The aberrantly changed level of homocysteine (Hcy) triggers a variety of pathological symptoms and subsequently Hcy-related diseases. Direct and selective visualization of Hcy in biological systems is pivotal to understanding the pathological functions of Hcy at the molecular level. Herein, a general strategy was developed for the specific fluorescence imaging of Hcy through the combination of dual-binding sites and the introduction of a nitro group at the 6-position of the 7-diethylaminocoumarin fluorophore. Also, a series of novel fluorescent probes were exploited for monitoring Hcy with excellent selectivity, high sensitivity, and far-red/near-infrared fluorescence emission. Furthermore, fluorescence imaging of endogenous Hcy dynamics in living cells and in vivo was achieved, providing direct and solid evidence for the increasement of endogenous Hcy in type 2 diabetes mellitus and Alzheimer’s disease. This research will greatly advance the development and understanding of the molecular nexus between the Hcy metabolism cascade and the root causes of diseases related to Hcy.

中文翻译：

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活细胞和体内同型半胱氨酸特异性荧光成像的一般策略

同型半胱氨酸 (Hcy) 水平的异常变化引发多种病理症状，随后引发与 Hcy 相关的疾病。生物系统中 Hcy 的直接和选择性可视化对于在分子水平上理解 Hcy 的病理功能至关重要。在此，通过结合双结合位点和在 7-二乙氨基香豆素荧光团的 6 位引入硝基，开发了一种用于 Hcy 特异性荧光成像的通用策略。此外，开发了一系列新型荧光探针用于监测 Hcy，具有优异的选择性、高灵敏度和远红/近红外荧光发射。此外，活细胞和体内内源性 Hcy 动力学的荧光成像实现了，为2型糖尿病和阿尔茨海默病中内源性Hcy升高提供了直接而确凿的证据。这项研究将极大地促进 Hcy 代谢级联与 Hcy 相关疾病的根本原因之间的分子联系的发展和理解。