trans-4-Fluoro-l-proline: A Sensitive ¹⁹F NMR Probe for the Rapid Simultaneous Enantiomeric Analysis of Multicomponent Amines

Abstract

Simultaneous enantiomeric analysis is especially important for medicine, food security, and life science. Chiral analysis of multicomponent amine mixtures still faces many challenges. Here, our work demonstrates for the first time that a novel chiral derivatizing agent CDApro based on trans-4-fluoro-l-proline (trans4Fpro) has been successfully used for the rapid simultaneous analysis of 22 chiral nonamino acid (non-AA) amines, multicomponent l/d-AAs, or mirror-image dipeptides in a mixture, as well as amines with chiral centers several carbons remote to the amino group. Furthermore, determination of enantiomeric purity and quantification of chiral amines can be made using CDApro, which serves as a robust and powerful reagent for the differentiation of multicomponent chiral amines.

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

“…In addition, the chemical shifts are generally concentration-dependent due to weak interactions between amino acids and sensors. The chemical shift differences of the enantiomeric amino acids encoded in the chiral 19 F NMR tag with a bandwidth of 2.8 ppm is also larger than the recent chiral 19 F probe of a trans-4fluoro-L-proline derivative with a range of 0.6 ppm, 37 which shows high performance in discriminating the chiral amines in the organic solvent. The results indicate the spatial distance between the stereogenic center containing the 19 F reporter, and the chiral center of amino acids is a key factor in the discrimination of chiral molecules by 19 F NMR.…”

“…A just-accepted report uses a chiral 19 F probe in the formation of Schiff base products with the amino groups in organic solvents to quantify the chiral amines. 37 The complete transformation of amines to Schiff base products and the stability of Schiff base complexes in aqueous solution remains elusive. The previous work showed that qualitative and quantitative analyses of L-amino acids in biofluids by a reactive 19 F tag are feasible in aqueous solution.…”

“…These methods are barely suitable for the biological assay under physiological conditions. A just-accepted report uses a chiral 19 F probe in the formation of Schiff base products with the amino groups in organic solvents to quantify the chiral amines . The complete transformation of amines to Schiff base products and the stability of Schiff base complexes in aqueous solution remains elusive.…”

Solvent Effects Used for Optimal Simultaneous Analysis of Amino Acids via 19F NMR Spectroscopy

“…14 In our previous work, we found the influence of different solvents on the enantiodifference values of diastereoisomers. 2 Moreover, the resolution of 19 F NMR spectroscopy of a mixture solution was also assuredly solvent-dependent. 15,16 This is maybe due to the hydrogen bonds between nitrogen atoms and solvent molecules.…”

“…NMR-active isotope 19 F nuclei with 100% natural abundance exhibit a wide chemical shift range (∼400 ppm), which is exquisitely sensitive to the electronic microenvironment . These merits make 19 F NMR incredibly useful in the fields of analytical chemistry and chemical biology, such as the analysis of a complex multicomponent mixture, − quantification of hydrogen bonds, and the conformational investigation of proteins or nucleic acids. − …”