535

enzymatically sensitized membranes for pirimiphos-methyl detection in olive oil. Talanta

536

2016, 155, 258‒264.

537 538

(17) Chen, N. Y.; Zhang, Y. J.; Liu, H. Y.; Wu, X. X.; Li, Y. L.; Miao, L. J.; Shen, Z. Y.; Wu, 21


ACS Sensors 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

Page 22 of 25

539

A. G., High-Performance Colorimetric Detection of Hg2+ Based on Triangular Silver

540

Nanoprisms. ACS Sensors 2016, 1, 521‒527.

541 542

(18) Li, Y.; Wang, L. H.; Yin, X.; Ding, B.; Sun, G.; Ke, T.; Chen, J. Y.; Yu, J. Y.,

543

Colorimetric Strips for Visual Lead Ion Recognition Utilizing Polydiacetylene Embedded

544

Nanofibers. J. Mater. Chem. A 2014, 2, 18304‒18312.

545 546

(19) Li, Y.; Wang, L. H.; Wen, Y. N.; Ding, B.; Sun, G.; Ke, T.; Chen, J. Y.; Yu, J. Y.,

547

Constitution of a Visual Detection System for Lead(II) on Polydiacetylene-glycine Embedded

548

Nanofibrous Membranes. J. Mater. Chem. A 2015, 3, 9722‒9730.

549 550

(20) Li, Z.; Suslick, K. S., Portable Optoelectronic Nose for Monitoring Meat Freshness. ACS

551

Sensors 2016, 1, 1330‒1335.

552 553

(21) Wang, X. N.; Sun, X. L.; Hu, P. A.; Zhang, J.; Wang, L. F.; Feng, W.; Lei, S. B.; Yang,

554

B.;

555

Polydiacetylene/Graphene-Stacked Composite Film for Vapor-Phase Volatile Organic

556

Compounds. Adv. Funct. Mater. 2013, 23, 6044‒6050.

Cao,

W.

W.,

Colorimetric

Sensor

Based

on

Self-Assembled

557 558

(22) Sun, G.; Ghanbari, S., Colorimetric Sensor for Alkylation Agents: U.S. Patent

559

20160077070 A, 2016‒5‒17.

560 561

(23) Sun, G.; Ghanbari, S., Chloropicrin Sensor: WO Patent 2016025714 A1, 2016‒2‒18.

562 563

(24) Lee, J.; Seo, S.; Kim, J., Colorimetric Detection of Warfare Gases by Polydiacetylenes

564

Toward Equipment-Free Detection. Adv. Funct. Mater. 2012, 22, 1632‒1638.

565 566

(25) Feinsilver, L.; Oberst, F. W., Microdetermination of Chloropicrin Vapor in Air. Anal.

567

Chem. 1953, 25, 820‒821.

568

(26) Sumner, P. E.; Culpepper, A. S., Effects of Time of Day Application on Emission of 22


Page 23 of 25 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

ACS Sensors

569

Chloropicrin.

570

https://athenaeum.libs.uga.edu/bitstream/handle/10724/35234/Sumner%2077-82.pdf?sequenc

571

e=1, 2010.

572 573

(27) Zheng, W.; Yates, S. R.; Papiernik, S. K.; Guo, M. X.; Gan, J. Y., Dechlorination of

574

Chloropicrin and 1,3-dichloropropene by Hydrogen Sulfide Species: Redox and Nucleophilic

575

Substitution Reactions. J. Agr. Food Chem. 2006, 54, 2280‒2287.

576 577

(28) Dong, C.; Wang, Z. Q.; Zhang, Y. J.; Ma, X. H.; Iqbal, M. Z.; Miao, L. J.; Zhou, Z. W.;

578

Shen, Z. Y.; Wu, A. G., High-Performance Colorimetric Detection of Thiosulfate by Using

579

Silver Nanoparticles for Smartphone-Based Analysis. ACS Sensors 2017, 2, 1152‒1159.

580 581

(29) Choodum, A.; Kanatharana, P.; Wongniramaikul, W.; NicDaeid, N., A Sol-gel

582

Colorimetric Sensor for Methamphetamine Detection. Sensor Actuat. B-Chem. 2015, 215,

583

553‒560.

