Advertisement

A Mechanistic Study of Protonated Aniline to Protonated Phenol Substitution Considering Tautomerization by Ion Mobility Mass Spectrometry and Tandem Mass Spectrometry

  • Christopher KuneEmail author
  • Cédric Delvaux
  • Jean R. N. Haler
  • Loïc Quinton
  • Gauthier Eppe
  • Edwin De Pauw
  • Johann Far
Research Article

Abstract

We report the use of ion mobility mass spectrometry (IMMS) and energy-resolved collisional activation to investigate gas-phase reactions of protonated aniline and protonated phenol. Protonated aniline prototropic tautomerization and nucleophilic substitution (SN1) to produce phenol with traces of water in the IMMS cell are reported. Tautomerization of protonated phenol and its ability to form protonated aniline in presence of ammonia in the gas phase are also observed. These results are supported by energy landscapes obtained from computational chemistry. These structure modifications in the IMMS cell affected the measured collision cross section (CCS). A thorough understanding of the gas-phase reactions occurring in IMMS appears mandatory before using the experimental CCS as a robust descriptor which is stated by the recent literature.

Keywords

Ion mobility Mass spectrometry Tautomerism Nucleophilic substitution Aniline Phenol Gas-phase reaction Computational chemistry 

Supplementary material

13361_2019_2321_MOESM1_ESM.docx (192 kb)
ESM 1 (DOCX 192 kb)

