Chiral analysis of amino acid enantiomers is essential due to their frequently divergent biological activities. However, ion mobility spectrometry–mass spectrometry (IMS–MS) cannot directly resolve underivatized amino acid enantiomers due to their identical physicochemical properties. This study developed a derivatization-based analytical method utilizing (S)-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester ((S)-NIFE) as a chiral derivatization agent to achieve the stereoselective modification of amino acids. The resulting diastereomers form metal ion adducts, which enhance collision cross section differences and enable separation via trapped ion mobility spectrometry and time-of-flight mass spectrometry (TIMS–MS). The differential impact of alkali metal ion adduction (Na+, K+, Rb+, and Cs+) on chiral separation was investigated, revealing that Na+ adducts provide optimal enantioselective recognition (average resolution, Rpp = 2.02). The established method achieved separation for 30 chiral amino acids, demonstrating faster speed, broader coverage, and superior resolution compared with existing approaches. When applied to rat blood samples from chlorfenapyr-induced toxicity models, the method successfully detected d-Arg, d-Ile, d-Leu, d-Phe, and d-Met, confirming its practical utility in toxicological diagnostics and biomarker discovery.

**Abstract:** This research proposes a novel approach to kinetic resolution of enantiomers, leveraging Adaptive Frequency Oscillatory Cooling (AFOC) within microfluidic reactors to enhance reaction selectivity and throughput. AFOC utilizes precisely controlled oscillatory temperature gradients to modulate reaction kinetics, preferentially promoting the reaction of one enantiomer over the other. This method, combining established kinetic resolution principles with advanced microfluidics and optimized oscillatory temperature control, demonstrates superior enantiomeric excess (ee) and reaction rates compared to traditional methods, potentially revolutionizing fine chemical synthesis and pharmaceutical production.

Neuropsychopharmacology - Carvone derived cannabidiol enantiomers as novel anticonvulsants

Publication date: Available online 17 November 2025 Source: Journal of Chromatography A Author(s): Yutaka Umakoshi, Yoshihiro Izumi, Tomomi Hashidate-Yoshida, Hideo Shindou, Takeshi Bamba

Nature Communications - DFT calculations and theory do not support enantiospecificity in NMR J-coupling constants