Advertisement

Analytical and Bioanalytical Chemistry

, Volume 405, Issue 17, pp 5817–5824 | Cite as

In situ NMR spectroelectrochemistry for the structure elucidation of unstable intermediate metabolites

  • Ugo Bussy
  • Patrick Giraudeau
  • Virginie Silvestre
  • Titouan Jaunet-Lahary
  • Véronique Ferchaud-Roucher
  • Michel Krempf
  • Serge Akoka
  • Illa Tea
  • Mohammed BoujtitaEmail author
Research Paper

Abstract

In situ NMR spectroelectrochemistry is presented in this study as a useful hybrid technique for the chemical structure elucidation of unstable intermediate species. An experimental setting was designed to follow the reaction in real time during the experimental electrochemical process. The analysis of 1H NMR spectra recorded in situ permitted us (1) to elucidate the reaction pathway of the electrochemical oxidation of phenacetin and (2) to reveal the quinone imine as a reactive intermediate species without using any trapping reaction. Phenacetin has been considered as hepatotoxic at high therapeutic amounts, which is why it was chosen as a model to prove the applicability of the analytical method. The use of 1D and 2D NMR experiments led to the elucidation of the major species produced from the oxidation process. We demonstrated that in situ NMR spectroelectrochemistry constitutes a fast way for monitoring unstable quinone imines and elucidating their chemical structures.

Figure

In situ NMR spectroelectrochemistry for drug metabolism studies

Keywords

In situ NMR spectroelectrochemistry Phenacetin O-cleavage Quinone imine 

Notes

Acknowledgments

The authors thank CNRS, the University of Nantes, and the French Ministry of Higher Education and Research for financial support.

Supplementary material

216_2013_6977_MOESM1_ESM.pdf (231 kb)
ESM 1 (PDF 230 kb)

References

  1. 1.
    Richards JA, Evans DH (1975) Anal Chem 47(6):964–966CrossRefGoogle Scholar
  2. 2.
    Mincey DW, Popovich MJ, Faustino PJ, Hurst MM, Caruso JA (1990) Anal Chem 62(11):1197–1200CrossRefGoogle Scholar
  3. 3.
    Webster RD (2004) Anal Chem 76(6):1603–1610CrossRefGoogle Scholar
  4. 4.
    Sandifer ME, Zhao M, Kim S, Scherson DA (1993) Anal Chem 65:2093–2095CrossRefGoogle Scholar
  5. 5.
    Zhang X, Zwanziger JW (2011) J Magn Reson 208(1):136–147CrossRefGoogle Scholar
  6. 6.
    Klod S, Ziegs F, Dunsch L (2009) Anal Chem 81(24):10262–10267CrossRefGoogle Scholar
  7. 7.
    Albert K, Dreher E-L, Straub H, Rieker A (1987) Magn Reson Chem 25(10):919–922CrossRefGoogle Scholar
  8. 8.
    Klod S, Dunsch L (2011) Magn Reson Chem 49(11):725–729CrossRefGoogle Scholar
  9. 9.
    Klod S, Haubner K, Jaehne E, Dunsch L (2010) Chem Sci 1:743–750CrossRefGoogle Scholar
  10. 10.
    Jahn S, Karst U (2012) J Chromatogr A 1259:16–49CrossRefGoogle Scholar
  11. 11.
    Madsen KG, Olsen J, Skonberg C, Hansen SH, Jurva U (2007) Chem Res Toxicol 20(5):821–831CrossRefGoogle Scholar
  12. 12.
    Simon H, Melles D, Jacquoilleot S, Sanderson P, Zazzeroni R, Karst U (2012) Anal Chem 84(20):8777–8782CrossRefGoogle Scholar
  13. 13.
    James LP, Mayeux PR, Hinson JA (2003) Drug Metab Dispos 31(12):1499–1506CrossRefGoogle Scholar
  14. 14.
    Nouri-Nigjeh E, Bischoff R, Bruins AP, Permentier HP (2011) Analyst 136(23):5064–5067CrossRefGoogle Scholar
  15. 15.
    Yin H, Meng X, Xu Z, Chen L, Ai S (2012) Anal Methods 4(5):1445–1451CrossRefGoogle Scholar
  16. 16.
    Rodriguez S, Santos A, Romero A, Vicente F (2012) Chem Eng J 213:225–234CrossRefGoogle Scholar
  17. 17.
    Guengerich FP (2001) Chem Res Toxicol 14(6):611–650CrossRefGoogle Scholar
  18. 18.
    Prenzler PD, Bramley R, Downing SR, Heath GA (2000) Electrochem Commun 2(7):516–521CrossRefGoogle Scholar
  19. 19.
    Bussy U, Tea I, Ferchaud-Roucher V, Krempf M, Silvestre V, Galland N, Jacquemin D, Andresen-Bergström M, Jurva U, Boujtita M (2013) Anal Chim Acta 762:39–46CrossRefGoogle Scholar
  20. 20.
    Nematollahi D, Shayani-Jam H, Alimoradi M, Niroomand S (2009) Electrochim Acta 54(28):7407–7415CrossRefGoogle Scholar
  21. 21.
    Bussy U, Ferchaud-Roucher V, Tea I, Krempf M, Silvestre V, Boujtita M (2012) Electrochim Acta 69:351–357CrossRefGoogle Scholar
  22. 22.
    Novak M, Pelecanou M, Pollack L (1986) J Am Chem Soc 108:112–120CrossRefGoogle Scholar
  23. 23.
    Frydman L, Scherf T, Lupulescu A (2002) Proc Natl Acad Sci USA 99:15858–15862CrossRefGoogle Scholar
  24. 24.
    Giraudeau P, Shrot Y, Frydman L (2009) J Am Chem Soc 131:13902–13903CrossRefGoogle Scholar
  25. 25.
    Queiroz LHK Jr, Queiroz DPK, Dhooghe L, Ferreira AG, Giraudeau P (2012) Analyst 137:2357–2361CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Ugo Bussy
    • 1
  • Patrick Giraudeau
    • 1
  • Virginie Silvestre
    • 1
  • Titouan Jaunet-Lahary
    • 1
  • Véronique Ferchaud-Roucher
    • 2
  • Michel Krempf
    • 2
  • Serge Akoka
    • 1
  • Illa Tea
    • 1
  • Mohammed Boujtita
    • 1
    Email author
  1. 1.CNRS, Chimie et Interdisciplinarité: Synthèse, Analyse et Modélisation (CEISAM), UMR 6230LUNAM Université de NantesNantes Cedex 3France
  2. 2.Plateforme Spectrométrie de Masse, Institut de Recherche en Santé de l’Université de Nantes (IRS-UN)Université de NantesNantes Cedex 1France

Personalised recommendations