Selective Reagent Ions for the Direct Vapor Detection of

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Selective Reagent Ions for the Direct Vapor Detection of Organophosphorus Compounds Below Part-Per-Trillion Levels Robert G. Ewing, and Blandina R. Valenzuela Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.8b01265 • Publication Date (Web): 29 May 2018 Downloaded from http://pubs.acs.org on May 29, 2018

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Analytical Chemistry

Selective Reagent Ions for the Direct Vapor Detection of Organophosphorus Compounds Below Part-Per-Trillion Levels Robert G. Ewing* and Blandina R. Valenzuela Pacific Northwest National Laboratory, 902 Battelle Blvd., Richland, WA 99352, United States

Abstract Real-time low to sub parts-per-trillion vapor detection of some organophosphorous compounds (OPCs) is demonstrated with an atmospheric flow tube – mass spectrometer. The chemical species investigated included dimethyl methylphosphonate, triethyl phosphate and tributylphosphate. The atmospheric flow tube provides ambient chemical ionization with up to several seconds of ionization time. With sensitivities in the ppqv range, there are many background contaminants competing for charge with the target analytes. Initially, the OPCs were not observable in direct room air analysis presumably due to other trace components possessing higher proton affinities. However, the addition of a trialkylamine as a dopant chemical served to provide a single reagent ion that also formed a proton-bound heterodimer with the OPCs. These asymmetric proton-bound dimers had sufficiently high hydrogen bond energy to allow the cluster to remain intact during the analysis time of several seconds. Changes in stability were observed for some of these asymmetric proton-bound dimers with a shorter half-life for adducts with a larger proton affinity differences between the amine and the OPC. Detection levels approaching low ppt to high ppq were correlated by 3 different methods including use of a permeation tube, direct injection of a fixed mass into the sample air flow, and calculations based upon signal intensity ratios, reaction time and an estimated reaction rate constant. A practical demonstration showed real-time monitoring of a laboratory environment initially with low ppt levels of vapor observed to decay exponentially over about an hour while returning to baseline levels.

Key words: Atmospheric flow tube, selective ambient ionization, organophosphorous detection

*Corresponding Author: [email protected]

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Introduction Organophosphorous compounds (OPC) are used primarily in many herbicides and pesticides as a replacement for the environmentally persistent chlorinated hydrocarbons. The lethal nature of OPCs as insecticides transfers to humans, making them effective chemical warfare nerve agents (e.g. sarin and VX). The Centers for Disease Control’s (CDC's) final recommendations for protecting human health from potential adverse effects of exposure to nerve agents in 2008 listed limits ranging from 6x10-7 to 1x10-6 mg/m3 (roughly 0.1 pptv) in the general population.1 At these extremely low levels of toxicity, there is a need for a corresponding detection capability. Due to high toxicity of many organophosphorous pesticides, the Environmental Protection Agency (EPA) has dramatically decreased, restricted, or banned their use over the past 15 years.2 Organophosphorous compounds can be found in a variety of complex matrices requiring clean-up as well as separation to improve their detection. These analytical techniques range in application from colorimetric techniques3 using impregnated paper strips to rapidly identify residual droplets to spectroscopic techniques to identify gas plumes at kilometer distances.3,4 Intermediate to these two applications is the ability to monitor ambient air for vapor detection and identification, with a variety of technologies available for direct vapor monitoring. Due to the relatively large number of collisions occurring at ambient pressure, atmospheric pressure chemical ionization (APCI) provides low detection levels for a variety of organic compounds. Two technologies incorporating ambient ionization are mass spectrometry and ion mobility spectrometry with tradeoffs occurring between resolution and selectivity of the former versus portability and simplicity of the later. The sensitivity of APCI results from the high number of collisions; however, this also presents either a challenge or an advantage. Chemical ionization favors the analyte with the highest charge affinity resulting in selective ionization. As a result, some analytes may pose a challenge for detection while others can be detected in relatively complex matrices. Favorable ionization chemistry combined with increased sensitivity in ambient ionization are needed to achieve general population limits of detection of OPCs. The recent development of atmospheric flow tube – mass spectrometry (AFT-MS) enabled vapor detection of some explosive compounds at parts-per-quadrillion (ppqv) levels.5,6. This technology incorporates a long reaction region operated at atmospheric pressure that affords reactions times up to several seconds providing a significant increase in the number of ion-molecule collisions thus achieving ppqv detection levels. Other techniques use reaction regions operated at a few Torr to achieve pptv sensitivity, these include selected ion flow tube-mass spectrometry (SIFT-MS)7 and proton transfer reaction-mass spectrometry (PTR-MS)8,9. The following equation describes the relationship between concentration, reaction time, and ion signal. [A−] = [R−]0[A]kt In Eq. 1, k is the reaction rate constant (typically > 10−9 cm3 molecule−1 s−1), t is the reaction time in seconds, [A] is the concentration of the analyte, [A−] is the concentration of the analyte ions (proportional to measured signal), and [R−]0 is the initial reactant ion concentration (measured signal). 2 ACS Paragon Plus Environment

