Citation: Yanhui Zhong, Peisi Xie, Chengyi Xie, Lei Guo, Weiwei Chen, Shuyi Wang, Xiaoxiao Wang, Fuyue Wang, Zian Lin, Gongke Li, Zongwei Cai. Rigid urea-based structures drive analysis of chiral amino acids[J]. Chinese Chemical Letters, ;2026, 37(2): 112039. doi: 10.1016/j.cclet.2025.112039 shu

Rigid urea-based structures drive analysis of chiral amino acids

Yanhui Zhong ^{a, b} ,
Peisi Xie ^b ,
Chengyi Xie ^b ,
Lei Guo ^b ,
Weiwei Chen ^b ,
Shuyi Wang ^a ,
Xiaoxiao Wang ^b ,
Fuyue Wang ^b ,
Zian Lin ^{a, *,} ,
Gongke Li ^{c, *,} ,
Zongwei Cai ^{b, d, *,}

a.
Ministry of Education Key Laboratory of Analytical Science for Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, College of Chemistry, Fuzhou University, Fuzhou 350108, China
b.
State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong 999077, China
c.
School of Chemistry, Sun Yat-sen University, Guangzhou 510006, China
d.
Eastern Institute of Technology, Ningbo 315100, China

zianlin@fzu.edu.cn

cesgkl@mail.sysu.edu.cn

zwcai@hkbu.edu.hk

Received Date: 8 May 2025
Revised Date: 28 September 2025
Accepted Date: 29 October 2025
Available Online: 30 October 2025

Figures(4)

Chiral amino acids (AAs) serve as essential building blocks of proteins and play vital physiological roles in living organisms. To achieve accurate, rapid, and high-throughput analysis of chiral AAs, this work proposed a methylbenzyl isocyanate (MBIC) derivatization strategy coupled with ultra-high performance liquid chromatography-mass spectrometry or trapped ion mobility spectrometry-mass spectrometry. The integration of a chiral carbon atom with a rigid urea-based structure can significantly enhance the separation of chiral MBIC-labeled AA enantiomers. This phenomenon can be attributed to the labeled l-AAs allow the carboxyl group to form intramolecular hydrogen bonds with the amino group in the rigid urea-based structure, whereas labeled d-AAs are unable to form such bonds. The method based on MBIC derivatization coupled with ultra-performance liquid chromatography-tandem mass spectrometry achieved simultaneous separation of 19 pairs of chiral AAs using only a C18 column within 30 min, enabling quantitatively detect twelve types of chiral AAs in the serum of healthy humans and Parkinson's patients. The distribution of twenty-four chiral AAs is observed in mouse brain using MBIC labeling-based matrix-assisted laser desorption/ionization-trapped ion mobility spectrometry-mass spectrometry imaging without prior separation. Our work elucidates the principles governing the separation of chiral AAs using derivatization methods, providing valuable guidance for the separation of chiral compounds.
- Chiral amino acids,
- Rigid urea-based structures,
- Intramolecular hydrogen bonds,
- UPLC-MS,
- MALDI-TIMS-MS
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