Liu Yingchao, Bai Jiahui, Dong Xiaoxia, Cao Yuqi, Bao Mingmai, Lu Yingjie, Zeng Hui, Zhan Lixing, Guo Yinlong
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.
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.
Anal Chem. 2024 Jul 20. doi: 10.1021/acs.analchem.4c02086.
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 -alkylpyridinium quaternization and -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.
雌激素在内分泌学和肿瘤学中发挥着重要作用。尽管分离方法与质谱联用已成为研究雌激素的有力工具，但对雌激素的空间分布进行成像至关重要，但由于其内源浓度低和电离效率差，仍然具有挑战性。电荷生成衍生化，如 - 烷基吡啶季铵化和 - 甲基硫醚化，是一种方法，其中涉及分析物和衍生化试剂的中性分子发生化学反应，直接在分析物上建立永久电荷以提高检测灵敏度。在此，我们开发了一种新型衍生化试剂噻蒽（TT），它能够通过电化学方法氧化为自由基阳离子（[TT]），并在质谱成像平台上完成雌激素的在线电荷生成衍生化。在该策略中，[TT] 可通过亲电芳香取代反应高效且选择性地衍生化雌激素。结果表明，用 [TT] 衍生化可显著提高成像灵敏度（3 个数量级），从而能够可视化卵巢和乳腺组织中的雌激素及其代谢物。此外，在乳腺癌旁组织中捕获的这些雌激素的质量强度高于癌组织，这可能为乳腺癌的发生和发展的进一步研究提供雌激素空间维度信息。