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Selectivity for vapor detection of explosives with the AFT-MS was achieved by using nitrate reactant ions.6 For compounds likely to form protonated positive ions, a suitably selective reagent ion with a high proton affinity will be required as sensitivity increases and the number of contaminants present in room air at ppt or ppq levels also increases.10 Dopants, analytes, or other molecular species (e.g. contaminants) introduced into the ionization region may be ionized. The main ionization process for positive ion production at atmospheric pressure involves proton transfer from a reagent ion to the analyte ion. In this process, the molecular species with the highest proton affinity retains the charge and is observed. An additional ionization process involves adduct formation between a protonated species and an analyte. Presented here is the demonstration of the real-time, sub-ppt detection of levels of OPC vapors with AFT-MS using trialkylamines as a dopant to produce selective reagent ions.

Experimental Instrumentation: The instrument used is an API-5000 triple quadrupole mass spectrometer (AB-Sciex, Framingham, Massachusetts). The factory supplied ionization source as well as the interface plate were removed and replaced by a custom built atmospheric flow tube (AFT). The orifice voltage (DP) was held at a minimum value of +5V with the interface heater off. The AFT is described in detail in previously published articles5,6,11 with slight modifications. A diagram of the AFT-MS is provided in the Supporting Information (S2). In summary, the reaction region of the AFT consisted of a 71 cm long x 1-inch OD copper tube maintained at ambient temperature and pressure with an ionization source at one end and the mass spectrometer orifice at the other. A dielectric barrier discharge was used as the ionization source and was operated in air at ambient pressure. The ion source was positioned in the center of the tube with a 1-inch tee. The exit of the tube was inserted through a vacuum coupling into a cylindrical aluminum housing which was fastened onto the front end of the mass spectrometer. The reaction region was held at ground potential and inserted into the aluminum housing so that the end of the tube was approximately 0.5 cm away from the orifice of the mass spectrometer. Suction was applied to the aluminum housing through a 1/8-inch port providing a variable flow rate maintained at about 6 L/min. As a result of the applied suction, ions were drawn down the tube, from the ionization source to the inlet of the mass spectrometer by the bulk air flow with an approximate transit time of 3 seconds. Ions were transferred into the mass spectrometer through the 0.6 mm orifice. Data Collection: Spectra were collected as either full scan mass spectra or selected ion monitoring (SIM) plots of individual ion intensities. Full scan mass spectra were collected as a qualitative measure to determine which product ions were formed. SIM, a more sensitive method, was used to determine relative responses and approximate detection levels of the various analytes. In SIM mode, a dwell time of 200 ms was used for each ion. In some instances, data was smoothed by using a rolling average of 5 data points. Vapor Introduction: Sample vapors were introduced into the inlet of the AFT in the presence of laboratory room air. Ambient conditions within laboratory varied slightly from day to day with pressures of about 750 torr, temperatures ranging from 18 to 24°C and relative humidity ranging from 15 to 35 3 ACS Paragon Plus Environment


%RH. The suction applied to the aluminum housing drew in both ambient air and trace sample vapors past the ionization source and into the reaction region towards the inlet of the mass spectrometer. Trace levels of sample vapors were introduced at the inlet of the AFT from a permeation source. The chemicals dimethyl methylphosphonate (DMMP), tributyl phosphate (TBP), triethylamine (TEA) and tributylamine (TBA) were purchased from Sigma Aldrich (St. Louis, MO, USA) at 98+ % purity. Approximately 0.5 mL of these chemicals were placed individually into 2 mL vials with caps containing unpunctured Teflon coated septa (Restek, Bellefonte, PA). These vials were allowed to stand for several weeks to ensure vapor was a result of permeation and not from residual chemical emanating from around the cap or threads of the vial. Triethyl phosphate (TEP) was obtained as a sealed commercial permeation tube from Metronics Dynacal (Poulsbo, WA, USA part # 100-010-7850-U50). The TEP permeation tube was about ¼ in. diameter tubing 1 cm in length with a projected permeation rate of 5 ng/min ± 50% at 50 °C. For TEP experiments, purified air at a flow rate of 6 L/min was used instead of room air. This enabled a better estimation of detection limits by providing a measurable flow rate with low humidity and minimal contaminants. For these experiments the dopant (trialkylamine) was placed directly inside the opening of the AFT and the purified air was then attached to the front sealing off the system from outside air. Downstream from the dopant but in front of the ionization source, the TEP permeation tube was introduced via a 1-inch tee. For direct vapor detection, a permeation tube was placed at the inlet of the AFT with emanating vapors being drawn into the reaction region and entrained with room air. In cases where two chemicals were introduced, one permeation tube (serving as the reagent) was placed inside the inlet to the AFT while the other (serving as the analyte) was brought up to the inlet. Both permeation tubes were upstream of the ionization source. Thermal Desorption: Direct thermal desorption measurements were carried out by placing a 1 μL aliquot of a sample dilution in methanol onto a Nichrome wire coil and positioning the coil into the center of the inlet to the AFT. The methanol solvent was allowed to evaporate for 1 minute followed by desorption of the analyte by applying an electric current to resistively heat the coil. The coil was fabricated from 0.254 mm O.D. wire (60% nickel, 16% chromium, 24% iron). The coil itself is approximately 6 mm wide with a 4mm OD containing approximately 10 coils in total with two wire leads that were connected to a variable voltage DC power supply (0-30 V, 2 A). The overall resistance of the coil and leads was 9.7 ohms. The application of 10 V resistively heated the coil producing approximately 1 A of current. The desorbed analyte vapors along with the dopant (trialkylamine) vapor from the permeation tube (residing inside the inlet) were drawn into the AFT past the ionization source and to the inlet of the mass spectrometer.

