Colorimetric Detection of Carcinogenic Alkylating Fumigants on Nylon

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Colorimetric Detection of Carcinogenic Alkylating Fumigants on Nylon-6 Nanofibrous Membrane. Part I: Investigation of 4-(p-Nitrobenzyl) Pyridine as A “New” Sensing Agent with Ultra-High Sensitivity Peixin Tang, Gang Sun, and Ho Ting Leung Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.8b04775 • Publication Date (Web): 23 Nov 2018 Downloaded from http://pubs.acs.org on November 24, 2018

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Analytical Chemistry

1

Colorimetric Detection of Carcinogenic Alkylating Fumigants on Nylon-6

2

Nanofibrous Membrane. Part I: Investigation of 4-(p-Nitrobenzyl) Pyridine

3

as A “New” Sensing Agent with Ultra-High Sensitivity Peixin Tang†, Ho Ting Leung‡, Gang Sun† *

4 5 6 7

†Division

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

‡Department

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

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

1

ACS Paragon Plus Environment

Analytical Chemistry 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

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ABSTRACT

9

Alkylating fumigants are widely used in agricultural production for the control of soil-borne

10

pests, but the acute toxicity and carcinogenicity of these chemicals pose a health threat to farm

11

workers as well as residents. A nanofibrous membrane-based colorimetric sensor relying on

12

the nucleophilic substitution reaction of 4-(p-nitrobenzyl) pyridine (NBP) is introduced for the

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convenient and portable detection of alkylating fumigants. Comparing with the traditional use

14

of NBP in detecting alkylating agents, this sensor system achieves a ppb-level detection

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sensitivity toward alkylating fumigant gases without a high-temperature incubation or the

16

addition of extra bases. The mechanisms of the detection reaction and the detection sensitivities

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of different fumigants were studied with computational methods, and the results

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comprehensively prove the proposed optimized detection mechanisms. The detection limit of

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methyl iodide, methyl bromide, and 1, 3-dichloropropene successfully reaches to the limiting

20

exposure concentrations (PEL or REL) with a naked-eye detectable color difference within 5

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min with a dynamic detection procedure. The designed sensing system is promising for a real-

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time monitoring of the air quality related to alkylating fumigants in the environment, especially

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in agricultural and industrial areas.

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Keywords: Colorimetric sensor, NBP, Alkylating agent, Air quality monitoring, Nanomaterial.

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Alkylating agents are widely used not only in organic synthesis but also in agricultural

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applications. Alkylating fumigants such as methyl bromide (MeBr) and methyl iodide (MeI)

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were applied as effective fumigants in the production of strawberries, grapes, carrots and other

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major crops. Based on the environmental issues, various synthetic and bio-based compounds

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are developed as a pre-plant pesticide to replace MeBr.1,2 1, 3-Dichloropropene (1, 3-D) is one

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of the synthetic fumigants that is widely used nowadays, and its application amount is

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continuously increasing.3 However, the acute toxicity of these alkylating fumigants poses a

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health threat to the farm workers and the residents. The high vapor pressure of the alkylating

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fumigants makes them easily diffuse from the soil to the atmosphere.1,3 Even worse, most of

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the alkylating agents are odorless and colorless, making them difficult to be noticed before

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causing any adverse effect. Alkylating fumigants are highly reactive with nucleophiles like

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proteins and DNA in the human body to disorder the physiological functions. The overexposure 2


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of the alkylating fumigants will lead to ensuing abnormal cell deaths and DNA sequence

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defects, which are manifested as the mutagenic and carcinogenic effects.4,5

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Traditionally, the detection of fumigants in the environment is performed with

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sophisticated laboratory-instruments like GC-MS.6‒8 Unfortunately, the high cost of the

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instruments, the complex and long-term sample preparation, and the requirement of

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experienced operators highly limit their applications for real-time monitoring and on-site tests.