References

  1. 1.
    Causon, T.J., Hann, S.: Theoretical evaluation of peak capacity improvements by use of liquid chromatography combined with drift tube ion mobility-mass spectrometry. J. Chromatogr. A. 1416, 47–56 (2015)CrossRefGoogle Scholar
  2. 2.
    Rainville, P.D., Wilson, I.D., Nicholson, J.K., Isaac, G., Mullin, L., Langridge, J.I., Plumb, R.S.: Ion mobility spectrometry combined with ultra performance liquid chromatography/mass spectrometry for metabolic phenotyping of urine: effects of column length, gradient duration and ion mobility spectrometry on metabolite detection. Anal. Chim. Acta. 982, 1–8 (2017)CrossRefGoogle Scholar
  3. 3.
    Chalet, C., Hollebrands, B., Janssen, H.-G., Augustijns, P., Duchateau, G.: Identification of phase-II metabolites of flavonoids by liquid chromatography–ion-mobility spectrometry–mass spectrometry. Anal. Bioanal. Chem. 410, 471–482 (2018)CrossRefGoogle Scholar
  4. 4.
    Goscinny, S., Joly, L., De Pauw, E., Hanot, V., Eppe, G.: Travelling-wave ion mobility time-of-flight mass spectrometry as an alternative strategy for screening of multi-class pesticides in fruits and vegetables. J. Chromatogr. A. 1405, 85–93 (2015)CrossRefGoogle Scholar
  5. 5.
    Goscinny, S., McCullagh, M., Far, J., De Pauw, E., Eppe, G.: Towards the use of ion mobility mass spectrometry derived collision cross section as a screening approach for unambiguous identification of targeted pesticides in food. Rapid Commun. Mass Spectrom. 0, (2019).  https://doi.org/10.1002/rcm.8395
  6. 6.
    Regueiro, J., Negreira, N., Berntssen, M.H.G.: Ion-mobility-derived collision cross section as an additional identification point for multiresidue screening of pesticides in fish feed. Anal. Chem. 88, 11169–11177 (2016)CrossRefGoogle Scholar
  7. 7.
    Kune, C., Far, J., De Pauw, E.: Accurate drift time determination by traveling wave ion mobility spectrometry: the concept of the diffusion calibration. Anal. Chem. 88, 11639–11646 (2016)CrossRefGoogle Scholar
  8. 8.
    Poyer, S., Comby-Zerbino, C., Choi, C.M., Macaleese, L., Deo, C., Bogliotti, N., Xie, J., Salpin, J.-Y., Dugourd, P., Chirot, F.: Conformational dynamics in ion mobility data. Anal. Chem. 89, 4230–4237 (2017)CrossRefGoogle Scholar
  9. 9.
    Gabelica, V., Shvartsburg, A.A., Afonso, C., Barran, P., Benesch, J.L.P., Bleiholder, C., Bowers, M.T., Bilbao, A., Bush, M.F., Campbell, J.L., Campuzano, I.D.G., Causon, T., Clowers, B.H., Creaser, C.S., De Pauw, E., Far, J., Fernandez-Lima, F., Fjeldsted, J.C., Giles, K., Groessl, M., Hogan Jr., C.J., Hann, S., Kim, H.I., Kurulugama, R.T., May, J.C., McLean, J.A., Pagel, K., Richardson, K., Ridgeway, M.E., Rosu, F., Sobott, F., Thalassinos, K., Valentine, S.J., Wyttenbach, T.: Recommendations for reporting ion mobility mass spectrometry measurements. Mass Spectrom. Rev. 0, (2019).  https://doi.org/10.1002/mas.21585
  10. 10.
    Marchand, A., Livet, S., Rosu, F., Gabelica, V.: Drift tube ion mobility: how to reconstruct collision cross section distributions from arrival time distributions? Anal. Chem. 89, 12674–12681 (2017)CrossRefGoogle Scholar
  11. 11.
    Muller, P.: Glossary of terms used in physical organic chemistry: (IUPAC Recommendations 1994). Pure Appl. Chem. 66, 1077–1184 (1994)CrossRefGoogle Scholar
  12. 12.
    Chetverin, A.B.: Evidence for a diprotomeric structure of Na,K-ATPase. Accurate determination of protein concentration and quantitative end-group analysis. FEBS Lett. 196, 121–125 (1986)CrossRefGoogle Scholar
  13. 13.
    Wood, K.V., Cooks, R.G., Burinsky, D.J., Cameron, D.: Site of gas-phase cation attachment. Protonation, methylation, and ethylation of aniline, phenol, and thiophenol. J. Organomet. Chem. 48, 5236–5242 (1983)CrossRefGoogle Scholar
  14. 14.