Results and Discussion The sensitivity of the AFT-MS for the vapor detection of compounds at low ppq levels led to the investigation of organophosphorus compounds by this same technique with positive ions. The detection of DMMP vapor was first attempted by monitoring the positive ion mass spectra. To our surprise, direct 4 ACS Paragon Plus Environment

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detection of DMMP was not apparent in the spectrum. Neither the protonated monomer nor the proton-bound dimer of DMMP was observed even at moderate vapor concentrations. This was unexpected because DMMP has a relatively high proton affinity (PA) and normally responds well with various ambient ionization techniques. Observation of the positive ion mass spectra generated from room air revealed a variety of peaks across the spectrum as shown in Figure 1A, in which appears a group of ions between 70 and 120 amu as well as other larger ions above 200 amu. Of note is that most of the ion species are observed at even mass units (e.g. m/z of 74, 88 and 118). Since protonation reactions produce M+1 masses, the neutral species must have odd molecular weights; this is typically observed for organic species containing odd numbers of nitrogen atoms. Moreover, amine compounds have relatively high proton affinities and consequently may well be the source of the observed ions in the spectra. With the sensitivity of the AFT-MS, these compounds could be present in room air at ppq levels and still show a significant response. The presence of these amines may be the reason why the protonated DMMP ion was not observed in Figure 1B at m/z 125 in that the higher PA amines would preferentially become protonated relative to DMMP. For example, the PA of n-butylamine is 921.5 kJ/mol12,13 whereas the PA of DMMP has the reported values of 91114, 90215 and 89816 kJ/mol with an average value of 904 kJ/mol.

Figure 1. Mass spectra of A) background air, B) dimethyl methylphosphonate vapor, C) triethylamine vapor, and D) both dimethyl methylphosphonate and triethylamine vapor. Proton Affinity of Amines: The PA of amines increases with an increase in the alkyl chain length on the nitrogen atom, for example, the PA of methylamine (899 kJ/mol) is less than that of hexylamine (927.5 5 ACS Paragon Plus Environment


