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

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. 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.