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  2. Online Charge-Generation Derivatization by Electrochemical Radical Cations of Thianthrene: Mass Spectrometry Imaging of Estrogens in Biological Tissues

Online Charge-Generation Derivatization by Electrochemical Radical Cations of Thianthrene: Mass Spectrometry Imaging of Estrogens in Biological Tissues

  • Anal Chem. 2024 Jul 20. doi: 10.1021/acs.analchem.4c02086.
Yingchao Liu 1 Jiahui Bai 1 Xiaoxia Dong 2 Yuqi Cao 1 Mingmai Bao 1 Yingjie Lu 3 Hui Zeng 4 Lixing Zhan 2 Yinlong Guo 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Organometallic Chemistry and National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
  • 2 CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  • 3 Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
  • 4 Comprehensive Exposure Research Center, School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
Abstract

Estrogens play a significant role in Endocrinology and oncology. Although separation methods coupled with mass spectrometry (MS) have emerged as a powerful tool for studying estrogens, imaging the spatial distributions of estrogens is crucial but remains challenging due to its low endogenous concentration and poor ionization efficiency. Charge-generation derivatization, such as N-alkylpyridinium quaternization and S-methyl thioetherification, represents a method wherein neutral molecules involving analytes and derivatization reagents undergo chemical reactions to establish permanent charges directly onto the analytes to improve detection sensitivity. Here, we developed a novel derivatization reagent, thianthrene (TT), which enabled oxidization to radical cations ([TT]•+) using an electrochemical method and completed the online charge-generation derivatization of estrogens on a mass spectrometry imaging platform. In this strategy, [TT]•+ can efficiently and selectively derivatize estrogens via an electrophilic aromatic substitution reaction. Results indicated that derivatization with [TT]•+ can significantly enhance imaging sensitivity (3 orders of magnitude), enabling the visualization of estrogen and its metabolites in ovarian and breast tissues. Furthermore, a higher mass intensity of these estrogens was captured in breast para-cancerous tissues than in cancerous tissues, which might provide estrogens spatial dimension information for further research on the initiation and progression of breast Cancer.

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