Reaction-Based Azide Gas Sensing with Tailored Ionic Liquids

Technical Note pubs.acs.org/ac

Reaction-Based Azide Gas Sensing with Tailored Ionic Liquids Measured by Quartz Crystal Microbalance Ming-Chung Tseng and Yen-Ho Chu* Department of Chemistry and Biochemistry, National Chung Cheng University 168 University Road, Chiayi 62102, Taiwan, ROC S Supporting Information *

ABSTRACT: On the basis of the strain-promoted [3 + 2] cycloaddition reaction performed at ambient temperature, a labelfree, online, and chemospecific gas-phase measurement of organic azides in real time was efficiently achieved on QCM chips thin-coated with tailored ionic liquid TIL 1.

T

monitor workers with occupational exposure but also to distinguish cigarette smokers and nonsmokers.4 We were intrigued by the recent advances of click chemistry, the Huisgen 1,3-dipolar azide, alkyne [3 + 2] cycloaddition,5,6 and envisaged that, in conjunction with QCM and tailored ionic liquids, this high-yielding reaction (the strain-promoted cycloadditions,7 in particular) should allow chemoselective, rapid, and real-time detection of organic azide gases. Gas analysis by GC/MS8 or on ordered mesoporous metal oxide and silica materials9 has been exploited for commercial practices. The GC/MS method, however, requires expensive instrumentation, skilled analysis, and expert interpretation, limiting its widespread applications. Organic polymer and mixed metal oxide adsorbent arrays are often nonspecific and exhibit poor selectivity for detection of gas samples. Among many possible materials, we envisioned that ionic liquids should be promising candidates as affinity agents primarily due to their tunable chemical reactivity.1 In addition, the negligible vapor pressure of ionic liquids ensures that the sensors do not “dry out” on QCM chips and our ionic liquids can readily be used free of leakage during the measurements, making ionic liquids highly attractive for chemoselective gas sensing. Here, we demonstrate TIL 1 as the chemical reagent for chemospecific detections of organic azide gases. Due to its severe distortion from the ideal linear geometry of the triple bond on cyclooctyne fused with a cyclopropane ring that raises its ground state energy and hence lowers reaction barriers in cycloaddition reaction,7,10 the strained TIL 1 should possess

his technical note describes our development of a technique based on ionic liquids specifically tailored for online, label-free, and chemoselective detection of organic azide gases measured by quartz crystal microbalance (QCM) in real time. Ionic liquids are organic salts made to melt at low temperatures, and many of them are liquid at ambient temperature.1 Ionic liquids carry numerous desirable properties such as negligible vapor pressure, good thermal and chemical stability, and attractive recyclability that are well-suited for a range of applications, including reaction media for organic synthesis and affinity separation of biomolecules.1 Ionic liquids offer a platform of tunable structures on which the properties of both cation and anion can be independently engineered. In our research, we are interested in developing new ionic liquids and have an ongoing program to evaluate ionic liquids as novel and stable media for chemical and biochemical applications.2 Herein, we are reporting a new ionic liquid TIL 1 that gives chemoselective measurement to organic azide gases at ambient temperature (Figure 1). This TIL 1 does not require dilution and can be used directly and real-time measured by QCM without any chemical immobilization on quartz chips. Analysis of gases, such as air pollutants and volatile organic compounds (VOCs) from breath, is of fundamental importance and closely linked to environmental outcomes as well as human health.3 For example, breath benzene has been used not only to

Received: December 11, 2013 Accepted: January 24, 2014 Published: January 28, 2014

Figure 1. Structures of tailored ionic liquids TIL 1 and TIL 2. © 2014 American Chemical Society