kJ/mol).12 The PA of amines also increases as more alkyl groups are added on to the nitrogen atom as depicted in the following examples: hexylamine (927.5 kJ/mol) < dipropylamine (962.3 kJ/mol) < triethylamine (981.8 kJ/mol).12 To better understand the ions that may be present in the spectra, nhexylamine vapor was introduced at the inlet to the AFT-MS along with room air but no response was observed (data not shown). From this data, a conclusion could be drawn that the peak at m/z 74 is not from protonated n-butylamine, but likely a higher substituted amine such as diethylamine or dimethylethylamine, both of which have greater PAs than n-hexylamine but the same molecular weight. Triethylamine dopant: To test this theory, triethylamine (TEA), which has a higher PA than diethylamine or dimethylethylamine, was introduced to the inlet of the AFT, resulting in a strong peak observed at m/z 102 for protonated TEA as shown in Figure 1C. The TEA peak appears to dominate the spectra indicating it has a higher PA than other contaminants present in the room air. The combination of these results suggests amines are likely present in the room air and these contaminants have PA values greater than DMMP but less than TEA. The concentration of TEA is unknown, but based upon previous work with explosive vapors the concentration is likely in the high ppq to low ppt range. This approximate concentration is also supported by the detection of TEA vapor out of a sealed vial with an unpunctured, Teflon lined septum. The permeation rates are too low to easily quantitate by gravimetric measurements. For example, a concentration of 1 ppt TEA would require a mass loss of ~24 pg/min into a flow of 6 L/min. A vial losing 24 pg/min would lose about 1 µg in 30 days, a level not gravimetrically measurable in our laboratory. Regardless of the actual concentration, the vapors were at trace yet sufficient levels for the protonated TEA monomer to dominate the spectra. Atmospheric pressure ionization for positive ions typically involves proton transfer with protonated reagent ions transferring the proton to an analyte with a higher PA. The addition of reagent chemicals has been used as a means of selective ionization by producing a reagent ion having a higher PA than potentially interfering background species such as hydrocarbons, alcohols, and other organic species.10,17,18 The reagent ion will only transfer its proton to an analyte of higher PA. Aside from proton transfer, another possible ionization mechanism involves adduct formation. Many polar organic species will form both homogeneous and heterogeneous proton-bound dimers.14 Although the TEA in the AFT with room air provides a dominant protonated TEA monomer (Figure 1C), it seemed unlikely to act as a reasonable reagent ion for OPCs for two reasons: 1) higher PA values, proton transfer will not occur and 2) steric hindrance, adduct formation seem unlikely with many species. The unlikelihood of clustering is demonstrated by the lack of a proton-bound TEA dimer in the spectra of Figure 1C and in other work19. Additionally, the lack of clustering with water has resulted in the suggestion of using highly substituted amines or pyridines as standards in IMS since their mobility is relatively independent of moisture levels.20-22 Although TEA was thought to be an unlikely reagent ion, the spectra in Figure 1D shows the appearance of the TEA-DMMP proton-bound heterodimer at m/z 226. This was confirmed by MS/MS with fragmentation of m/z 226 producing m/z 102, the TEA monomer. A closer inspection of Figure 1B shows a small peak at m/z 226 representing the TEA-DMMP proton-bound-dimer. This likely results from the trace presence of the TEA protonated monomer also observed at m/z 102 in the background spectra. For Figure 1D, the sealed vials of TEA and DMMP were placed in the inlet to the AFT leading to the detection of DMMP by the formation of the TEA∙H+∙DMMP 6 ACS Paragon Plus Environment

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adduct. Details of the ionization chemistry related to using secondary and tertiary amines as reagents for organophosphorus compounds will be discussed below. An approximate DMMP concentration was estimated using Equation 1. The TEA intensity of 27,457 counts per second (cps) from Figure 1C was used for [R-]o and the DMMP response of 7,834 cps from Figure 1D was used for A-. An approximated reaction rate constant of 2.0x10−9 cm3 molecule−1 s−1 and a reaction time of 3 seconds (the transit time from source to detector) provided an estimated DMMP concentration of 4.8x107 molecule/cm3 or about 2 pptv. Tributylamine dopant: A similar set of data was collected using a different amine, tributylamine (TBA), and a second organophosphorus compound, tributylphosphate (TBP). This data is presented in Figure 2. The background spectra for room air (shown in Figure 2A) was about the same as that shown in Figure 1A. To accommodate for the higher molecular weight of TBP (266 amu), the x-axis displayed in Figure 2A ranges from m/z 150 to 450. When the vial containing the TBP was brought to the inlet of the AFT-MS (Figure 2B), no response was observed for the protonated monomer which is expected to appear at m/z 267. When the vial containing TBA was brought to the inlet of the AFT-MS, a significant response for the protonated monomer was observed at m/z 186. Similar to TEA, TBA appears to gather most of the charge and become the predominant ion in the spectra shown in Figure 2C. When both vials of TBA and TBP are brought to the inlet of the AFT-MS simultaneously, a significant response for the TBP was observed as the proton-bound TBA-TBP adduct as displayed in Figure 2D. The TBP concentration was estimated to be about 8 pptv using Equation 1 and the same k and t used above for DMMP. This value is deemed less reliable since the TBP intensity of 148,323 cps is greater than the reagent ion TBA intensity of 128,317 counts per second (cps). For the equation to be useable, the analyte ion should be small (i.e. less than 10%) compared to the reagent ion. Although the value of 8 pptv is only an estimate, it does provide an order of magnitude approximation for the TBP concentration.



