Advertisement

Using differential ion mobility spectrometry to perform class-specific ion-molecule reactions of 4-quinolones with selected chemical reagents

  • Pascal Schorr
  • Dietrich A. VolmerEmail author
Communication
Part of the following topical collections:
  1. Close-Up of Current Developments in Ion Mobility Spectrometry

Abstract

Gas phase ion/molecule reactions are often used in analytical applications to support the analysis of isomers or to identify specific functional groups of organic molecules. Until now, deliberate chemical reactions have not been performed in differential ion mobility spectrometry (DMS) devices except for hydrogen exchange and cluster formation. The present work extends that of Colorado and Brodbelt (Anal Chem 66:2330–5, 1994) on ion/molecule reactions in an ion trap mass spectrometer. In this study, class-specific chemical reactions of 4-quinolone antibiotics with various chemical reagents were used to demonstrate the analytical utility of ion/molecule reactions in a DMS drift cell. For these reactions, dehydrated reactive precursor ions were initially formed and made to undergo annulation reactions with selected reagents within the timescale of the DMS separation. Careful study of the energies required for dissociation of the adducts confirmed the covalent nature of the newly formed bond; thus demonstrating the analytical utility of this approach.

Graphical abstract

Keywords

Differential ion mobility spectrometry Ion/molecule reactions 4-Quinolone antibiotics Protomer separation 

Notes

Author contributions

The manuscript was written through contributions of all authors.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