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Therefore, the development of a sensor with the features of being easy-to-use, portable, and

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ultrasensitive is urgent for improving personal protections. The study of a novel and easy

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detection method for agricultural toxicants basically relies on three approaches. First, the mass

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change on a specific detector is monitored for alkylators detection;9 another method is based

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on the generation of electric signals of the sensor when the active sites physically or covalently

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interact with the target compounds;10‒12 lastly, the detection of alkylators can be achieved

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through optical signals either with newly synthesized compounds13‒17 or chemically modified

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materials.18‒21

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Among them, the optical signals have also been widely applied in detecting various

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compounds in the environment22‒24 and physiological systems25,26 due to the legibility of the

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detection. In recent decades, the sensors are started to be embedded into paper-based and

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nanosized materials to make the devices portable and highly sensitive by providing an ultra-

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high surface area for the detection.27‒29 Polydiacetylene is one of the most popular colorimetric

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sensing agents that is modified into liposomes for pesticide and warfare agent detection in both

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liquid and vapor phases with a sub-ppm detection limit.30 New colorimetric or fluorescence

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sensing agents based on chemical reactions, metal ion aggregation or dispersion and polymer

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interactions are synthesized for the detection of alkylating pesticides, nerve agents and other

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toxic compounds.17,31 However, most of the synthesized probes still have restrictions for

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practical uses.

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4-(p-Nitrobenzyl) pyridine (NBP) was first developed as a colorimetric probe to monitor

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the alkylating reactions based on the toxicology of alkylators in the human body.32 The reactive

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site in NBP was found to have the similar nucleophilicity as that of guanine, which was reported

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as the most reactive cite in DNA with alkylating toxicants.33 However, the generation of a color

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signal depends on a long-term heating and the presence of extra bases in the traditional 3



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methods.33 NBP derivative was synthesized to eliminate the base addition and stabilize the

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color signal during the detection, but the detection limit and response time of high

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concentration of MeI is not satisfied with the safety requirement.14 NBP-structure can also be

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found in other sensor designs. Zhao, L., and coworkers reported a strategy to colorimetrically

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detect Cr (III) in wastewater by modified NBP-structures onto gold nanoparticles.34

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Unfortunately, there are rare colorimetric sensors for widely used but highly toxic agricultural

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fumigants.14,35,36

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In this study, we report a design of ultrasensitive, nanofibrous membrane-based, and

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naked-eye detectable colorimetric sensor for alkylating fumigants based on their nucleophilic

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substitution reactions with NBP. The application of a concentrated NBP in our sensor system

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is proposed to eliminate the addition of an external base and the necessity of a high-temperature

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incubation during the detection. The proposed detection mechanism is proved with Gaussian

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calculations. Moreover, nylon-6 nanofibrous membrane is fabricated as the sensor matrix to

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highly enlarge the specific surface area for fumigant enrichment so as to accelerate the

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detection reaction and lower the detection limit. The dynamic detection procedure is proposed

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to achieve a real-time monitoring of alkylating fumigants as well as other toxic alkylators in

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the environment.

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MATERIALS AND METHODS

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Chemicals and Materials

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4-(p-Nitrobenzyl) pyridine (NBP) (98.0%), and nylon-6 polymer pellets were purchased from

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ACROS Organics (NJ, USA). Methyl iodide (99.0%), methyl bromide (2000 µg/mL in

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methanol), and 1, 3-dichloropropene mixture isomers (5000 µg/mL in methanol) were bought

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from ACROS Organics, Restek Corporation (Bellefonte, PA, USA), and ULTRA scientific

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(Kingstown, RI, USA), respectively. All solvents used in this study were bought from Sigma-

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Aldrich Co. (Rocklin, CA, USA). All the chemicals are analytical grades and were directly

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used as received. Commercial glass microfiber filters and nylon membrane filters were

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purchased from GE Healthcare Life Sciences (Pittsburgh, PA, USA). The nylon-6 nanofibrous

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membrane was fabricated through electrospinning based on our previous method. 36

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Liquid Phase Detection

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The detection reaction in the liquid phase was monitored with an Evolution 600 UV-vis 4


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spectrophotometer (Thermo Scientific, USA) under a wavelength range of 430 nm‒800 nm.