    Karpas, Z., Berant, Z., Stimac, R.M.: An ion mobility spectrometry/mass spectrometry (IMS/MS) study of the site of protonation in anilines. Struct. Chem. 1, 201–204 (1990)CrossRefGoogle Scholar
  15. 15.
    Smith, R.L., Chyall, L.J., Beasley, B.J., Kenttämaa, H.I.: The site of protonation of aniline. J. Am. Chem. Soc. 117, 7971–7973 (1995)CrossRefGoogle Scholar
  16. 16.
    Russo, N., Toscano, M., Grand, A., Mineva, T.: Proton affinity and protonation sites of aniline. Energetic behavior and density functional reactivity indices. J. Phys. Chem. A. 104, 4017–4021 (2000)CrossRefGoogle Scholar
  17. 17.
    Daniel Boese, A., Martin, J.M.L., De Proft, F., Geerlings, P.: The protonation site of aniline revisited: a “torture test” for electron correlation methods. ACS Symp. Ser. 958, 183–192 (2007)CrossRefGoogle Scholar
  18. 18.
    Lalli, P.M., Iglesias, B.A., Toma, H.E., De Sa, G.F., Daroda, R.J., Silva Filho, J.C., Szulejko, J.E., Araki, K., Eberlin, M.N.: Protomers: formation, separation and characterization via travelling wave ion mobility mass spectrometry. J. Mass Spectrom. 47, 712–719 (2012)CrossRefGoogle Scholar
  19. 19.
    Attygalle, A.B., Xia, H., Pavlov, J.: Influence of ionization source conditions on the gas-phase protomer distribution of anilinium and related cations. J. Am. Soc. Mass Spectrom. 28, 1575–1586 (2017)CrossRefGoogle Scholar
  20. 20.
    Boschmans, J., Jacobs, S., Williams, J.P., Palmer, M., Richardson, K., Giles, K., Lapthorn, C., Herrebout, W.A., Lemière, F., Sobott, F.: Combining density functional theory (DFT) and collision cross-section (CCS) calculations to analyze the gas-phase behaviour of small molecules and their protonation site isomers. Analyst. 141, 4044–4054 (2016)CrossRefGoogle Scholar
  21. 21.
    Van Lau, K., Kebarle, P.: Substituent effects on the intrinsic basicity of benzene: proton affinities of substituted benzenes. J. Am. Chem. Soc. 98, 7452–7453 (1976)CrossRefGoogle Scholar
  22. 22.
    DeFrees, D.J., Mclver, R.T., Hehre, W.J.: The proton affinities of phenol. J. Am. Chem. Soc. 99, 3853–3854 (1977)CrossRefGoogle Scholar
  23. 23.
    Tishchenko, O., Pham-Tran, N.-N., Kryachko, E.S., Nguyen, M.T.: Protonation of gaseous halogenated phenols and anisoles and its interpretation using DFT-based local reactivity indices. J. Phys. Chem. A. 105, 8709–8717 (2001)CrossRefGoogle Scholar
  24. 24.
    Campbell, J.L., Yang, A.M.-C., Melo, L.R., Hopkins, W.S.: Studying gas-phase interconversion of tautomers using differential mobility spectrometry. J. Am. Soc. Mass Spectrom. 27, 1277–1284 (2016)CrossRefGoogle Scholar
  25. 25.
    Ranasinghe, Y.A., Glish, G.L.: Reactions of the phenylium cation with small oxygen- and nitrogen-containing molecules. J. Am. Soc. Mass Spectrom. 7, 473–481 (1996)CrossRefGoogle Scholar
  26. 26.
    Giles, K., Pringle, S.D., Worthington, K.R., Little, D., Wildgoose, J.L., Bateman, R.H.: Applications of a travelling wave-based radio-frequency-only stacked ring ion guide. Rapid Commun. Mass Spectrom. 18, 2401–2414 (2004)CrossRefGoogle Scholar
  27. 27.
    Beegle, L.W., Kanik, I., Matz, L., Hill Jr., H.H.: Effects of drift-gas polarizability on glycine peptides in ion mobility spectrometry. Int. J. Mass Spectrom. 216, 257–268 (2002)CrossRefGoogle Scholar
  28. 28.
    Warnke, S., Seo, J., Boschmans, J., Sobott, F., Scrivens, J.H., Bleiholder, C., Bowers, M.T., Gewinner, S., Schöllkopf, W., Pagel, K., Von Helden, G.: Protomers of benzocaine: solvent and permittivity dependence. J. Am. Chem. Soc. 137, 4236–4242 (2015)CrossRefGoogle Scholar
  29. 29.