References

  1. 1.
    Kolakowski BM, Mester Z. Review of applications of high-field asymmetric waveform ion mobility spectrometry (FAIMS) and differential mobility spectrometry (DMS). Analyst. 2007;132(9):842–64.CrossRefGoogle Scholar
  2. 2.
    Varesio E, Le Blanc JCY, Hopfgartner G. Real-time 2D separation by LC × differential ion mobility hyphenated to mass spectrometry. Anal Bioanal Chem. 2012;402(8):2555–64.CrossRefGoogle Scholar
  3. 3.
    May JC, Goodwin CR, Lareau NM, Leaptrot KL, Morris CB, Kurulugama RT, et al. Conformational ordering of biomolecules in the gas phase: nitrogen collision cross sections measured on a prototype high resolution drift tube ion mobility-mass spectrometer. Anal Chem. 2014;86(4):2107–16.CrossRefGoogle Scholar
  4. 4.
    Jurneczko E, Barran PE. How useful is ion mobility mass spectrometry for structural biology? The relationship between protein crystal structures and their collision cross sections in the gas phase. Analyst. 2011;136(1):20–8.CrossRefGoogle Scholar
  5. 5.
    Mesleh MF, Hunter JM, Shvartsburg AA, Schatz GC, Jarrold MF. Structural information from ion mobility measurements: effects of the long-range potential. J Phys Chem. 1996;100(40):16082–6.CrossRefGoogle Scholar
  6. 6.
    Hall AB, Coy SL, Nazarov EG, Vouros P. Rapid separation and characterization of cocaine and cocaine cutting agents by differential mobility spectrometry-mass spectrometry. J Forensic Sci. 2012;57(3):750–6.CrossRefGoogle Scholar
  7. 7.
    Kovačević B, Schorr P, Qi Y, Volmer DA. Decay mechanisms of protonated 4-quinolone antibiotics after electrospray ionization and ion activation. J Am Soc Mass Spectrom. 2014;25(11):1974–86.CrossRefGoogle Scholar
  8. 8.
    Johnson RS, Krylov D, Walsh KA. Proton mobility within electrosprayed peptide ions. J Mass Spectrom. 1995;30(2):386–7.CrossRefGoogle Scholar
  9. 9.
    Campbell JL, Le Blanc JCY, Schneider BB. Probing electrospray ionization dynamics using differential mobility spectrometry: the curious case of 4-aminobenzoic acid. Anal Chem. 2012;84(18):7857–64.CrossRefGoogle Scholar
  10. 10.
    Schmidt J, Meyer MM, Spector I, Kass SR. Infrared multiphoton dissociation spectroscopy study of protonated p -aminobenzoic acid: does electrospray ionization afford the amino- or carboxy-protonated ion? J Phys Chem A. 2011;115(26):7625–32.CrossRefGoogle Scholar
  11. 11.
    Tian Z, Kass SR. Gas-phase versus liquid-phase structures by electrospray ionization mass spectrometry. Angew Chem Int Ed. 2009;48(7):1321–3.CrossRefGoogle Scholar
  12. 12.
    Krylova N, Krylov E, Eiceman GA, Stone JA. Effect of moisture on the field dependence of mobility for gas-phase ions of organophosphorus compounds at atmospheric pressure with field asymmetric ion mobility spectrometry. J Phys Chem A. 2003;107(19):3648–54.CrossRefGoogle Scholar
  13. 13.
    Zhu H, Max JP, Marcum CL, Luo H, Abu-Omar MM, Kenttämaa HI. Identification of the phenol functionality in deprotonated monomeric and dimeric lignin degradation products via tandem mass spectrometry based on ion–molecule reactions with diethylmethoxyborane. J Am Soc Mass Spectrom. 2016;27(11):1813–23.CrossRefGoogle Scholar
  14. 14.
    Watkins MA, Winger BE, Shea RC, Kenttämaa HI. Ion-molecule reactions for the characterization of polyols and polyol mixtures by ESI/FT-ICR mass spectrometry. Anal Chem. 2005;77(5):1385–92.CrossRefGoogle Scholar
  15. 15.
    Sheng H, Tang W, Yerabolu R, Max J, Kotha RR, Riedeman JS, et al. Identification of N-oxide and sulfoxide functionalities in protonated drug metabolites by using ion-molecule reactions followed by collisionally activated dissociation in a linear quadrupole ion trap mass spectrometer. J Organomet Chem. 2016;81(2):575–86.CrossRefGoogle Scholar
  16. 16.
    Pyatkivskyy Y, Ryzhov V. Coupling of ion-molecule reactions with liquid chromatography on a quadrupole ion trap mass spectrometer. Rapid Commun Mass Spectrom. 2008;22(8):1288–94.CrossRefGoogle Scholar
  17. 17.
    Grigorean G, Lebrilla CB. Enantiomeric analysis of pharmaceutical compounds by ion/molecule reactions. Anal Chem. 2001;73(8):1684–91.CrossRefGoogle Scholar
  18. 18.
    Trupia L, Dechamps N, Flammang R, Bouchoux G, Nguyen MT, Gerbaux P. Isomeric recognition by ion/molecule reactions: the ionized phenol-cyclohexadienone case. J Am Soc Mass Spectrom. 2008;19(1):126–37.CrossRefGoogle Scholar
  19. 19.
    Eismin RJ, Fu M, Yem S, Widjaja F, Kenttämaa HI. Identification of epoxide functionalities in protonated monofunctional analytes by using ion/molecule reactions and collision-activated dissociation in different ion trap tandem mass spectrometers. J Am Soc Mass Spectrom. 2012;23(1):12–22.CrossRefGoogle Scholar
  20. 20.
    Habicht SC, Vinueza NR, Amundson LM, Kenttämaa HI. Comparison of functional group selective ion–molecule reactions of trimethyl borate in different ion trap mass spectrometers. J Am Soc Mass Spectrom. 2011;22(3):520–30.CrossRefGoogle Scholar
  21. 21.
    Colorado A, Brodbelt J. Class-selective collisionally activated dissociation/ion-molecule reactions of 4-quinolone antibiotics. Anal Chem. 1994;66(14):2330–5.CrossRefGoogle Scholar
  22. 22.
    Rand KD, Pringle SD, Morris M, Engen JR, Brown JM. ETD in a traveling wave ion guide at tuned Z-spray ion source conditions allows for site-specific hydrogen/deuterium exchange measurements. J Am Soc Mass Spectrom. 2011;22(10):1784–93.CrossRefGoogle Scholar
  23. 23.
    Valentine SJ, Clemmer DE. H/D exchange levels of shape-resolved cytochrome c conformers in the gas phase. J Am Chem Soc. 1997;119(15):3558–66.CrossRefGoogle Scholar
  24. 24.
    Campbell JL, Yang AM-C, Melo LR, Hopkins WS. Studying gas-phase interconversion of tautomers using differential mobility spectrometry. J Am Soc Mass Spectrom. 2016;27(7):1277–84.CrossRefGoogle Scholar
  25. 25.
    Walker SWC, Mark A, Verbuyst B, Bogdanov B, Campbell JL, Hopkins WS. Characterizing the tautomers of protonated aniline using differential mobility spectrometry and mass spectrometry. J Phys Chem A. 2018;122(15):3858–65.CrossRefGoogle Scholar
  26. 26.
    Zhu S, Campbell JL, Chernushevich I, Le Blanc JCY, Wilson DJ. Differential mobility spectrometry-hydrogen deuterium exchange (DMS-HDX) as a probe of protein conformation in solution. J Am Soc Mass Spectrom. 2016;27(6):991–9.CrossRefGoogle Scholar
  27. 27.
    Purves RW, Ells B, Barnett DA, Guevremont R. Combining H-D exchange and ESI-FAIMS-MS for detecting gas-phase conformers of equine cytochrome c. Can J Chem. 2005;83(11):1961–8.CrossRefGoogle Scholar
  28. 28.
    Schneider BB, Covey TR, Coy SL, Krylov EV, Nazarov EG. Planar differential mobility spectrometer as a pre-filter for atmospheric pressure ionization mass spectrometry. Int J Mass Spectrom. 2010;298(1–3):45–54.CrossRefGoogle Scholar
  29. 29.
    Schneider BB, Covey TR, Coy SL, Krylov EV, Nazarov EG. Control of chemical effects in the separation process of a differential mobility mass spectrometer system. Eur J Mass Spectrom. 2010;16(1):57–71.CrossRefGoogle Scholar
  30. 30.
    Lapthorn C, Dines TJ, Chowdhry BZ, Perkins GL, Pullen FS. Can ion mobility mass spectrometry and density functional theory help elucidate protonation sites in “small” molecules? Rapid Commun Mass Spectrom. 2013;27(21):2399–410.CrossRefGoogle Scholar
  31. 31.
    Neta P, Godugu B, Liang Y, Simón-Manso Y, Yang X, Stein SE. Electrospray tandem quadrupole fragmentation of quinolone drugs and related ions. On the reversibility of water loss from protonated molecules. Rapid Commun Mass Spectrom. 2010;24(22):3271–8.CrossRefGoogle Scholar
  32. 32.
    Liang Y, Neta P, Simón-Manso Y, Stein SE. Reaction of arylium ions with the collision gas N 2 in electrospray ionization mass spectrometry. Rapid Commun Mass Spectrom. 2015;29(7):629–36.CrossRefGoogle Scholar
  33. 33.
    Neta P, Farahani M, Simón-Manso Y, Liang Y, Yang X, Stein SE. Unexpected peaks in tandem mass spectra due to reaction of product ions with residual water in mass spectrometer collision cells. Rapid Commun Mass Spectrom. 2014;28(23):2645–60.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Bioanalytical ChemistryHumboldt-Universität zu BerlinBerlinGermany

Personalised recommendations