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For the sample preparation, 1 mL of NBP solution (10%‒50%) was transferred into a quartz

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cuvette, and then fumigant solution was directly injected into the cuvette with a gas-tight

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syringe. After that, the cuvette was sealed immediately with a disposable cap and was scanned

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in the UV-vis spectrophotometer after different incubation durations (1‒30 min). The control

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sample was scanned before the injection of fumigants. The absorbance at the maximum

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absorption wavelength of 570‒590 nm was recorded to compare and evaluate the reaction rate

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and the detection sensitivity.

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Dynamic Gas Phase Detection

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Dynamic detection procedure is used in this study (Scheme 1a). A gas-tight syringe (Hamilton

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Co., NV, USA) was used as a gas chamber for fumigant vapor preparation. Fumigant solutions

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were injected into the syringe and let them evaporate into gases, then the tip of the syringe was

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connected to the sensor cell. The gas in the syringe was pumped through the sensor at a constant

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rate (500 mL/min), the total volume of the tested gas is 2.5 L for all detections. No extra

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incubation time is needed after the gas pumping, and the color of the sensor can be visually

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detection by naked eyes. To establish the relationship between fumigant concentrations and

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color intensities, a software called ColorAssist is applied to directly read the RGB values of

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the sensor through a smartphone (iPhone 7 Plus, Apple In., USA). All the sensors were scanned

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ten times to get an average number of R, G, and B values. The color difference between the

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sensor before and after fumigant exposure was calculated according to equation (1). The sensor

117

setups are shown in Scheme 1.

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𝐷𝑖𝑓𝑓. = (𝑅1 ― 𝑅2)2 + (𝐺1 ― 𝐺2)2 + (𝐵1 ― 𝐵2)2

(1)

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Where R1, G1, and B1 are the values in red, green and blue channels of the control group; R2,

120

G2, and B2 are the values in red, green and blue channels of the tested sensors.

121 122

Scheme 1. (a) Dynamic gas phase detection procedure. (b) Photos of sensor setups. 5



123

Gaussian Calculations

124

The geometry optimization of related compounds was performed with Gaussian 09 program

125

based on the density functional theory (DFT) with B3LYP/LanL2DZ basis set with conductor-

126

like polarizable continuum model (CPCM) solvent system or in the gas phase. The frequency

127

calculation of the optimized compound shows no imaginary frequency which confirms the

128

geometry energy is in a minimum state. The Gibbs free energy difference of the detection

129

reaction was calculated according to the Gibbs free energy of each compound in the frequency

130

calculation. All the viewing of the optimized geometries and the orbital images were performed

131

with GaussView 5.0.8.

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RESULTS AND DISCUSSIONS

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The Optimization of the Detection Reaction

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Traditionally, 4-(p-nitrobenzyl) pyridine (NBP) is designed and further explored for

135

monitoring alkylating reactions with a high-temperature incubation and the addition of extra

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bases such as sodium hydroxide or triethylamine, with the reaction shown in Figure 1. The

137

overall reaction mechanism is simple but is inconvenient to operate. In addition, the color

138

signal of the product is very unstable because of the presence of strong bases and the low

139

detection sensitivity.32 The same reaction is utilized here but with the addition of excess amount

140

of NBP in the system, which can serve as a base and drive the reaction moving to the formation

141

of the color product. The production of the color compound is monitored with UV-vis

142

spectrophotometer at λmax=570‒590 nm, with the λmax varied according to different alkylating

143

groups and solvent systems.14 The nucleophilic substitution reaction between NBP and

144

alkylating agents is proposed to be favored with a careful selection of solvents, NBP

145

concentrations, and incubation temperatures.