1949

dx.doi.org/10.1021/ac404011z | Anal. Chem. 2014, 86, 1949−1952

Analytical Chemistry

Technical Note

Scheme 1. Synthesis of Tailored Ionic Liquid TIL 1

were cleaned with NaOH (2 N) for 30 min, water for 10 min, and HCl (1 N) for 5 min to remove organic absorbent impurities. Finally, quartz chips were rinsed with water thoroughly and dried under nitrogen. The flow rate of the carrier gas was controlled by a commercial Supelco flow meter (Super Chroma Enterprise Ltd., Taipei, Taiwan, ROC). Organic vapors were obtained by gasifying the chemicals in the sealed glass container (1.26 L). With the use of a commercial apparatus for QCM measurements, a rapid initial nonspecific frequency decrease (approximately 0.1 to 0.4 Hz) was typically detected within 5 s after sample injection, which was totally insignificant with reference to reaction-based frequency drops owing to TIL click reactions with azide gases. The ionic liquid solutions were prepared by dissolving TIL 1 or TIL 2 (1 μL) in acetonitrile (HPLC grade, 300 μL). These freshly prepared solutions (1 μL) were carefully pipetted onto the cleaned bare gold electrodes, at the center of quartz chip. The ionic liquid coated chips were placed in a heating oven (110 °C) for 15 s to remove residual acetonitrile. The quartz sensor chips were then mounted in the gas flow chamber (100 cm3) with nitrogen as the carrier gas at a flow rate of 3.0 mL/ min. Until a stable baseline was obtained, gaseous azide samples were injected into the chamber. The resonance frequency drops versus time curves were measured and recorded.

much greater enhancement in reactivity than the unstrained TIL 2 toward organic azides. This TIL 2 is therefore expected to be less sensitive or insensitive to azide gas detection. To the best of our knowledge, this click reaction using ionic liquids for chemoselective gas-phase detection of organic azides by QCM has not been reported in the literature.

■

EXPERIMENTAL SECTION Chemical Synthesis of Tailored Ionic Liquids. The detailed experimental procedures of tailored ionic liquids TIL 1 (Scheme 1) and TIL 2 (Scheme S1 of the Supporting Information) syntheses were given in the Supporting Information. Both TIL 1 and TIL 2 are colorless viscous liquid at ambient temperature. TIL 1. IR(KBr): 3396, 3148, 2922, 1714, 1522, 1352, 1193, 1057, 740 cm−1. 1H NMR (400 MHz, CDCl3): δ 0.66−0.70 (m, 2H, 2 × CH of exo isomer), 0.92−0.96 (m, 2H, 2 × CH of endo isomer), 1.33−1.46 (m, 2H, OH of exo isomer + CHCO of endo and exo isomers), 1.50−1.56 (m, 1H, OH of endo isomer), 2.15−2.40 (m, 6H, 3 × CH2 of exo and endo isomers), 2.85 (qn, J = 7.6 Hz, 2H, bicyclo ring CH2CH2CH2), 3.21 (t, J = 7.6 Hz, 2H, bicyclo ring CH2CH2CC), 3.55 (q, J = 5.9 Hz, 2H, CH2), 3.92 (d, J = 6.9 Hz, 2H, CH2O of exo isomer), 4.11 (d, J = 6.9 Hz, 2H, CH2O of endo isomer), 4.19 (t, J = 5.8 Hz, 2H, CH2), 4.30 (t, J = 7.3 Hz, 2H, bicyclo ring NCH2), 5.63− 5.66 (m, 1H, NH), 7.21 (d, J = 9.8 Hz, 2H, imidazole H). 13C NMR (100 MHz, CDCl3): δ 17.4, 20.0, 21.2, 21.3, 22.7, 22.8, 23.4, 25.7, 28.9, 33.1, 40.2, 42.0, 48.1, 48.9, 63.2, 69.4, 98.6, 98.7, 117.6, 119.6 (q, JCF = 319 Hz, CF3), 119.7, 126.2, 152.5, 157.2. FAB-HRMS: m/z [M]+ calcd for C19H20N3O2 328.2025; found, 328.2026. TIL 2. IR (KBr): 3265, 3149, 2986, 2136, 1584, 1357, 1192, 1059, 740, 656 cm−1. 1H NMR (400 MHz, DMSO-d6): δ 2.67 (qn, J = 7.7 Hz, 2H), 3.15 (t, J = 7.7 Hz, 2H), 3.71 (t, J = 2.5 Hz, 1H), 4.19 (t, J = 7.3 Hz, 2H), 5.06 (d, J = 2.3 Hz, 2 H), 7.60 (d, J = 2.0 Hz, 1H), 7.61 (d, J = 2.0 Hz, 1H). 13C NMR (100 MHz, DMSO-d6): δ 23.3, 26.0, 38.2, 48.5, 76.1, 79.1, 118.6, 179.1 (q, JCF = 320 Hz, CF3), 125.9, 153.1. FAB-HRMS: m/z [M]+ calcd for C9H11N2 147.0922, found 147.0922. QCM Measuremts. The PSS QCM system (9 MHz) available from the ANT Technology Company (Taipei, Taiwan, ROC) (http://www.anttech.com.tw/) was operated under room temperature and using nitrogen as carrier gas. The 9 MHz AT-cut quartz chips deposited with gold electrodes (area 11 mm2) on both sides were commercially available (ANT Technology Company). The gold electrodes on chips

