CAREER: Development of Single-Molecule Fluorescence Imaging for Studying Inorganic, Organic, and Organometallic Reaction Mechanisms

这个无机、生物无机和有机金属化学项目的奖项支持加州大学欧文分校的Suzanne Blum教授将单分子荧光显微镜应用于化学界广泛感兴趣的反应机制的研究。目前可用的研究分子整体性质的技术，例如系综光谱，存在两个主要缺点：(1)仪器动态范围导致无法检测混合物中微量（低于~1%）成分；(2)缺乏关于哪些成分负责反应性和催化的信息。观察催化中间体的困难可以用哈尔彭规则来概括：“如果你能观察或分离出一种中间体，那么它不太可能与催化有关。”单分子方法规避了哈尔彭规则，因为可以用光谱方法探测微量物质，而不管这些中间体是否积累到集合光谱所必需的水平。同样，单分子技术允许直接观察中间体，而不管它们在反应坐标上的位置（例如，在速率决定步骤之后）和十亿分之一的数量。尽管《科学》杂志最近的一期特刊认识到单分子显微镜在回答生化问题方面的新兴力量，但这些技术在回答化学问题方面的潜力实际上尚未开发。提出的研究提供了一种研究一系列反应的通用方法，通过将荧光标签附着在试剂上并使用全内反射（TIRF）显微镜来监测单个共价键形成事件。几种不同的具有代表性的合成重要的有机金属反应类型将被检查，包括烯烃聚合和芳烃胺化。此外，由于使用了TIRF，这些单分子实验将增强我们对表面化学和表面/溶液屏障催化作用的理解。通过专业发展计划，研究生助教与PI合作，参与最高水平的课程和讲座设计。教学法的讨论和影响的评估起着关键作用。从长远来看，该项目提高了社区学院、大学和K-12教师的技能。通过专业发展计划，研究生助教与PI合作，参与最高水平的课程和讲座设计。教学法的讨论和影响的评估起着关键作用。从长远来看，该项目提高了社区学院、大学和K-12教师的技能。

This award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports work by Professor Suzanne Blum at the University of California, Irvine, to apply single-molecule fluorescence microscopy in the study of mechanisms of reactions which are of broad interest to the chemical community. Currently available techniques that study the properties of molecules en masse, e.g. ensemble spectroscopy, suffer from two major drawbacks: (1) instrument dynamic range that leads to an inability to detect minor (under ~1%) components in mixtures; and (2) lack of information on which components are responsible for reactivity and catalysis. The difficulty in observing catalytic intermediates is summarized by Halpern's Rule: "If you can observe or isolate an intermediate, it is unlikely to be catalytically relevant." Single-molecule approaches circumvent Halpern's Rule, because trace quantities of material can be probed spectroscopically, regardless of whether these intermediates accumulate to a level necessary for ensemble spectroscopy. Similarly, single molecule techniques permit direct observation of intermediates regardless of their position on the reaction coordinate (e.g., after the rate-determining step) and in part-per-billion quantities. Although a special issue of Science recently recognized the emerging power of single-molecule microscopy to answer biochemical questions, the potential of these techniques to answer chemical questions remains virtually untapped. The proposed research provides a general method to study a range of reactions, by attaching fluorescent tags to reagents and using total internal reflectance (TIRF) microscopy to monitor individual covalent bond forming events. Several different representative types of synthetically important organometallic reactions will be examined, including olefin polymerization and arene amination. Additionally, because TIRF is used, these single-molecule experiments will enhance our understanding of surface chemistry, and catalysis at the surface/solution barrier. Through a professional development program, graduate student teaching assistants work with the PI to participate in curriculum and lecture design at the highest levels. Discussion of pedagogy and assessment of impact play key roles. In the long term, the program improves the skills of community college, university, and K-12 teachers.Through a professional development program, graduate student teaching assistants work with the PI to participate in curriculum and lecture design at the highest levels. Discussion of pedagogy and assessment of impact play key roles. In the long term, the program improves the skills of community college, university, and K-12 teachers.