146

1, 3-Dichloropropene (1, 3-D) was used as a model alkylating fumigant for the

147

optimization of the detection condition. As shown in Figure 2(a), different solvent systems

148

present various rates of color generation. The higher the absorbance at λmax=570 nm illustrates

149

the faster the reaction rate between NBP and 1, 3-D. Obviously, 1, 3-D showed the outstanding

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reactivity with NBP in dimethyl sulfoxide (DMSO) system with a color intensity of 2.52 after

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30 min incubation at room temperature, whereas, the color intensities were dramatically

152

inhibited when acetonitrile (ACN), acetophenone (ACP), and isopropanol (IPN) were used as 6


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the solvents (Figure 2a). Here, DMSO was added to form 50/50 mixtures with ACN, ACP, and

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IPN to speed up the reactions since the color generation was very slow when only using these

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pure solvents. MeBr and MeI performed similarly as 1, 3-D toward NBP as another two

156

alkylating fumigants but with higher reactivities. The effects of the solvent system on the

157

detection of MeBr and MeI are available in the supporting information (Figure S1), which also

158

demonstrates the outstanding color generation in DMSO system.

159

The detection reaction shown in Figure 1 illustrates the needs of an extra base to abstract

160

one methylene-hydrogen atom from alkylated-NBP. Based on the chemical nature of NBP, it

161

can serve as not only a nucleophile to attack the alkylating agents, but also a potential base to

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complete the color generation. Therefore, an increased NBP concentration was used to

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accelerate the alkylation process and to directly trigger the color generation, and the results are

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shown in Figure 2(b). When the concentration of NBP was increased to 10% in DMSO, which

165

is much higher than that of the traditional method,18 the blue color was generated and enhanced

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with increasing the incubation time without addition of an extra base. Furthermore, the color

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intensity was dramatically improved with the increase of NBP concentration from 10% to 50%

168

(Figure 2b and Figure S2). The increment of NBP concentration kinetically accelerates the

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detection reaction rate for the achievement of an ultra-high detection sensitivity of 1, 3-D. And

170

excitingly, the concentrated NBP solution successfully eliminated the addition of extra base

171

during the detection process, making direct and rapid detection of 1, 3-D and other alkylating

172

fumigants by the naked eye according to the color change.

173

The temperature is another factor that can significantly affect the reaction rate. As the

174

results presented in Figure 2(c), when a trace amount of 1, 3-D was injected into the NBP

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system, very weak color change was generated after 15 min incubation at room temperature.

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However, the color intensity boosted to over 4.00 when the incubation temperature raised to

177

75 °C. Its color intensity can still reach 1.907 when the colored solution was diluted by 5 times

178

with DMSO (Figure 2c). The reaction rate has been significantly improved when the incubation

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temperature was increased to 75 °C, which is achievable with a portable heating pad in the

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practical use. The increment of the incubation temperature is another efficient way to further

181

improve the detection sensitivity.

7



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Figure 1. The detection reaction mechanism and the chemical structures of alkylating fumigants.

8


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185 186 187 188 189 190 191 192

Figure 2. (a) Solvent effects on the detection of 1, 3-D (50 µL 5 mg/mL) with 20% NBP in different solvents. The mixture solvents were prepared as the volume ratio of 1:1. The reactions were monitored at room temperature. (b) NBP concentration effects on the detection of 1, 3-D (50 µL 5 mg/mL) in DMSO solvent system. The reactions were monitored at room temperature. (c) UV-vis spectra of 1, 3-D (20 µL 5 mg/mL) detection with 50% NBP in DMSO with varied temperature and 15 min incubation time. 75 oC*0.2=five times dilution of the sample that was heated at 75 C for 15 min.

