Binuclear Copper-O2 Intermediates: Thermodynamic and Mechanistic Insights

项目总结： 与氧气反应的铜酶对我们的生活是必不可少的，特别是在转化方面 生物分子从一种形式转变为另一种形式。然而，在新陈代谢活动较高的区域，如大脑， 铜资源管理不善被认为是导致意外结合铜的原因，这种结合铜与 氧气形成活性氧物种(ROS)，导致重要的氧化降解失控 生物分子，最终导致衰弱的神经疾病。定义连接环境 而外来结合铜能够产生ROS的机制是我们的首要目标。 因为铜是生物中所有氧化还原活性金属中最不稳定的，定义了导致这种 ROS具有挑战性。铜与氧气在高度可控配位下的反应机理 环境，如蛋白质或小的铜络合物，提供了一个逻辑起点来定义什么是 化学上可能的，或者如果不是，在定义较少、管理不善的条件下化学上可能的。我们 假设对氧气活化和氧化反应的机械理解将有助于 最好是减少管理不善的铜矿的ROS生产。更具体地说，双核铜位 活化氧气和氧化困难的底物将进行深入的研究。我们使用一种综合的方法在我们的 具有忠实结构关系的结构相关的低分子络合物的研究 在小分子细节水平上检查生物部位的氧化反应，以揭示内在的 结构、电子和性能。由于我们的工作缺乏生物系统的上层建筑，我们使用 极低的溶液温度进行调查。运营的前提是这样的综合体 将为氧化(铜(I)O2)和还原(铜-O2底物)的一半提供重要的机理见解。 生物系统的反应，如果适当注意产生适当的铜配位 环境。

Project Summary: Copper enzymes that react with dioxygen are essential to our lives especially with respect to transforming biological molecules from one form to another. Yet, in areas of high metabolic activity such as the brain, mismanagement of copper resources is thought to lead to adventitiously bonded copper that reacts with dioxygen to form reactive dioxygen species (ROS) that lead to uncontrolled oxidative degradation of important biological molecules, ultimately leading to debilitating neurological diseases. Defining the ligation environment and the mechanism by which adventitiously bonded copper is able to create ROS is our overarching objective. As copper is the most labile of all redox active metals in biology, defining the coordination that leads to such ROS is challenging. Mechanisms of the reaction of copper with dioxygen in highly controlled coordination environments, such as proteins or in small copper complexes, provide a logical starting point to define what is chemically possible or if not what is chemically probable under less-defined, mismanaged conditions. We postulate that a mechanistic understanding of dioxygen activation and oxidative reactivity will inform on how best to attenuate ROS production at mismanaged copper sites. More specifically, binuclear copper sites that activate O2 and oxidize difficult substrates will be investigated in depth. We use a synthetic approach in our research whereby structurally-related low molecular weight complexes having faithful structural relationships to biological sites are examine for their oxidative reactive at a small molecule level of detail to reveal intrinsic structural, electronic, and properties. As our work lacks the superstructure of the biological systems, we use extremely low solution temperature to perform the investigation. The operating premise is that such complexes will provide important mechanistic insights to the oxidative (Cu(I) + O2) and reductive (Cu-O2 + substrate) half- reactions of biological systems if appropriate attention is directed to creating appropriate copper ligation environments.