Structure/Function Correlations Over Copper Enzymes

项目摘要 自然界中，铜(和铁)酶在氧气活化中起主导作用。它们在黑色素生成过程中很重要， 神经化学、金属离子代谢、质子泵、生物修复、ROS生成、一系列疾病 可用于植入式设备的生物燃料电池。在分子水平上，它们可以通过 1，2，可能是3个和4个电子来完成一系列功能，包括从这两个弱原子中提取氢原子 和强的C-H键，2和1个铜中心的亲电活化，以及O2还原到 水到铁的代谢通过多铜氧化酶和质子泵通过血红素-铜氧化酶。氧气- 激活铜酶根据结构和与单核的反应类型分为五类 根据铜和氧的氧化还原活化态进一步划分了铜的类别。我们的研究使用了 结合酶的动力学以获得中间体，应用广泛的光谱分析 定义这些平行模型研究以及这些动力学、光谱和模型结果的耦合 电子结构计算确定前线分子轨道和反应坐标的研究 催化作用。这项研究工作的创新方面包括开发新的光谱方法， 铜/氧中间体常表现出的独特光谱特征的几何和光谱分析 电子结构和这些数据与电子结构计算的耦合 经过实验验证的反应坐标。这些研究确定了每一类的反应机理和 分子水平上的子类(在药物、设备和催化剂的设计中很重要)和平行研究 通过这些课程，我们对自然界中氧气利用的结构/功能相关性有了全面的了解。

Project Summary Cu (along with Fe) enzymes play dominant roles in O2 activation in Nature. They are important in melanogenesis, neurochemistry, metal ion metabolism, proton pumping, bioremediation, ROS generation, a range of disease states, and can be utilized in biofuel cells for implantable devices. On a molecular level these can reduce O2 by 1,2, possibly 3 and 4 electrons to accomplish a range of functions, including H-atom abstraction from both weak and strong C-H bonds, electrophilic activation by 2 as well as 1 Cu center, and the coupling of O2 reduction to water to Fe metabolism by the multicopper oxidases and proton pumping by the heme-copper oxidases. Oxygen- activating Cu enzymes are divided into five classes based on structure and type of reaction with the mononuclear Cu class further divided based on the redox active states of the Cu and the oxygen. Our studies use the combination of kinetics on the enzymes to obtain intermediates, application of a wide range of spectroscopies to define these, parallel model studies and the coupling of the results of these kinetic, spectroscopic and model studies to electronic structure calculations to define frontier molecular orbitals and reaction coordinates in catalysis. Innovative aspects of this research effort include the development of new spectroscopic methods, the analyses of the unique spectral features often exhibited by Cu/O2 intermediates in terms of their geometric and electronic structures and the coupling of these data to electronic structure calculations for development of experimentally validated reaction coordinates. These studies define the reaction mechanisms of each class and subclass on a molecular level (important in the design of drugs, devices and catalysts) and by parallel studies over the classes develop general insight into structure/function correlations over oxygen utilization in Nature.