■

RESULTS AND DISCUSSION

Scheme 1 illustrates our synthesis of TIL 1 of which its affinity element 6, bicyclo[6.1.0]nonyne (BCN), was assembled from inexpensive 1,5-cyclooctadiene 3 and ethyl diazoacetate following a modified procedure previously developed by van Delft and co-workers.11 The highly reactive biarylazacyclooctynone (BARAC) and other aza-dibenzocyclooctynes were not selected in this study because of their large molecular weights (likely resulting in TILs as solid salts at ambient temperature) and, most significantly, their reported chemical instability, limiting its practical applicability.12 In our hands, the overall isolated yield of TIL 1 (endo/exo = 1:2) synthesis was 23% in six steps (see the Supporting Information). The TIL 2 could readily be afforded with high isolated yield (71%) in two steps from reaction of propagyl bromide with 6,7-dihydro-5Hpyrrolo[1,2-a]imidazole previously prepared in our laboratory (Scheme S1 of the Supporting Information).13 Both TIL 1 and TIL 2 are colorless liquid at ambient temperature. Results in Figure 2 unambiguously show that, having the same concentration (660 ppb) for all gases tested, the TIL 1 thin-coated on QCM chip only reacted chemoselectively with 1950

dx.doi.org/10.1021/ac404011z | Anal. Chem. 2014, 86, 1949−1952

Analytical Chemistry

Technical Note

Figure 3. Chemoselective detection of aliphatic azides (allyl azide, butyl azide, propyl azide, and pentyl azide) and an aryl azide (phenyl azide) gases (146 ppb each) by 9 MHz QCM thin-coated with TIL 1 (3.3 nL each, 300 nm thickness). The QCM response of benzyl azide gas (146 ppb) reaction with TIL 2 (3.3 nL, 300 nm thickness) coated on QCM chip was also displayed and vertically shifted by 20 Hz.

Figure 2. Chemoselective detection of butyl azide, acetone, methanol, ethyl acetate, hexane, and water gases (660 ppb each) all by 9 MHz QCM thin-coated with TIL 1 (3.3 nL, 300 nm thickness). The QCM response curves for acetone, methanol, ethyl acetate, hexane, and water gases were vertically shifted (20 Hz in between) for clarity. The QCM response of butyl azide gas (660 ppb) reaction with TIL 2 (3.3 nL, 300 nm thickness) coated on the QCM chip was also displayed and vertically shifted by 120 Hz. Nitrogen was used as the carrier gas, and gaseous samples were injected at 750 s. The resonance frequency drop, ΔF, is the QCM response on the quartz chip surface.

