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

Abstract

Enantiomeric analysis is of great significance in chemistry, chemical biology and pharmaceutical research. We herein propose a chiral ¹⁹F NMR tag containing an amino reactive NHS group to discriminate the enantiomeric amino acids under physiological conditions by NMR spectroscopy. The chiral ¹⁹F 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 ¹⁹F atom and is therefore decoded by the ¹⁹F reporter and manifested in the distinct ¹⁹F chemical shift. The chemical shift difference (ΔΔδ) of the chiral ¹⁹F 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 ¹⁹F NMR tag to the stereospecific environment surrounding the individual amino acids. The distinguishable chemical shift produced by the chiral ¹⁹F NMR tag permits simultaneous discrimination and quantification of the enantiomeric amino acids in a mixture. The high fidelity of the chiral ¹⁹F NMR tag affords high-accuracy determination of the enantiomeric composition of amino acids by simple 1D NMR under physiological conditions.