Visualizing ClO- fluctuations in drug-induced liver injury and bacterium via a robust ratiometric fluorescent probe

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Abstract

As a type of reactive oxygen species, hypochlorous acid (ClO-) plays an important role in sterilization, disinfection and protection in organisms. However, excessive production of ClO- is closely related to various diseases. In this work, we have designed a robust ratiometric fluorescent probe, RDB-ClO, using the excited-state intramolecular proton transfer (ESIPT) strategy. RDB-ClO was achieved by modifying 2-(2-(benzo[d]thiazol-2-yl)-6-(diethylamino)-3-oxo-3H-xanthen-9-yl) benzoic acid (RDB-OH) with a 1-naphthoyl chloride group, specifically for the sensitive detection of ClO-. In the presence of ClO-, RDB-ClO demonstrated relatively good performance, showing swift response time (35 s), low detection limit of 5.1 nM and high selectivity towards ClO-. Notably, the convenience and accessibility detection of ClO- has been implemented using test strip and agarose probe. RDB-ClO effectively tracked both endogenous and exogenous ClO- in HeLa cells, HepG2 cells and zebrafish. Additionally, it is successfully applied to detect changes of exogenous ClO- content in E. coli. and acetaminophen (APAP)-induced liver injury in mice. The development of RDB-ClO represents a promising molecular tool for studying the pathogenesis of DILI and biotransformation of ClO- in bacteria.

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通过稳健的比率荧光探针观察药物引起的肝损伤和细菌中的 ClO- 波动。
作为一种活性氧,次氯酸(ClO-)在生物体内的杀菌、消毒和保护方面发挥着重要作用。然而,ClO-的过量产生与多种疾病密切相关。在这项工作中,我们利用激发态分子内质子转移(ESIPT)策略设计了一种稳健的比率荧光探针 RDB-ClO。RDB-ClO 是通过在 2-(2-(苯并[d]噻唑-2-基)-6-(二乙基氨基)-3-氧代-3H-氧杂蒽-9-基)苯甲酸(RDB-OH)上修饰 1-萘甲酰氯基团而实现的,专门用于灵敏检测 ClO-。在 ClO- 存在的情况下,RDB-ClO 表现出较好的性能,响应时间短(35 秒),检测限低(5.1 nM),对 ClO- 具有高选择性。值得注意的是,利用试纸和琼脂糖探针实现了对 ClO- 的便捷检测。RDB-ClO 能有效追踪 HeLa 细胞、HepG2 细胞和斑马鱼体内的内源性和外源性 ClO-。此外,它还成功地应用于检测大肠杆菌中外源性 ClO- 含量的变化以及对乙酰氨基酚(APAP)诱导的小鼠肝损伤。RDB-ClO 的开发为研究 DILI 的发病机制和细菌中 ClO- 的生物转化提供了一种前景广阔的分子工具。
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来源期刊
CiteScore
8.40
自引率
11.40%
发文量
1364
审稿时长
40 days
期刊介绍: Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy (SAA) is an interdisciplinary journal which spans from basic to applied aspects of optical spectroscopy in chemistry, medicine, biology, and materials science. The journal publishes original scientific papers that feature high-quality spectroscopic data and analysis. From the broad range of optical spectroscopies, the emphasis is on electronic, vibrational or rotational spectra of molecules, rather than on spectroscopy based on magnetic moments. Criteria for publication in SAA are novelty, uniqueness, and outstanding quality. Routine applications of spectroscopic techniques and computational methods are not appropriate. Topics of particular interest of Spectrochimica Acta Part A include, but are not limited to: Spectroscopy and dynamics of bioanalytical, biomedical, environmental, and atmospheric sciences, Novel experimental techniques or instrumentation for molecular spectroscopy, Novel theoretical and computational methods, Novel applications in photochemistry and photobiology, Novel interpretational approaches as well as advances in data analysis based on electronic or vibrational spectroscopy.
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