Figure 4 further provides detailed quantitative studies of TIL 1 reactions with benzyl and butyl azide gases (QCM sensorgrams

butyl azide gas.14,15 Much to our satisfaction, this IL-on-chip system was totally insensitive to common VOCs such as acetone, methanol, ethyl acetate, hexane, and most significantly, moisture (ΔF ∼ 0 Hz); that is, any water present in the gas stream would not be in any direct competition with azides. It is also noted that the irreversible nature of the frequency drops from QCM measurements of butyl azide sensing by TIL 1 indicated its nonequilibrium and permanent formation of the triazole product, confirming the excellent reactivity of TIL 1 toward azide gases. The EI-HRMS analysis further supported the formation of the triazole adduct of TIL 1 reaction with butyl azide gas on sensorchip: a new, correct mass of 427.2821 for [C23H35N6O2]+ ion was experimentally obtained (see the Supporting Information). Furthermore, this TIL 1 greatly outperformed TIL 2 upon capturing butyl azide gas (ΔF = −209 Hz for TIL 1 vs ΔF = −0.3 Hz for TIL 2) (Figure 2),16 proving that TIL 2 was totally inert to butyl azide gas during the entire reaction time and the irreversible frequency drop in the continuous flow QCM measurement was not due to the nonspecific dissolution of azide gas in IL 1. The results in Figure 2 clearly demonstrate that TIL 1 is chemically specific and highly reactive toward capturing azide gases, suggesting that TIL 1 is sensitive and well-suited for organic azide sensing. As we were encouraged by the result of butyl azide gas analysis using QCM, we next turned our attention to the TIL 1 detection of other azide gases and investigated TIL 1 to test its general effectiveness as a label-free azide gas sensor. Six organic azide gases were examined, and Figure 3 shows the QCM results. We were pleased that our IL-on-chip system shows high sensitivity toward detection of both aliphatic and aryl azide gases. Among all azide gases (146 ppb each) investigated, benzyl azide produced the largest QCM response (ΔF = −319 Hz), which is consistent with its reported lower activation energy than that of, for example, allyl azide (Figure 3).16b Interestingly, our TIL 1 elicits a similar range of QCM responses when exposed to small aliphatic azide gases (ΔF = −11 ∼ −32 Hz). Aryl azide gas such as phenyl azide produced large ΔF value (−88 Hz) upon being captured by TIL 1 (Figure 3). The unstrained TIL 2 was totally inert toward benzyl azide sensing. Our IL-on-chip system has shown excellent sensitivity toward chemospecific detection of azide gases (Figures 2 and 3).

Figure 4. Detection sensitivity plot of ΔF (Hz) vs concentration (ppb) of benzyl and butyl azide gases using a 9 MHz QCM thincoated with TIL 1 (blue) and TIL 2 (red).

in Figure S1 of the Supporting Information). Both gases showed essentially linear QCM frequency responses within the range of concentrations tested. In our hands, this strainpromoted TIL 1 platform is highly selective to azide gases: at ΔF = −10 Hz, the sensitivity of detection was 5 ppb for benzyl azide and 35 ppb for butyl azide, respectively (Figure 4); that is, an approximately 7-fold higher sensitivity in detection of benzyl azide than that of butyl azide was evident. Furthermore, TIL 2 was totally insensitive to both azide gases (Figure 4). The aforementioned QCM results further prompted us to initiate a preliminary investigation on detection of gases having dual functional groups such as 2-azioethyl amine. The result is given in Figure 5. To our delight, TIL 1 showed chemoselectivity to 2-azioethyl amine gas (536 ppb) and the amino triazole adduct formed on chip then readily captured an aldehyde gas valeraldehyde, 536 ppb) by a nonequilibrium Schiff-base-forming reaction.2e This preliminary result revealed that TIL 1 is highly chemoselective and itself is inert to aldehyde gas (Figure 5). Since the BCN in TIL 1 carries a reactive alkyne dienophile group, we envisioned that our IL-on-chip system should also allow chemical sensing of conjugated diene gases such as cyclopentadiene through the Diels−Alder [4 + 2] cycloaddition reaction. Figure S2 of the Supporting Information illustrated that TIL 1 readily captured cyclopentadiene gas at low ppb at ambient temperature (see the Supporting Information).17 TIL 2 was, again, totally insensitive to cyclopentadiene under our 1951