    Frisch, M., Trucks, G., Schlegel, H., Scuseria, G., Robb, M., Cheeseman, J., Scalmani, G., Barone, V., Mennucci, B., Petersson, G., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H., Izmaylov, A., Bloino, J., Zheng, G., Sonnenberg, J., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Montgomery, J., Peralta, J., Ogliaro, F., Bearpark, M., Heyd, J., Brothers, E., Kudin, K., Staroverov, V., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A., Burant, J., Iyengar, S., Tomasi, J., Cossi, M., Rega, N., Millam, J., Klene, M., Knox, J., Cross, J., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R., Yazyev, O., Austin, A., Cammi, R., Pomelli, C., Ochterski, J., Martin, R., Morokuma, K., Zakrzewski, V., Voth, G., Salvador, P., Dannenberg, J., Dapprich, S., Farkas, D.A., Foresman, J., Ortiz, J., Cioslowski, J., Fox, D.: Gaussian 09, Revision B.01. Gaussian 09 Revis. D01. Gaussian Inc, Wallingford (2009)Google Scholar
  30. 30.
    Peng, L., Hua, L., Wang, W., Zhou, Q., Li, H.: On-site rapid detection of trace non-volatile inorganic explosives by stand-alone ion mobility spectrometry via acid-enhanced evaporization. Sci. Rep. 4, 6631 (2014)CrossRefGoogle Scholar
  31. 31.
    Yanai, T., Tew, D., Handy, N.: A new hybrid exchange-correlation functional using the Coulomb-attenuating method (CAM-B3LYP). Chem. Phys. Lett. 393, 51–57 (2004)CrossRefGoogle Scholar
  32. 32.
    Larriba, C., Hogan, C.J.: Free molecular collision cross section calculation methods for nanoparticles and complex ions with energy accommodation. J. Comput. Phys. 251, 344–336 (2013)CrossRefGoogle Scholar
  33. 33.
    Larriba, C., Hogan, C.J.: Ion mobilities in diatomic gases: measurement versus prediction with non-specular scattering models. J. Phys. Chem. A. 117, 3887–3901 (2013)CrossRefGoogle Scholar
  34. 34.
    Shrivastav, V., Nahin, M., Hogan, C.J., Larriba-Andaluz, C.: Benchmark comparison for a multi-processing ion mobility calculator in the free molecular regime. J. Am. Soc. Mass Spectrom. 28, 1540–1551 (2017)CrossRefGoogle Scholar
  35. 35.
    Mesleh, M.F., Hunter, J.M., Shvartsburg, A.A., Schatz, G.C., Jarrold, M.F.: Structural information from ion mobility measurements: effects of the long-range potential. J. Phys. Chem. 100, 16082–16086 (1996)CrossRefGoogle Scholar
  36. 36.
    Wyttenbach, T., von Helden, G., Batka, J.J., Carlat, D., Bowers, M.T.: Effect of the long-range potential on ion mobility measurements. J. Am. Soc. Mass Spectrom. 8, 275–282 (1997)CrossRefGoogle Scholar
  37. 37.
    Wu, T., Derrick, J., Nahin, M., Chen, X., Larriba-Andaluz, C.: Optimization of long range potential interaction parameters in ion mobility spectrometry. J. Chem. Phys. 148, 074102 (2018)CrossRefGoogle Scholar
  38. 38.
    Kune, C., Haler, J.R.N., Far, J., De Pauw, E.: Effectiveness and limitations of computational chemistry and mass spectrometry in the rational design of target-specific shift reagents for ion mobility spectrometry. ChemPhysChem. 19, 2921–2930 (2018)CrossRefGoogle Scholar
  39. 39.
    Begala, M.: Conversion of benzoic acid into phenol in an ITMS under CI-MSn conditions. Recognition of ortho-chlorobenzoyl derivatives. J. Mass Spectrom. 53, 30–38 (2018)CrossRefGoogle Scholar
  40. 40.
    Purwaha, P., Silva, L.P., Hawke, D.H., Weinstein, J.N., Lorenzi, P.L.: An artifact in LC-MS/MS measurement of glutamine and glutamic acid: in-source cyclization to pyroglutamic acid. Anal. Chem. 86, 5633–5637 (2014)CrossRefGoogle Scholar
  41. 41.
    Paizs, B., Suhai, S.: Fragmentation pathways of protonated peptides. Mass Spectrom. Rev. 24, 508–548 (2005)CrossRefGoogle Scholar
  42. 42.
    Xia, H., Attygalle, A.B.: Transformation of the gas-phase favored O-protomer of p-aminobenzoic acid to its unfavored N-protomer by ion activation in the presence of water vapor: an ion-mobility mass spectrometry study. J. Mass Spectrom. 53, 353–360 (2018)CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2019

Authors and Affiliations

  1. 1.MOLSYS, Mass Spectrometry LaboratoryUniversity of LiègeLiègeBelgium
  2. 2.Department of Chemistry and BiochemistryFlorida International UniversityMiamiUSA

Personalised recommendations