Simultaneous Discrimination and Quantification of Enantiomeric Amino Acids under Physiological Conditions by Chiral 19 F NMR Tag.

Enantiomeric analysis is of great significance in chemistry, chemical biology and pharmaceutical research. We herein propose a chiral F NMR tag containing an amino reactive NHS group to discriminate the enantiomeric amino acids under physiological conditions by NMR spectroscopy. The chiral F NMR tag readily forms stable amide products with the amino acids in aqueous solution. The stereospecific chemistry of enantiomeric amino acids is discriminated by a stereogenic carbon bonded with a F atom and is therefore decoded by the F reporter and manifested in the distinct F chemical shift. The chemical shift difference (ΔΔδ) of the chiral F NMR tag derived enantiomeric amino acids variants has a broad chemical shift range between -1.13 to 1.68 ppm, indicating the high sensitivity of the chiral F NMR tag to the stereospecific environment surrounding the individual amino acids. The distinguishable chemical shift produced by the chiral F NMR tag permits simultaneous discrimination and quantification of the enantiomeric amino acids in a mixture. The high fidelity of the chiral F NMR tag affords high-accuracy determination of the enantiomeric composition of amino acids by simple 1D NMR under physiological conditions.