Structure/Function Correlations Over Copper Enzymes

项目摘要 Cu（沿着Fe）酶在自然界中的O2活化中起主导作用。它们在黑素生成中很重要， 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 状态，并且可以用于可植入设备的生物燃料电池中。在分子水平上，它们可以通过以下方式减少O2： 1，2，可能3和4个电子，以完成一系列功能，包括H原子的抽象，从两个弱 和强C-H键，2和1 Cu中心的亲电活化，以及O2还原与 通过多铜氧化酶和血红素-铜氧化酶的质子泵将水代谢为铁。氧气- 活化铜酶根据结构和与单核细胞反应的类型分为五类。 Cu类根据Cu和氧的氧化还原活性状态进一步划分。我们的研究使用 结合酶的动力学以获得中间体，应用广泛的光谱学， 定义这些，平行模型研究和这些动力学，光谱和模型结果的耦合 研究电子结构计算，以确定前线分子轨道和反应坐标， 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， 分析了Cu/O2中间体在几何和光谱上经常表现出的独特光谱特征， 电子结构和耦合这些数据的电子结构计算的发展 实验验证的反应坐标。这些研究定义了每类的反应机制， 分子水平上的亚类（在药物，设备和催化剂的设计中很重要）和平行研究 在课程中，发展了对自然界中氧利用的结构/功能相关性的一般认识。

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.