193

Demonstration of Extra NBP as An Internal Base and the Comparison of Fumigant

194

Reactivity

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The detailed reaction mechanisms between NBP and alkylating fumigants accompanied with 9



196

the addition of external or internal bases are presented in Figure 3. The detection mechanism

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of different fumigants relies on a nucleophilic substitution (NS) reaction followed with an

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abstraction of a methylene-H from the alkylated-NBP by a base. Previous results already show

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that the extra NBP facilitates the color generation as an internal base. However, a

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computational method is needed to theoretically prove the proposed function of NBP in the

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sensor system. In order to demonstrate the alkaline function of NBP in the sensing system, the

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thermodynamic properties of the reaction were calculated with the Gaussian program, and a

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traditionally-used base, NaOH, was calculated as a comparison. The leaving group (Cl‒) that

204

leaves from the first step of the reaction can also be a potential internal base in the reaction

205

system. The calculation results are shown in Figure 4.

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Firstly, the calculations of 1, 3-D detection with NBP were performed in different solvent

207

systems including gas phase, DMSO and acetophenone (ACP) as models to illustrate the

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function of solvents and the excess amount of NBP. The Gibbs free energy differences (∆G)

209

are plotted in Figure 4(a). Surprisingly, the NS process (step (1)) shows a significant energy

210

barrier in the gas phase with a ∆G1‒gas= +457.0 kJ/mol. The reaction will be dramatically

211

inhibited in the gas phase even that the second step reaction with OH‒ and Cl‒ is strongly

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spontaneous. Even worse, the H-abstraction (step (2)) seems not thermodynamically allowed

213

with extra NBP in the sensing system, where ∆G2‒gas is shown as +44.04 kJ/mol (Figure 4a).

214

When the reaction was performed in a solvent system, obviously, the ∆G1 dramatically

215

decreased to ‒7.30 kJ/mol and +10.58 kJ/mol in DMSO and ACP systems, respectively. Since

216

DMSO is more polar than ACP, it further favors the step (1) reaction and lowers the ∆G1 to

217

make it spontaneous at an ambient condition (Figure 4a). Nevertheless, the application of a

218

solvent system negatively affects the thermodynamics of the step (2) reaction when using

219

negatively charged bases, which results in around 400 kJ/mol increase of the ∆G2 (Figure 4a).

220

Furthermore, the calculation results proved that the leaving group (Cl-) is powerless to act as

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an internal base to make the color generation spontaneously. The lower ∆G2 of NBP as the base

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in the solvent systems is caused by the favorability of its transition state structure (TSS) to the

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polar solvent. The neutral NBP forms more polar TSS (separates the opposite charges in TSS)

224

with alkylated-NBP, which can be favored in a polar system. By performing the detection

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reaction in DMSO, the ∆G(1+2)‒DMSO/NBP was achieved to only +3.53 kJ/mol, which is almost 10


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spontaneous at ambient conditions, whereas, the H-abstraction still exists an energy barrier

227

(∆G2‒DMSO/NBP=10.83 kJ/mol) (Figure 4a and 4b). The calculation results of the detection of

228

MeBr and MeI in different solvent systems follow the same trend as 1, 3-D but show much

229

higher spontaneity (Figure S4).

230

Secondly, the thermodynamics of the detection reaction can also explain the reactivity

231

differences among 1, 3-D, MeBr, and MeI. The calculation results in DMSO system are

232

summarized in Figure 4(c). The total rxn refers to the ∆G(1+2) when NBP serves as the base in

233

step (2) reaction. The step (1) reaction of all the fumigants are spontaneous, and the reactivity

234

increases as the order of 1, 3-D < MeBr < MeI with a decreasing of ∆G1 from ‒7.30 kJ/mol to

235

‒55.97 kJ/mol (Figure 4c). However, the energy barrier presents on the H-abstraction step

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when using internal bases of X‒ or NBP (Figure 4c). Although the H-abstraction by NBP is not

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spontaneous, the total reactions are thermodynamically allowed by showing either very small

238

or negative values of ∆G(1+2)‒DMSO/NBP (Figure 4c).

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In conclusion, the thermodynamic calculations confirmed the importance of introducing

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DMSO in the sensor system to dramatically lower the energy barrier in the NS step.

