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Exploring the enantiomeric 13C position-specific isotope fractionation: challenges and anisotropic NMR-based analytical strategy

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Abstract

Trying to answer the intriguing and fundamental question related to chiral induction/amplification at the origin of homochirality in Nature: “Is there a relationship between enantiomeric and isotopic fractionation of carbon 13 in chiral molecules?” is a difficult but stimulating challenge. Although isotropic 13C-PSIA NMR is a promising tool for the determination of (13C/12C) ratios capable of providing key 13C isotopic data for understanding the reaction mechanisms of biological processes or artificial transformations, this method does not provide access to any enantiomeric 13C isotopic data unless mirror-image isomers are first physically separated. Interestingly, 13C spectral enantiodiscriminations can be potentially performed in situ in the presence of enantiopure entities as chiral-europium complexes or chiral liquid crystals (CLCs). In this work, we explored for the first time the capabilities of the anisotropic 13C-{1H} NMR using PBLG-based lyotropic CLCs as enantiodiscriminating media in the context of the enantiomeric position-specific 13C isotope fractionation (EPSIF), within the requested precision of the order of the permil. As enantiomeric NMR signals are discriminated on the basis of a difference of 13C residual chemical shift anisotropy (13C-RCSA) prior to being deconvoluted, analysis of enantiomeric mixtures becomes possible. The analytical potential of this approach when using poly-γ-benzyl-L-glutamate (PBLG) is presented, and the preliminary quantitative results on small model chiral molecules obtained at 17.5 T with a cryogenic NMR probe are reported and discussed.

Graphical abstract

A promising analytical approach based on anisotropic irm-13C-NMR spectrometry to potentially reveal the natural 13C/12C isotopic enantiofractionation effects in organic chiral molecules is proposed and discussed.

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Acknowledgements

The authors thank CNRS (INC) and its specific financial contribution to this project (ISOTOP 2018-2019 grant) as well as for its recurrent funding of science. They gratefully acknowledge Mathilde Grand (CEISAM) for help with irm-MS analysis and Achille Khalid for his participation to this project in the frame of his first year of master student’s internship at ICMMO, as well as the Université Paris-Saclay (formerly, Université de Paris-Sud) for its support.

Funding

This work was the subject of a specific grant from the CNRS as part of the ISOTOP 2018/ISOTOP 2019 program.

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Authors and Affiliations

  1. Université Paris-Saclay, Centre Scientifique d’Orsay, ICMMO, CNRS UMR 8182, RMN en Milieu Orienté, Bât. 410, rue du Doyen Georges Poitou, 91405, Orsay cedex, France

    Philippe Lesot & Philippe Berdagué

  2. Centre National de la Recherche Scientifique (CNRS), 3 rue Michel Ange, 75016, Paris, France

    Philippe Lesot

  3. Université de Nantes, CEISAM, CNRS UMR 6230, 44000, Nantes, France

    Virginie Silvestre & Gérald Remaud

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  1. Philippe Lesot
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  2. Philippe Berdagué
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Lesot, P., Berdagué, P., Silvestre, V. et al. Exploring the enantiomeric 13C position-specific isotope fractionation: challenges and anisotropic NMR-based analytical strategy. Anal Bioanal Chem 413, 6379–6392 (2021). https://doi.org/10.1007/s00216-021-03599-8

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