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Figure 2. Mass spectra of A) background air, B) tributyl phosphate vapor, C) tributylamine vapor, and D) both tributyl phosphate and tributylamine vapor. The use of highly substituted amines such as trialkylamines (TAA) as reagent chemicals for selective ionization of organophosphorus compounds initially seemed unfavorable due to the relatively high proton affinities. The high proton affinities certainly lend to a high selectivity, however the PA affinities of the TAAs were higher than the OPCs. Thus, proton transfer from the TAA to the OPC will not occur, leaving only the possibility of adduct formation by the association of a protonated molecule AH+ with a neutral molecule B. AH+ + B + M → ABH+ + M

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Binding Energies and Predicted Half-Lives: Standard enthalpies of association of symmetrical protonbound dimers for oxygen bases are constant at 134 ± 6.3 kJ/mol23 and standard enthalpies of formation of symmetrical proton-bound dimers for nitrogen bases are constant at 96 +/- 6.3 kJ/mol24-26. Linear correlations between standard enthalpies of binding and the differences in proton affinity for the compounds in asymmetrical proton-bound dimers allow for a method of estimating the hydrogen bond energies of various asymmetrical proton-bound dimers. Adjustment of the proton affinity values to a later evaluated scale13 leads to the following parameters (a in kJ/mol, b dimensionless) for the linear correlations, ΔH0 = a – b X ΔPA: –NH+ ∙∙∙O–, (125.9 ± 2.5, 0.25 ± 0.01), –OH+ ∙∙∙O–, (123.4 ± 2.5, 0.27 ± 0.02), –NH+ ∙∙∙N–, (96.2 ± 4.2, 0.22 ± 0.06) as reported previously14. These parameters were used to estimate the enthalpy changes for the formation of the hydrogen bonds and are listed in 5th column of Table 1. Measured entropy changes for hydrogen bond formation of various –NH+ ∙∙∙O– proton-bound 8 ACS Paragon Plus Environment

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dimers range from approximately 80 to 125 J mol-1 K-1 24. A constant ΔS0 value of 30 cal mol-1 K-1 or 125.5 J mol-1 K-1 was chosen along with the calculated enthalpy changes for calculations of ΔG0. The equilibrium constant K was obtained from ΔG0 and subsequently the dissociation rate constant k– using Equation 3 where P0 is the standard pressure of one atmosphere. A selected value of 2.0x10-9 cm3 mol-1 s-1 was used for the association rate constant k+ assumed to be near the collision rate constant at atmospheric pressure. ‫ି ݁ = ܭ‬௱ீ

బ /ோ்

=

௞శ ଴ ܲ ௞ష

3)

The dissociation rate constant k– is provided in column 6 of Table 1 along with the half-lives in column 7 derived from these first order rate constants. Table 1. Proton affinities, calculated enthalpy change for the hydrogen bond in AHB+, and calculated half-lives of proton-bound dimers. A TEA TEA TEA TBA TBA TBA

B DMMP TEP TBP DMMP TEP TBP

Proton affinity A -1 a kJ mol 981.8 981.8 981.8 998.5 998.5 998.5

TEA TBA

TEA TBA

981.8 998.5

Proton affinity B -1 a kJ mol c 904 909.3 d ~925 c 904 909.3 d ~925

0

-ΔH -1 b kJ mol 106.5 107.8 111.7 102.3 103.6 107.5

-1

k- (s ) 4.2E-02 2.5E-02 5.0E-03 2.3E-01 1.3E-01 2.7E-02 e

---

96.2 (99.6 ) e 96.2 (102 )

e

2.6E+0 (1.8E+2 ) e 2.6E+0 (1.5E+5 )

t1/2 (s) 17 28 138 3 5 26 e

0.26 (3.9E-3 ) e 0.26 (4.6E-6 )

Data from ref 13 unless otherwise stated Calculated enthalpy change for the formation of the hydrogen bond in AHB+ Average PA for DMMP14-16 Estimated PA of tributyl phosphate from trimethyl phosphate = 890.6 kJ/mol12 and triethyl phosphate = 909.3 kJ/mol12 e) Based upon measured values of -ΔH0 and ΔS0 from Meot-Ner and Sieck26 (ΔS0 = 172 J mol-1 K-1 for TEA and 236 for TBA) a) b) c) d)

By selecting a constant ΔS0 value for the calculations of the half-lives, any differences will be linked directly to differences in the calculated hydrogen bond energies. As expected, an increase in the proton affinity of the OPC for a given TAA results in a lower ΔPA, a stronger bond and a longer half-life. Of the 6 combinations of –NH+ ∙∙∙O– proton-bound dimers all had half-lives of 3 seconds or greater. With a reaction time of about 3 seconds, even adducts formed at the beginning of the ionization source should have a 50% or greater population surviving to the orifice of the mass spectrometer. The OPC adducts formed with TEA will result in a more stable (longer lifetime) ion than the OPC adducts formed with TBA. Additionally, of the OPCs studied, TBP produced the most stable adduct with a given amine due to its relatively higher PA. In the approach to equilibrium in ion-molecule reaction kinetics, at reaction times much shorter than the half-life, the ratio ABH+/AH+ is determined by the k+. With reaction times much longer than the half-life the ratio is determined by the equilibrium constant. In the absence of other 9 ACS Paragon Plus Environment


