Carbon Residual Chemical Shift Anisotropy as an Analytical Tool for Anomeric Differentiation and...

This methodological development establishes carbon residual chemical shift anisotropy (RCSA) as an effective analytical tool for the unambiguous anomeric differentiation and enantiodiscrimination of carbohydrates and amino acids aligned in an aqueous disodium folate (DSF) liquid crystal. The broad applicability of the proposed methods was assured across the structural analyses of three different aspects in the H₂O/D₂O solvent system: anomeric differentiation of carbohydrates, enantiodiscrimination of amino acids, and configurational analysis of carbohydrates. So far, H₂O/D₂O-compatible alignment media have not been employed for molecular structure analysis by the RCSA of small molecules. The analyses were carried out using the RCSAs measured in the isotropic phase and in the chromonic-like lyotropic liquid crystalline phase of DSF. The RCSA data obtained in the aligned DSF liquid crystal not only enable a clear distinction between the α- and β-anomers of carbohydrates but also remarkably show that the liquid crystalline phase of DSF is capable of simultaneously accommodating both anomers in different orientations. The generalized cosine beta values obtained in enantiodiscrimination clearly indicate substantial enantiodifferentiation between D and L enantiomers. Collectively, these findings expand the toolbox of NMR-focused analytical chemists, making it a powerful analytical tool that complements Nuclear Overhauser effects and J-couplings for the stereochemical analysis of flexible molecules in water-compatible systems.