dx.doi.org/10.1021/ac404011z | Anal. Chem. 2014, 86, 1949−1952

Analytical Chemistry

Technical Note

Chang, C. I.; Chu, Y.-H. Curr. Org. Synth. 2012, 9, 74−95. (c) Giernoth, R. Angew. Chem., Int. Ed. 2010, 49, 2834−2839. (d) Huo, C.; Chan, T. H. Chem. Soc. Rev. 2010, 39, 2977−3006. (e) Coleman, D.; Gathergood, N. Chem. Soc. Rev. 2010, 39, 600−637. (f) Sowmiah, S.; Srinivasadesikan, V.; Tseng, M.-C.; Chu, Y.-H. Molecules 2009, 14, 3780−3813. (g) Plechkova, N. V.; Seddon, K. R. Chem. Soc. Rev. 2008, 37, 123−150. (2) (a) Liu, Y.-L.; Tseng, M.-C.; Chu, Y.-H. Chem. Commun. 2013, 49, 2560−2562. (b) Shi, Y.; Liu, Y.-L.; Lai, P.-Y.; Tseng, M.-C.; Tseng, M.-J.; Li, Y.; Chu, Y.-H. Chem. Commun. 2012, 48, 5325−5327. (c) Tseng, M.-C.; Cheng, H.-T.; Shen, M.-J.; Chu, Y.-H. Org. Lett. 2011, 13, 4434−4437. (d) Chen, C.-W.; Tseng, M.-C.; Hsiao, S.-K.; Chen, W.-H.; Chu, Y.-H. Org. Biomol. Chem. 2011, 9, 4188−4193. (e) Tseng, M.-C.; Chu, Y.-H. Chem. Commun. 2010, 46, 2983−2985. (f) Tseng, M.-C.; Tseng, M.-J.; Chu, Y.-H. Chem. Commun. 2009, 7503−7505. (3) Amann, A.; Corradi, M.; Mazzone, P.; Mutti, A. Expert Rev. Mol. Diagn. 2011, 11, 207−217. (4) (a) Jia, C.; Yu, X.; Masiak, W. Sci. Total Environ. 2012, 419, 225− 232. (b) Brugnone, F.; Perbellini, L.; Faccini, G. B.; Pasini, F.; Danzi, B.; Maranelli, G.; Romeo, L.; Gobbi, M.; Zedde, A. Am. J. Ind. Med. 1989, 16, 385−399. (5) For a recent review on organic azides, see: Brase, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew. Chem., Int. Ed. 2005, 44, 5188− 5240. (6) For a most recent review on click chemistry, see: Thirumurugan, P.; Matosiuk, D.; Jozwiak, K. Chem. Rev. 2013, 113, 4905−4979. (7) Debets, M. F.; Van Berkel, S. S.; Dommerholt, J.; Dirks, A. J.; Rutjes, F. P. J. T.; van Delft, F. L. Acc. Chem. Res. 2011, 44, 805−815. (8) Lai, H.; Leung, A.; Magee, M.; Almirall, J. R. Anal. Bioanal. Chem. 2010, 396, 2997−3007. (9) Wagner, T.; Haffer, S.; Weinberger, C.; Klaus, D.; Tiemann, M. Chem. Soc. Rev. 2013, 42, 4036−4053. (10) Hber, D.; Rosner, P.; Tochtermann, W. Eur. J. Org. Chem. 2005, 4231−4247. (11) Dommerholt, J.; Schmidt, S.; Temming, R.; Hendriks, L. J. A.; Rutjes, F. P. J. T.; van Hest, J. C. M.; Lefeber, D. J.; Friedl, P.; van Delft, F. L. Angew. Chem., Int. Ed. 2010, 49, 9422−9425. (12) Unwanted side reactions from BARAC, including intramolecular cyclization, aza-Claisen rearrangement and Ritter reaction, have been reported: (a) Chigrinova, M.; McKay, C. S.; Beaulieu, L.-P. B.; Udachin, K. A.; Beauchemin, A. M.; Pezacki, J. P. Org. Biomol. Chem. 2013, 11, 3426−3436. (b) Debets, M. F.; van Berkel, S. S.; Schoffelen, S.; Rutjes, F. P. J. T.; van Hest, J. C. M.; van Delft, F. L. Chem. Commun. 2010, 46, 97−99. (13) Kan, H.-C.; Tseng, M.-C.; Chu, Y.-H. Tetrahedron 2007, 63, 1644−1653. (14) For a recent review on QCM, see Cheng, C. I.; Chang, Y.-P.; Chu, Y.-H. Chem. Soc. Rev. 2012, 41, 1947−1971. (15) A commercial 9 MHz QCM gas sensing device PSS from ANT Technology (www.anttech.com.tw) was employed in this study. (16) The enhanced reactivity in the cycloaddition of cyclooctyne in TIL 1, as compared to a linear, unstrained terminal alkyne such as TIL 2, likely derives either from the ring-strain energy (18 kcal/mol)16a present in cyclooctyne or from the low activation energy (6.5 kcal/ mol)16b of BCN cyclooctyne: (a) Agard, N. J.; Prescher, J. A.; Bertozzi, C. R. J. Am. Chem. Soc. 2004, 126, 15046−15047. (b) Garcia-Hartjes, J.; Dommerholt, J.; Wennekes, T.; van Delft, F. L.; Zuilhof, H. Eur. J. Org. Chem. 2013, 3712−3720. (17) ESI-HRMS analysis demonstrated the formation of the Diels− Alder adduct of TIL 1 reaction with cyclopentadiene gas: a correct mass of 394.2500 for [C24H32N3O2]+ ion (calcd mass, 394.2495) was experimentally obtained (see the Supporting Information).