competing reactions, the ratio ABH+/AH+ will provide a more robust measure of the analyte concentration over that of the analyte signal alone. The TBP results listed in Table 1 are rough estimates in the absence of a measured PA. The estimate PA value of 925 kJ/mol is based upon increasing PA values with increases in the alkyl chain length on a given base, and at a broad level the PA of TBP > TEP. This was further refined based upon the incremental increase in PA of about 20 kJ/mol from trimethyl phosphate to TEP and a similar relationship for the trialkylamines. The increase in PA between trimethylamine and TEA is ~33 kJ/mol and the difference between TEA and TBA is ~17 kJ/mol.12 Although not exact, the estimated PA for TBP of 925 kJ/mol seems reasonable for comparison purposes described here. The additional data in Table 1 provides for estimates of the half-lives of the symmetrical proton-bound dimers of TEA and TBA. The first numbers are a result of the calculated values and were based upon a -ΔH0 value of 96.2 kJ/mol and a ΔS0 value of 125.5 J/mol∙K. These calculations resulted in estimated lifetimes of ~0.25 s for both TEA and TBA. Moet-Ner and Sieck noted the abnormally high values for ΔS0 of trialkylamines and substituted pyridines.26 Using their measured values resulted in half-lives of 3.9x10-3 s and 4.6x10-6 s for the protonbound dimers of TEA and TBA, respectively. The calculations based upon the measured values of -ΔH0 and ΔS0 are given in parentheses in Table 1. These values correlate with the absence of any appearance of the proton-bound dimer in the spectra here or in ion mobility spectra27 where drift time are on the order of several to tens of milliseconds. Investigations into ion mobility studies of a series asymmetric proton bound dimers demonstrated that the asymmetric dimers were typically not observable when the calculated half-lives fell below 1 second.14 Although these calculations are estimates, they demonstrate a direct correlation between hydrogen bond strength and half-life which can be used as a tool to predict which ion clusters may be observable in a given technique with a known reaction time. The presence of moisture in the supporting air can result in hydrated ions allowing a displacement reaction involving the water. This could result in lowering the activation energy for the dissociation of the proton-bound dimer.27 This could affect the observed lifetimes of the ions and the moisture level of the gas in the reaction region should be considered. Quantitation of Vapor: Prior experience with the AFT-MS on explosives vapor detection along with concentration estimates discussed for Figures 1 and 2 suggest detection limits may be in the parts-perquadrillion level (ppqV) for the OPCs using TAAs as reagent ions. To explore the quantitative aspects, a commercially available TEP permeation tube with an emission rate of 5 ng/min ± 50% at 50 °C was used as a vapor source. For these experiments, a vial containing the dopant chemical (TEA or TBA) was placed into the inlet of the AFT, the TEP permeation tube was introduced via a tee, both upstream of the ionization source as described in the Experimental Section. Clean air was provided at 6 L/min in lieu of room air. The mass spectrometer was operated in SIM mode to monitor the TEA∙H+∙TEP adduct at m/z 284 or the TBA∙H+∙TEP adduct at m/z 368. Data collection was initiated to establish a baseline followed by the introduction of the TEP permeation tube to the inlet for 15 seconds after which it was removed. Data for vapor detection of TEP with both TBA and TEA dopants is presented side by side in Figure 3. Introduction and removal of the TEP results in a relatively fast response and clear down of the signal. TEP with the TBA dopant present resulted in a signal intensity of about 5291 ± 741 cps and a signal intensity of about 8244 ± 848 with the TEA dopant present. The TEP permeation rate of 5 ng/min ± 50% 10 ACS Paragon Plus Environment

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was designed for a temperature of 50 °C. At this emission level with a flow rate of 6 L/min, the concentrations would be in the range of ~ 56 to 170 pptV. However, the permeation tube was held at room temperature (~20 °C) which will result in a lower permeation rate. Since the actual value is unknown, the concentration was estimated to decrease by 50% for every 10 °C drop. Using this estimation, the approximate concentration would be between 7 and 21 pptV.

