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.
Similar content being viewed by others
References
Richards JA, Evans DH (1975) Anal Chem 47(6):964–966
Mincey DW, Popovich MJ, Faustino PJ, Hurst MM, Caruso JA (1990) Anal Chem 62(11):1197–1200
Webster RD (2004) Anal Chem 76(6):1603–1610
Sandifer ME, Zhao M, Kim S, Scherson DA (1993) Anal Chem 65:2093–2095
Zhang X, Zwanziger JW (2011) J Magn Reson 208(1):136–147
Klod S, Ziegs F, Dunsch L (2009) Anal Chem 81(24):10262–10267
Albert K, Dreher E-L, Straub H, Rieker A (1987) Magn Reson Chem 25(10):919–922
Klod S, Dunsch L (2011) Magn Reson Chem 49(11):725–729
Klod S, Haubner K, Jaehne E, Dunsch L (2010) Chem Sci 1:743–750
Jahn S, Karst U (2012) J Chromatogr A 1259:16–49
Madsen KG, Olsen J, Skonberg C, Hansen SH, Jurva U (2007) Chem Res Toxicol 20(5):821–831
Simon H, Melles D, Jacquoilleot S, Sanderson P, Zazzeroni R, Karst U (2012) Anal Chem 84(20):8777–8782
James LP, Mayeux PR, Hinson JA (2003) Drug Metab Dispos 31(12):1499–1506
Nouri-Nigjeh E, Bischoff R, Bruins AP, Permentier HP (2011) Analyst 136(23):5064–5067
Yin H, Meng X, Xu Z, Chen L, Ai S (2012) Anal Methods 4(5):1445–1451
Rodriguez S, Santos A, Romero A, Vicente F (2012) Chem Eng J 213:225–234
Guengerich FP (2001) Chem Res Toxicol 14(6):611–650
Prenzler PD, Bramley R, Downing SR, Heath GA (2000) Electrochem Commun 2(7):516–521
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 762:39–46
Nematollahi D, Shayani-Jam H, Alimoradi M, Niroomand S (2009) Electrochim Acta 54(28):7407–7415
Bussy U, Ferchaud-Roucher V, Tea I, Krempf M, Silvestre V, Boujtita M (2012) Electrochim Acta 69:351–357
Novak M, Pelecanou M, Pollack L (1986) J Am Chem Soc 108:112–120
Frydman L, Scherf T, Lupulescu A (2002) Proc Natl Acad Sci USA 99:15858–15862
Giraudeau P, Shrot Y, Frydman L (2009) J Am Chem Soc 131:13902–13903
Queiroz LHK Jr, Queiroz DPK, Dhooghe L, Ferreira AG, Giraudeau P (2012) Analyst 137:2357–2361
Acknowledgments
The authors thank CNRS, the University of Nantes, and the French Ministry of Higher Education and Research for financial support.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
ESM 1
(PDF 230 kb)
Rights and permissions
About this article
Cite this article
Bussy, U., Giraudeau, P., Silvestre, V. et al. In situ NMR spectroelectrochemistry for the structure elucidation of unstable intermediate metabolites. Anal Bioanal Chem 405, 5817–5824 (2013). https://doi.org/10.1007/s00216-013-6977-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-013-6977-z