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Furthermore, it demonstrated that the extra NBP is plausible to directly trigger the production

242

of color signals without the addition of a nonrecyclable base (NaOH or triethylamine).

243 244 245 246

Figure 3. The reaction mechanism of the detection of (a) 1, 3-D, (b) MeBr, and (c) MeI with NBP. The detailed reaction mechanisms in different base systems are available for 1, 3-D, the ones for MeBr and MeI are shown in the supporting information (Figure S3). 11



247 248 249 250 251 252 253

Figure 4. (a) Calculated Gibbs free energy differences of the NS reaction (1) and the Habstraction reaction (2) of trans-1, 3-D in different solvent systems with three types of bases: hydroxyl group, chloride ion, and NBP. (b) The Gibbs free energy differences of the overall reactions between 1, 3-D and NBP. (c) The Gibbs free energy differences of the fumigant detections in DMSO. The Total rxn refers to the ∆G of the total reaction when NBP serves as the base.

254

In the experimental test, interestingly, the color generations of MeBr and MeI detections

255

reached the equilibrium after 10 min incubation with significant color intensity difference. The

256

color intensity at equilibrium of MeI (2.62) is 1.87 times higher than that of MeBr (1.40)

257

(Figure 5a and 5b). Due to the same process of the second step of the detection of MeI and

258

MeBr, the reactivity difference observed in Figure 5(a) can be obviously explained as the effect

259

of different leaving groups in the chemical structures of MeI and MeBr. Computational

260

calculations were utilized to assist the analysis of the reactivity.

261

The NS reaction between NBP and alkylating fumigants can be analyzed as an electron

262

interaction between the highest occupied molecular orbital (HOMO) of NBP and the lowest

263

unoccupied molecular orbital (LUMO) of the alkylating fumigants based on the frontier

264

molecular orbital theory.37 The computational results are shown in Table 1 and Figure 5(c),

265

respectively. Methyl chloride (MeCl), 1-chloro-3-bromopropene, and 1-chloro-3-iodopropene

266

were calculated to assist in analyzing the leaving group effect. MeI presents the lowest LUMO 12


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energy (‒1.125 eV) and the smallest energy gap (5.995 eV) to the HOMO of NBP compared

268

with MeCl and MeBr (Table 1). The calculated reactivity of methyl halogens follows the order

269

of MeI > MeBr > MeCl, which is consistent with the experimental results (Figure 5a) and the

270

leaving ability of I‒, Br‒, and Cl‒. This changing trend was also proved by the calculations of

271

propene-based compounds by varying the substituent in 3-position from chloride to iodide. The

272

results and chemical structures are shown in Table 1. However, the narrower the energy gap

273

between NBP and 1, 3-D (5.677 eV and 5.595 eV) did not show better detection results than

274

either MeBr or MeI, which could be affected by the thermodynamics of the reaction and the

275

steric hindrance of cis- and trans-1, 3-D. As shown in Figure 5(c), the backside attack of NBP

276

toward cis- or trans-1, 3-D is highly inhibited by the п orbital of the double bond. The steric

277

hindrance and the thermodynamics of the reaction would significantly lower the reaction rate

278

between NBP and 1, 3-D, even though the kinetics of the reaction seems highly possible (Table

279

1).

280

Moreover, the electrostatic potential (ESP) maps are generated from GaussView. The high

281

electron density (red color in Figure 5c) on the nitrogen atom in the pyridine ring of NBP

282

illustrates the strong electron-donating ability and the nucleophilicity toward electrophilic

283

fumigants. It also shows the possibility of NBP to abstract a hydrogen atom from the alkylated-

284

NBP to complete the color generation during the detection.

