中国科学院大连化物所发表检测细胞内氧化还原变化研究的综述

中国科学院大连化学物理研究所分子反应动力学国家重点实验室研究员韩克利团队在模拟谷胱甘肽过氧化物酶活性中心构建用于检测细胞内氧化还原状态变化的小分子荧光探针方面的系列研究工作受到了国际同行的广泛关注。近日，该团队受邀在Accounts of Chemical Research 杂志上发表综述文章Redox-Responsive Fluorescent Probes with Different Design Strategies(Acc. Chem. Res.2015, 48, 1358−1368)。

细胞内的氧化还原平衡主导着生物体的各种生理病理过程，而参与这一平衡的活性氧具有反应活性高、半衰期短等特点。因此，检测细胞内的氧化还原状态变化是一项非常具有挑战性又有重要生物医学意义的研究工作。近年来，韩克利研究组一直致力于发展用于检测活细胞内氧化还原状态变化的小分子荧光探针，模拟谷胱甘肽过氧化物酶的活性中心硒、碲类似物，采用不同的荧光作用机理，发展了一系列具有选择性好、灵敏度高、近红外吸收、快速响应等特点的荧光探针，并相继在J. Am. Chem. Soc.、Chem. Commun.、Phys. Chem. Chem. Phys.等杂志上发表了一系列文章。

该综述文章根据荧光探针的不同设计策略，系统地总结了韩克利研究组近年来在发展检测活细胞内氧化还原状态变化的小分子荧光探针以及对于荧光探针的作用机理方面的研究进展。该篇综述是第一篇比较系统地概述“检测细胞内氧化还原变化的小分子荧光探针”的文章，对未来发展更多性能优良的响应氧化还原状态变化的荧光探针具有非常重要的指导意义。

原文链接:

Redox-Responsive Fluorescent Probes with Different Design Strategies

原文摘要：

In an aerobic organism, reactive oxygen species (ROS) are an inevitable metabolic byproduct. Endogenously produced ROS have a significant role in physiological processes, but excess ROS can cause oxidative stress and can damage tissue. Cells possess elaborate mechanisms to regulate their internal redox status. The intracellular redox homeostasis plays an essential role in maintaining cellular function. However, moderate alterations in redox balance can accompany major transitions in a cell’s life cycle. Because of the role of ROS in physiology and in pathology, researchers need new tools to study redox chemistry in biological systems.

In recent years, researchers have made remarkable progress in developing new, highly sensitive and selective fluorescent probes that respond to redox changes, and in this Account we highlight related research, primarily from our own group. We present an overview of the design, photophysical properties, and fluorescence transduction mechanisms of reported molecules that probe redox changes. We have designed and synthesized a series of fluorescent probes for redox cycles in BioLogical systems relying on the active center of glutathione peroxidase (GPx). We have also constructed probes based on the oxidation and reduction of hydroquinone and of 2,2,6,6-tetramethylpiperidinooxy (TEMPO). Most of these probes exhibit high sensitivity and good selectivity, absorb in the near-infrared, and respond rapidly. Such probes are useful for confocal fluorescence microscopy, a dynamic imaging technique that could allow researchers to observe biologically important ROS and antioxidants in real time. This technique and these probes provide potentially useful tools for exploring the generation, transport, physiological function, and pathogenic mechanisms of ROS and antioxidants.

We also describe features that could improve the properties of redox-responsive fluorescent probes: greater photostability; rapid, dynamic, cyclic and ratiometric responses; and broader absorption in the near-IR region. In addition, fluorescent probes that include organochalcogens such as selenium and tellurium show promise for a new class of fluorescent redox probes that are both chemically stable and robustly reversible. However, further investigations of the chemical and fluorescence transduction mechanisms of selenium-based probes in response to ROS are needed.

DOI: 10.1021/acs.accounts.5b00009

作者：韩克利