Figure 3. Selected ion monitoring of the proton-bound heterodimer of triethyl phosphate and tributylamine at m/z 368 (left) and triethyl phosphate and triethylamine at m/z 284 (right). In both cases the amine dopant remained with the inlet with 6 L/min purified air flow and the triethyl phosphate was introduced and removed through a tee upstream of the ion source at the indicated times. Quantitation by Thermal Desorption: An additional approach to quantitation is presented in Figure 4. In this experiment the dopant vial (TEA or TBA) was placed into the inlet of the AFT as described for Figure 3. The TBP analyte, however, was introduced by placing a 1 µL solution of methanol containing TBP onto a wire filament. The filament was placed inside the inlet to the AFT and the methanol was allowed to evaporate for 30 seconds prior to heating the filament to desorb the TBP. This method of desorption was described in greater detail for explosives detection.11 Both 6 pg and 24 pg of TBP were desorbed with the TBA dopant (Figure 4A) or with TEA dopant (Figure 4B). The peak widths of these spikes are approximately 6 seconds wide and at a flow rate of 6 L/min, which represents an air volume of about 0.6 L. The vapor concentration of 6 pg in 0.6 L is about 900 ppqV. Although this number may not be exact, the results here and from the TEP permeation tube indicate detection limits in the high parts-perquadrillion level. These detection levels appear to be higher than the approximate 10 ppq levels 11 ACS Paragon Plus Environment


observed previously for explosive vapors using this same AFT-MS. The slightly reduced detection levels may be partially related to the need to first form the reactant ion species of the trialkylamine prior to forming the adduct while traversing the reaction region.

Figure 4. (4A) Selected ion monitoring of the proton-bound heterodimer of tributyl phosphate and tributylamine at m/z 452. (4B)Selected ion monitoring of the proton-bound heterodimer tributyl phosphate and triethylamine at m/z 368. In both cases the amine dopant remained with the inlet while a fixed mass of TBP was desorbed. The data shows the response for desorbing both 6 pg and 24 pg of TBP. An interesting observation was noted in the OPC proton-bound adduct signal intensity. The response appears to be larger when using TEA as the dopant compared to using TBA as a dopant (see Figures 3 and 4). One possible explanation is the TEA concentration is higher than that of TBA. This could occur if the permeation rate for TEA is higher than that for TBA. With more dopant ion available the signal for the proton-bound adduct should be larger for the same OPC vapor concentration. In a separate experiment (data not shown), DMMP and TBP vapors from sealed vials were examined separately with both TEA and TBA dopants. The same trend was observed where the OPC adduct was larger with the TEA dopant than with the TBA dopant. Interestingly, the intensity of the protonated dopant prior to the addition of the OPC showed that the protonated TEA monomer was about half the abundance of the protonated TBA monomer. This observation indicates that the intensity of the TEA adducts with an OPC are higher than the TBA adducts despite the initial smaller intensity of the TEA reactant ion. A likely explanation of this observation is TEA has a lower proton affinity than TBA, which results in a larger hydrogen bond energy and subsequently a longer half-life for the TEA-OPC proton-bound dimer. The shorter half-lives for the TBA adducts are approaching the time the ions spend in the reaction region, consequently, some of the TBA-OPC adduct ions may be dissociating prior to reaching the mass spectrometer resulting in a reduced signal.


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Vapor Detection in a Laboratory: A demonstration of the sensitivity and the capability for real-time monitoring of air quality is provided by the desorption of trace levels of DMMP vapor into an unoccupied laboratory. The 706 ft2 laboratory with a ceiling height of 8 ft has a total volume of 5650 ft3 (160 m3). The fume hood provides a venting air flow of 230 cfm (6.5 m3/min). A filament, as described for Figure 4, was placed on a laboratory bench ~4 meters from the AFT-MS inlet. Three separate experiments were performed by depositing 1 µL of 3 different concentrations of DMMP onto the filament. The three different amounts deposited were: 1) a 1:100 dilution of DMMP in methanol, 2) a 1:10 dilution of DMMP in methanol, and 3) neat DMMP solution representing 11.5, 115, and 1150 µg respectively. Assuming complete mixing in the laboratory without any losses to the walls or ventilation from the hood, these amounts represent a maximum concentration of 14 pptv, 140 pptv, and 1.4 ppbv. The vial containing the TEA dopant was placed in the inlet of the AFT and data collection was initiated while monitoring for the TEA-DMMP proton bound dimer at m/z 226. Shortly after starting the data collection, the 1 µL solution of DMMP was deposited onto the filament and the filament was heated to release the vapor. The traces for these 3 experiments are presented in Figure 5.

Figure 5. Selected ion monitoring of the proton-bound heterodimer dimethyl methylphosphonate and triethylamine at m/z 226 of laboratory room air with the amine dopant remaining within the inlet. Three separate experiments were run by desorbing 1150, 115, and 11.5 µg of DMMP into the laboratory space resulting in maximum concentration of 1400, 140, and 14 pptv. The inset is an expanded view of the 14 pptv. The smooth line represents a modelled exponential decay based upon room volume and ventilation flow rates. The inset to Figure 5 is an expanded view of the lowest concentration with the line displaying the calculated exponential dilution (Equation 4). Here the concentration (C) is related to the initial concentration (C0), the ventilation rate (Q), the volume of the room (V) and the time after release (t). 13 ACS Paragon Plus Environment


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This equation can be used to calculate the concentration in an exponential dilution flask and is also used in industrial hygiene as a room purge equation. This equation was used for the modeled line in Figure 5 by assuming the instrument response correlates with the concentration in the room. The maximum signal intensity at 3 minutes was used as a substitute for C0, V was the total volume of the room, Q was the venting air flow rate from the exhaust hood and t was the time in minutes after the maximum peak height was observed.

