Precise Synthesis of GSH-Specific Fluorescent Probe for Hepatotoxicity Assessment Guided by Theoretical Calculation
2019
Chen, Jiao | Wang, Zesi | She, Mengyao | Liu, Mengdi | Zhao, Zebin | Chen, Xi | Liu, Ping | Zhang, Shengyong | Li, Jianli
Drug-induced hepatotoxicity is the main cause of acute liver injury, and its early diagnosis is indispensable in pharmacological and pathological studies. As a hepatotoxicity indicator, the GSH distribution in the liver could reflect the damage degree in situ. In this work, we have provided a theoretical design strategy to determine the generation of photo-induced electron transfer mechanism and achieve high selectivity for the target. After that, we precisely synthesized a novel near-infrared fluorescent probe BSR1 to specifically monitor endogenous GSH and hepatotoxicity in biosystem with a moderate fluorescent quantum yield (Φ = 0.394) and low detection limit (83 nM) under this strategy. Moreover, this mapping method for imaging GSH depletion in vivo to assay hepatotoxicity may provide a powerful molecular tool for early diagnosis of some diseases and contribute to assay hepatotoxicity for the development of new drugs. Importantly, this theoretical calculation-guided design strategy may provide an effective way for the precise synthesis of the target-specific fluorescent probe and change this research area from “trial-and-error” to concrete molecular engineering.
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