Ligand-Directed Approach to Activity-Based Sensing: Developing Palladacycle Fluorescent Probes That Enable Endogenous Carbon Monoxide Detection
Ligand-Directed Approach to Activity-Based Sensing: Developing Palladacycle Fluorescent Probes That Enable Endogenous Carbon Monoxide Detection
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DOI：
10.1021/jacs.0c06405
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发表时间：
2020-09-16
影响因子：
15
通讯作者：
Chang, Christopher J.
中科院分区：
文献类型：
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作者：
Morstein, Johannes;Hofler, Denis;Chang, Christopher J.
一氧化碳（CO）是一种新兴的气体递质和活性碳，具有广泛的抗炎、细胞保护和神经递质功能，沿着有治疗心血管疾病的潜力。CO化学在生物学和医学中的研究相对于其他突出的气体递质，如NO和H2S仍然具有挑战性，在很大程度上是由于在复杂的生命系统中直接可视化这种瞬态和自由扩散的小分子的可用工具的限制。在这里，我们报告了一个配体导向的活性为基础的传感（ABS）的方法，通过钯介导的羰基化化学CO检测。具体而言，设计和合成了一系列ABS探针，其在钯-配体环境中具有系统性改变（例如，sp（3）-S，sp（3）-N，sp（2）-N）建立了钯杂环在生理条件下与CO选择性反应性的结构-活性关系。这些基础研究导致了一种优化探针的开发，称为一氧化碳探针-3酯吡啶（COP-3E-Py），其能够对活细胞和大脑环境中的CO释放进行成像，包括监测触发果蝇大脑中突触前多巴胺释放的内源性CO产生。这项工作提供了一个独特的工具，用于研究CO在生活系统中，并建立了实用的合成方法的方法，以活性为基础的传感使用有机金属化学的原则。
Carbon monoxide (CO) is an emerging gasotransmitter and reactive carbon species with broad anti-inflammatory, cytoprotective, and neurotransmitter functions along with therapeutic potential for the treatment of cardiovascular diseases. The study of CO chemistry in biology and medicine relative to other prominent gasotransmitters such as NO and H2S remains challenging, in large part due to limitations in available tools for the direct visualization of this transient and freely diffusing small molecule in complex living systems. Here we report a ligand-directed activity-based sensing (ABS) approach to CO detection through palladium-mediated carbonylation chemistry. Specifically, the design and synthesis of a series of ABS probes with systematic alterations in the palladium-ligand environment (e.g., sp(3)-S, sp(3)-N, sp(2)-N) establish structure-activity relationships for palladacycles to confer selective reactivity with CO under physiological conditions. These fundamental studies led to the development of an optimized probe, termed Carbon Monoxide Probe-3 Ester Pyridine (COP-3E-Py), which enables imaging of CO release in live cell and brain settings, including monitoring of endogenous CO production that triggers presynaptic dopamine release in fly brains. This work provides a unique tool for studying CO in living systems and establishes the utility of a synthetic methods approach to activity-based sensing using principles of organometallic chemistry.