College of Chemical and Materials Engineering, Xuchang University, Xuchang 461000, PR China.
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China.
Anal Chem. 2024 Nov 5;96(44):17657-17664. doi: 10.1021/acs.analchem.4c03685. Epub 2024 Oct 23.
Monitoring peroxynitrite (ONOO) fluctuations is particularly important for assessing pathological progression and oxidative damage due to their crucial role in maintaining the redox balance of organisms. However, due to the lack of efficient tools for differentially monitoring ONOO fluctuations at different concentration ranges in vivo, the precise detection of endogenous ONOO fluctuations under pathological conditions in living systems remains challenging. Herein, we rationally designed a double-enhanced emission cascade activatable near-infrared (NIR) fluorescent probe () for the measurement of ONOO, which consists of a borate ester response group and a malononitrile hemicyanine fluorophore. Especially, after sequential oxidative hydrolysis of the borate ester group and xanthene skeleton, exhibited a sequentially double-enhanced NIR emission response at 776 and 625 nm for different ONOO concentration ranges. Moreover, revealed excellent and promising performance for ONOO in terms of high selectivity, sensitivity, and reaction rate ( = 28.2 M s). Motivated by the two-step emission signal enhancement and large wavelength shift in the NIR region, enabled discriminative imaging of ONOO with the low and high concentrations in living cells. Importantly, was successfully applied for assessing the pathological progression of isoniazid and acetaminophen-induced liver damage in vivo by detecting the endogenous different ONOO levels. Overall, this study not only demonstrates the first double-enhanced emission cascade activatable NIR fluorescent probe for measuring the dynamic variation of ONOO in related diseases but also shows great potential as an effective molecular tool for evaluating the various stages of drug-induced liver damage.
监测过氧亚硝酸盐（ONOO）的波动对于评估病理进展和氧化损伤非常重要，因为它们在维持生物体的氧化还原平衡方面起着至关重要的作用。然而，由于缺乏有效工具来在体内不同浓度范围内差异监测 ONOO 的波动，因此在活系统中精确检测病理条件下的内源性 ONOO 波动仍然具有挑战性。在此，我们合理设计了一种双增强发射级联激活的近红外（NIR）荧光探针（），用于测量 ONOO，它由硼酸酯反应基团和丙二腈半花青荧光团组成。特别是，在硼酸酯基团和呫吨骨架的顺序氧化水解之后，在 776 和 625nm 处分别对不同的 ONOO 浓度范围表现出顺序双增强的 NIR 发射响应。此外，在 ONOO 方面，表现出出色且有前途的高选择性、灵敏度和反应速率（=28.2M s）。受两步发射信号增强和 NIR 区域大波长位移的启发，能够在活细胞中对 ONOO 的低浓度和高浓度进行有区别的成像。重要的是，通过检测内源性不同的 ONOO 水平，成功地应用于评估异烟肼和对乙酰氨基酚诱导的肝损伤的体内病理进展。总的来说，这项研究不仅展示了用于测量相关疾病中 ONOO 动态变化的首个双增强发射级联激活的近红外荧光探针，而且还显示出作为评估药物诱导肝损伤各个阶段的有效分子工具的巨大潜力。