13



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Figure 5. (a) Reactivity comparison of different alkylating fumigants according to incubation times. The concentration of NBP is 50% in DMSO. The molar amount of injected 1, 3-D is 10 times higher than that of MeI and MeBr in order to fit the detection range of the UV-vis spectroscopy. (b) The color images of the detection of (i) MeI, (ii) MeBr, and (iii) 1, 3-D. according to the increment of incubation time from 0 min to 30 min (from left to right). (c) Computational results of molecular orbitals and electrostatic potential maps of NBP and alkylating fumigants.

293

Table 1. The calculated orbital energy of NBP and alkylating agents. Compounds

Orbital energy (eV)

Orbital energy difference (eV)

Chemical structure NO2

NBP (HOMO) trans-1, 3-D (LUMO) cis-1, 3-D (LUMO) *trans-1-Cl-3-Br (LUMO) *trans-1-Cl-3-I (LUMO)

‒7.120

‒‒

‒1.443

5.677

‒1.525

5.595

‒1.733 ‒1.925

N

Cl

Cl

Cl

Cl

5.387

Br

Cl

5.195

I

Cl H

*MeCl (LUMO)

‒0.006

7.114

Cl

H H

14


Page 15 of 22 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


H

MeBr (LUMO)

‒0.619

6.501

Br

H H H

MeI (LUMO)

‒1.125

5.995

I

H H

294 295

* Chemicals were calculated as the model compounds for comparing the effect of the leaving group in alkylating fumigant structures.

296

Dynamic Gas Phase Detection

297

To detect alkylating fumigants in the gas phase, a large specific surface area and microporous

298

structure of the sensor matrix would highly assist the improvement of the detection sensitivity.

299

Nylon-6 nanofibrous membrane (N6NFM) was fabricated through electrospinning, and the

300

resulted material shows an average fiber diameter of 150 nm (Figure 6b-iv), which can

301

significantly facilitate the detection sensitivity of a gas sensor. To compare and prove the

302

outstanding effect of the surface area, different sensor matrices were applied to detect MeI (20

303

ppm) with a steady-state detection process (Figure S5), and the results are shown in Figure

304

6(a). Undoubtedly, N6NFM presented the highest color difference (∆E=87.79) of several folds

305

higher than that of the commercial nylon filter paper, the commercial glass microfiber filter

306

paper, and the liquid drop (Figure 6a). Interestingly, the detection sensitivity on different

307

matrices follows the order of the enlargement of the specific surface areas, which is achieved

308

by the decrement of the fiber diameter (Figure 6b). The sensor system based on the N6NFM

309

remarkably satisfied the fumigant sensor requirements of ultra-highly sensitive and portable.

310

To further improve the detection sensitivity and make our sensor system promise for real-

311

time monitoring, a dynamic detection process (Scheme 1) was developed. In this process, all

312

the fumigant molecules in a gas chamber are purged through a nanofibrous membrane filter

313

sensor in a known volume, concentration in ppm, and controlled speed. The total amount of

314

the fumigant in the volumes of the air is known and the exposure of the fiber surfaces to the

315

fumigant is enhanced, making the detection reaction kinetically favorable. The gas phase

316

monitoring of MeI, MeBr, and 1, 3-D was performed in the dynamic detection process by

317

loading 100 µL of optimized NBP solution on the N6NFM, and the results are shown in Figure

318

7. The naked-eye detectable color differences are easy to be achieved for MeI and MeBr

319

detections when their concentrations were changed from 0.5 ppm to 20 ppm. More excitingly, 15



320

the color differences at their permissible exposure limits reach to 80.73% (2 ppm of MeI) and

321

50.72% (1 ppm of MeBr) with only 5 min of exposure (Figure 7). Nevertheless, the slow

322

reaction rate between NBP and 1, 3-D at room temperature limits its detection sensitivity, and

323

the color differences were much weaker than that of MeI or MeBr. The naked-eye detection of

324

1, 3-D cannot reach to its PEL concentration (1 ppm) even with a prolonged operation time (10

325

min) (Figure S6).