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షೂ೟ ೇ

(4)

As seen in the inset, there is a slight deviation between the expected and measured data (Figure 5). The exponential dilution equation assumes rapid and complete mixing and the observed deviation is likely due to poor mixing throughout the room and possible losses to the various surfaces encountered by the vapor. Although the signals do not exactly overlap, the modeled data reasonably predicts the room refresh rate and when the vapor should reach background levels. This experiment demonstrates the ability for real-time monitoring of room air conditions at or below ppt levels. This method could serve to verify safe laboratory operations along with assessing proper laboratory ventilation.

Conclusions Substituted amines such as trialkylamines possess high proton affinities resulting in prominent selectivity among ambient ionization techniques. A limited propensity for trialkylamines to cluster with water or even other amines results in the formation of a single stable reagent ion. The ability of an organophosphorus compound to form a relatively strong -N-H+-O proton-bound heterodimer with the trialkylamine provides a unique ion chemistry suitable for analysis by AFT-MS. The extended ionization time provided by the AFT allows for real-time detection of OPCs at the low to sub pptv range. The sensitivity was correlated by 3 different techniques including: 1) use of reaction time, collision rate constant, and relative peak intensities, 2) estimated concentration from a permeation tube, and 3) the direct desorption of pg levels into the sample flow. The technology demonstrated real-time monitoring of a laboratory environment initially with ppt levels of vapor shown to decay exponentially over about an hour to baseline levels. The responses observed in this investigation, both relative ion intensity and the identity of the adducts formed, were repeatable over several months within our laboratory. The trace background chemical contaminants in other locations may vary and could impact ion formation and sensitivity. The Implementation of the AFT-MS for on-site analysis would benefit from the integration to a smaller mass spectrometer.

Acknowledgments The authors would like to acknowledge the Laboratory Directed Research and Development program at the Paciﬁc Northwest National Laboratory for funding this research. The Pacific Northwest


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National Laboratory is a multi-program national laboratory operated for the U.S. Department of Energy by Battelle Memorial Institute.

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(20) Eiceman, G.; Nazarov, E.; Stone, J., Chemical standards in ion mobility spectrometry. Analytica Chimica Acta 2003, 493 (2), 185-194. (21) Fernández-Maestre, R.; Harden, C. S.; Ewing, R. G.; Crawford, C. L.; Hill, H. H., Chemical standards in ion mobility spectrometry. Analyst 2010, 135 (6), 1433-1442. (22) Kaur-Atwal, G.; O’Connor, G.; Aksenov, A. A.; Bocos-Bintintan, V.; Thomas, C. P.; Creaser, C. S., Chemical standards for ion mobility spectrometry: a review. Int. J. Ion Mobil. Spec. 2009, 12 (1), 1-14. (23) Larson, J. W.; McMahon, T., Formation, thermochemistry, and relative stabilities of proton-bound dimers of oxygen n-donor bases from ion cyclotron resonance solvent-exchange equilibrium measurements. Journal of the American Chemical Society 1982, 104 (23), 6255-6261. (24) Mautner, M., The ionic hydrogen bond and ion solvation. 1. NH+.cntdot..cntdot..cntdot.O, NH+.cntdot..cntdot..cntdot.N, and OH+.cntdot..cntdot..cntdot.O bonds. Correlations with proton affinity. Deviations due to structural effects. Journal of the American Chemical Society 1984, 106 (5), 1257-1264. (25) Yamdagni, R.; Kebarle, P., Gas-phase basicities of amines. Hydrogen bonding in proton-bound amine dimers and proton-induced cyclization of. alpha.,. omega.-diamines. Journal of the American Chemical Society 1973, 95 (11), 3504-3510. (26) Meot-Ner, M.; Sieck, L. W., The Ionic Hydrogen Bond. 1. Sterically Hindered Bonds. Solvation and Clustering of Protonated Amines and Pyridines. Journal of the American Chemical Society 1983, 105 (10), 2956-2961. (27) Ewing, R.; Eiceman, G.; Harden, C.; Stone, J., The kinetics of the decompositions of the proton bound dimers of 1, 4-dimethylpyridine and dimethyl methylphosphonate from atmospheric pressure ion mobility spectra. Int J Mass Spectrom 2006, 255, 76-85.


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