Figure 5. Chemoselective detection of 2-azidoethyl amine gas (536 ppb) by 9 MHz QCM thin-coated with TIL 1. Gas samples of 2azidoethyl amine and valeraldehyde (536 ppb) were injected at 500 and 5000 s, respectively. The QCM response of two injections of valeraldehyde gas was also displayed and vertically shifted by 100 Hz for clarity.

experimental conditions (Figure S2 of the Supporting Information).

■

CONCLUSION In conclusion, we demonstrated here a successful development of tailored ionic liquids on QCM chips for online and chemoselective measurements of organic azide gases in real time. Our approach is cost-effective (3.3 nL per quartz chip) as the QCM chip is readily regenerated by washing away the used IL and replacing the new one (see Supporting Information). This reaction-based platform is label-free and chemoselective with fast gas diffusion into ionic liquids, applicable to small molecule gases and, most significantly, insensitive to moisture. To our knowledge, this is the first report in literature based upon cycloaddition reactions demonstrating sensitive azide and diene gases sensing in ionic liquids measured by QCM. It is also first that gas samples with dual functionalities could be studied sequentially by QCM.

■

ASSOCIATED CONTENT

S Supporting Information *

Figures S1 and S2 and Scheme S1; synthetic procedures, QCM measurements, 1H and 13C NMR spectra and data of TIL 1, TIL 2, and all azides studied. This material is available free of charge via the Internet at http://pubs.acs.org.

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Tel: (+886) 5 2428148. Fax: (+886) 5 2721040. Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS We gratefully acknowledge support of this work by grants from the National Science Council of Taiwan, ROC (NSC100-2113M-194-003-MY3, NSC101-2811-M-194-028, NSC101-3114-C194-001-ES, and NSC102-2811-M-194-023). We also thank reviewers for their constructive comments and suggestions.

■

REFERENCES

(1) For recent reviews on ionic liquids, see: (a) Tang, S.; Baker, G. A.; Zhao, H. Chem. Soc. Rev. 2012, 41, 4030−4066. (b) Sowmiah, S.; 1952

dx.doi.org/10.1021/ac404011z | Anal. Chem. 2014, 86, 1949−1952