A new type of molecular probes for catching reactive radicals

自由基中间体在许多化学和生物过程中起着关键作用，它们的检测和定量对于燃烧、大气和室内化学、反应机理(包括催化--例如多相催化和最近发展的光氧化还原催化)、生物和药物化学(例如，监测氧化应激)至关重要。然而，自由基通常是非常短暂的，不能直接观察到，特别是在复杂的真实系统中。自由基的检测通常采用自旋捕捉技术和电子顺磁共振波谱相结合的方法，这一方法自20世纪60年代以来得到了成功的应用。近年来，质谱学被提出为一种更灵敏和信息更丰富的自旋捕捉检测方法。然而，由于质谱学不需要未配对的电子进行检测(与EPR光谱学不同)，传统的自旋陷阱不太适合这一目的。令人惊讶的是，这一点被研究界忽视了。我们最近设计了一种不同类型的陷阱来检测自由基。与更传统的方法相比，我们的新捕捉器在检测的稳定性、灵敏度和选择性方面有了显著的改进，在远低于当前技术检测极限的情况下，提供了以前无法获得的关于气相中自由基中间体的物种结构信息。在这个项目中，我们将把我们的新方法(迄今仅用于气相自由基)扩展到液体反应，其中最令人兴奋的应用包括研究生化机制(通过氧化应激监测或免疫自旋捕获)，探索催化反应的机制，以及观察与大气和等离子体化学相关的气-水界面反应。我们相信，这将导致我们对自由基过程机制的理解发生一步变化，并将为建立新的合作和新的研究领域打开机会。该项目中的挑战包括合成、设计合适的分析方法以及新探针在实际系统中的稳定性。然而，失败的总体风险很低，因为新方法的可行性已经在我们的初步工作中得到了证实。

Free radical intermediates play a key role in many chemical and biological processes, and their detection and quantification is critical for combustion, atmospheric and indoor chemistry, reaction mechanisms (including catalysis - such as heterogeneous catalysis and a recently developed area of photoredox catalysis), biological and medicinal chemistry (e.g., monitoring oxidative stress). However, free radicals are often very short lived, and cannot be observed directly, particularly in complex real systems. Free radicals are usually detected using spin trapping technique in conjunction with EPR spectroscopy, a method which has been successfully used since 1960s.In recent years, mass spectrometry was proposed as a more sensitive and informative detection method for spin trapping. However, as mass spectrometry does not require unpaired electrons for detection (unlike EPR spectroscopy), the conventional spin traps are not well-suited for this purpose. This point has surprisingly been overlooked by the research community. We have recently designed a different type of traps for radical detection. Our new traps offer dramatic improvements in stability, sensitivity and selectivity of detection compared to the more conventional methods, providing previously unavailable speciated structural information about radical intermediates in the gas phase at concentrations well below the detection limit of current techniques.In this project, we will expand our new method (which has so far been only used with gas phase radicals) to liquid phase reactions, where the most exciting applications include studying biochemical mechanisms (through oxidative stress monitoring or immuno spin trapping), exploring mechanisms of catalytic reactions and looking at reactions at air-water interface, relevant to atmospheric and plasma chemistry. We believe this will lead to a step change in our understanding of mechanisms of free radical processes and will open up opportunities to establish new collaborations and new areas of research. The challenges in this project include synthesis, design of appropriate analysis method, and stability of the new probes in real systems. However the overall risk of failure is low as the feasibility of the new method has already been established in our preliminary work.