Fast 2D NMR spectroscopy for complex mixtures

Abstract : Metabolomics is a recent area of research, which aims at analyzing the entirety of molecules involved in chemical reactions in an organism. Nuclear Magnetic Resonance (NMR) is widely used in metabolomics nowadays thanks to a methodology based on one-dimensional (1D) NMR. However, 1D spectra of complex mixtures, like biological extracts or fluids, are characterized by important overlap between peaks, which can be detrimental to the identification and quantification of molecules of interest. Two-dimensional (2D) NMR can be used to reduce the risk of overlap. However, the duration of 2D experiments is often prohibitive for metabolomics studies. Several approaches exist to reduce the duration of 2D experiments, but they have not been evaluated so far for metabolomics. In this thesis, we have shown the usefulness of fast 2D NMR for metabolomics and optimized its performances. Two fast 2D NMR approaches have been evaluated, ultrafast 2D NMR and non-uniform sampling. In a study with synthetic samples, we first demonstrated the usefulness of 2D NMR compared to 1D NMR, then we showed that the experimental time of 2D spectra could be reduced with fast 2D NMR approaches without loss of information. Then we optimized the use of fast 2D NMR for complex mixture analysis. First, we developed a new pulse sequence with ultrafast 2D NMR of proton, in order to suppress the diagonal peaks, which can overlap with correlation peaks and therefore reduce the information content of 2D spectra. Then non-uniform sampling was used to increase up to 32 times the resolution in the indirect dimension without increasing the experimental time and without loss of sensitivity or repeatability. Finally, we worked on automating the determination of relaxation constants in complex mixture. These tools open promising perspectives for high-throughput metabolomics of complex biological samples.
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Contributor : Adrien Le Guennec <>
Submitted on : Wednesday, September 2, 2015 - 1:17:31 PM
Last modification on : Monday, February 25, 2019 - 9:42:01 PM
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Adrien Le Guennec. Fast 2D NMR spectroscopy for complex mixtures. Chemical Sciences. Ecole Polytechnique, 2015. English. ⟨tel-01191697⟩

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