326

However, a relatively high temperature would accelerate the color changes of 1, 3-D with

327

NBP. Then, the detection of 1, 3-D was successfully achieved at a higher temperature by

328

placing the sensor cell into a 65±2 °C oven while doing the dynamic detection process. The

329

detection limit has been effectively improved with a naked-eye readable signal at the

330

concentration of 0.8 ppm, and the color difference at its PEL concentration (1 ppm) was shown

331

as 49.33%, which is 5.23 times higher than that of at the room temperature (Figure 7c and

332

Figure S6).

333

Overall, the relationship between fumigant concentration and color difference is plotted to

334

obtain the linear range of the detection (Figure S8). The linear detection ranges of MeI, MeBr,

335

and 1, 3-D are 0.5 ppm‒5 ppm, 2 ppm‒20 ppm, and 2 ppm‒20 ppm, respectively. Because of

336

the fastest reaction rate of MeI detection, the color intensity of the tested samples became

337

saturated when the fumigant concentration is over 5 ppm, whereas, the linear ranges of MeBr

338

and 1, 3-D are achieved at a higher concentration levels (Figure 7 and Figure S8).

16


Page 16 of 22

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339 340 341 342 343 344 345 346

Figure 6. (a) Color differences after the steady-state detection procedure of 20 ppm MeI detection on different sensor matrices. The color images on the right column were generated from PhotoShop CS6 based on the RGB values of the sensor before and after fumigant exposure. The exposure time was 10 min. (b) The photo and SEM images of sensor matrices (i) liquid drop, (ii) glass microfiber filter paper, (iii) nylon filter paper, and (iv) nylon-6 nanofibrous membrane. The fiber diameter distributions are shown in Figure S9 in supporting information.

347 348 349

Figure 7. Color differences and sensor images of gas phase detection of alkylating fumigants: (a) and (b) MeI, (c) and (d) MeBr, (e) and (f) 1, 3-D. The volume of the gas is 2.5 L with a 17



350 351

pumping rate of 500 mL/min. The results of 1, 3-D detection were obtained at a higher temperature of 65 °C. * refers to the permissible exposure limit (PEL) of each fumigant.

352

CONCLUSION

353

In this study, a modified colorimetric detection system for reacting alkylating fumigants with

354

4-(p-nitrobenzyl) pyridine (NBP) was successfully applied in detecting MeI, MeBr, and 1, 3-

355

D by showing a naked-eye detectable signal with a concentration at a ppb to ppm level. Based

356

on the experimental and computational analyses, DMSO was found to be indispensable and

357

optimal to greatly improve the detection sensitivity. More importantly, the extra amount of

358

NBP was proved to serve as the internal base to make the nucleophilic substitution and the

359

color generation occur in one step. Nylon-6 nanofibrous membrane provides an ultra-high

360

surface area and porous structure for attracting and concentrating the fumigant molecules

361

during the pumping of the tested gases with the assistance of DMSO. The detection limits of

362

MeI, MeBr, and 1, 3-D were found at 0.5 ppm, 0.5 ppm, and 0.8 ppm, respectively, which are

363

all lower than their safety requirements, and the color signals are readable by the naked eye.

364

The dynamic detection process shows a possible way for a real-time monitoring of fumigant

365

concentrations in the practical uses to improve the personal protection from the overexposure

366

of the carcinogenetic alkylating fumigants.

367

ACKNOWLEDGMENT

368

This work is financially supported by the California Department of Pesticide Regulation,

369

Environmental Protection Agency. We would like to thank Keck Spectral Imaging Facility in

370

the Department of Chemistry at the University of California, Davis for providing the access to

371

the SEM. We would like to thank Miss Sanaz Ghanbari, and undergraduate students Maria

372

Trinidad Gomez and Mr. Vu Vu at the University of California, Davis for their efforts on the

373

preliminary studies of this work.

374 375 376 377 378 379 380 381 382

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Colorimetric Detection of Carcinogenic Alkylating Fumigants on Nylon

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