584 585

(30) Li, Y.; Ding, B.; Sun, G.; Ke, T.; Chen, J. Y.; Al-Deyab, S. S.; Yu, J. Y., Solid-phase

586

Pink-to-purple Chromatic Strips Utilizing Gold Probes and Nanofibrous Membranes

587

Combined System for Lead (II) Assaying. Sensor Actuat. B-Chem. 2014, 204, 673‒681.

588 589

(31) Tang, P.; Sun, G., Highly Sensitive Colorimetric Paper Sensor for Methyl Isothiocyanate

590

(MITC): Using its Toxicological Reaction. Sensor Actuat. B-Chem. 2018, 261, 178‒187.

591 592

(32) Ellman, G. L., Tissue Sulfhydryl Groups. Arch. Biochem. Biophys. 1959, 82, 70‒77.

593 594

(33) Nordstrom, D.; Wilde, F., Reduction-6.5 oxidation potential (electrode method).

595

National Field Manual for the Collection of Water-Quality Data. USGS 2005.

596 597

(34) Chasseaud, L., The Role of Glutathione and Glutathione S-transferases in the 23


ACS Sensors 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

598

Metabolism of Chemical Carcinogens and Other Electrophilic Agents. Adv. Cancer Res. 1979,

599

29, 175‒274.

600 601

(35) Po, H. N.; Senozan, N. M., The Henderson-Hasselbalch equation: Its history and

602

limitations. J Chem. Educ. 2001, 78 (11), 1499-1503.

603 604

(36) Ji, B. L.; Tang, P. X.; Yan, K.; Sun, G., Catalytic actions of alkaline salts in reactions

605

between 1,2,3,4-butanetetracarboxylic acid and cellulose: II. Esterification. Carbohyd. Polym.

606

2015, 132, 228-236.

607 608

(37) Prescher, J. A.; Bertozzi, C. R., Chemistry in Living Systems. Nat. Chem. Biol. 2005, 1,

609

13‒21.

610 611

(38) Tajc, S. G.; Tolbert, B. S.; Basavappa, R.; Miller, B. L., Direct Determination of Thiol

612

pKa by Isothermal Titration Microcalorimetry. J. Am. Chem. Soc. 2004, 126, 10508‒10509.

613 614

(39) Patel, H. M.; Williams, D. L. H., Nitrosation by Alkyl Nitrites. Part 6. Thiolate

615

Nitrosation. J. Chem. Soc., Perkin Trans. 2 1990, 37‒42.

616 617

(40) Pitman, I.; Morris, I., Covalent Additions of Glutathione, Cysteine, Homocysteine,

618

Cysteamine and Thioglycolic Acid to Quinazoline Cation. Aust. J. Che. 1979, 32, 1567‒

619

1573.

620 621

(41) Mayr, H.; Patz, M., Scales of nucleophilicity and electrophilicity: A System for Ordering

622

Polar Organic and Organometallic Reactions. Angew. Chem. Int. Edit. 1994, 33, 938‒957.

623 624

(42) Dryer, D. A.; Walczak, M. M., PH-dependent Redox Couple: Illustrating the Nernst

625

Equation Using Cyclic Voltammetry. J. Chem. Educ. 1997, 74, 1195‒1197.

626 24


Page 24 of 25

Page 25 of 25 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

ACS Sensors

627

(43) Chen, S.; Sun, G., High Sensitivity Ammonia Sensor Using a Hierarchical

628

Polyaniline/Poly(ethylene-co-glycidyl methacrylate) Nanofibrous Composite Membrane.

629

ACS Appl. Mater. Inter. 2013, 5, 6473‒6477.

630 631

(44) Schoolaert, E.; Hoogenboom, R.; De Clerck, K., Colorimetric Nanofibers as Optical

632

Sensors. Adv. Funct. Mater. 2017, 27, 1702646.

633 634

(45) C. M. Hansen, Hansen Solubility Parameters: A User's Handbook, CRC Press LLC,

635

New York, 2007.

636

TOC

637

25


Sensitivity-tunable Colorimetric Detection of Chloropicrin Vapor on

Recommend Documents