Synthetic Modeling of Copper Protein Active Sites

描述（由申请人提供）：在其活性位点含有铜离子的蛋白质代表了一类在广泛的生命过程中发挥重要作用的功能重要的金属生物分子。铜蛋白的功能多样性是匹配的活性位点的几何，电子结构和光谱特征的变化。一个分子水平的结构/功能关系的理解是可取的，但尽管广泛的研究工作，许多问题仍未解决的详细机制的行动和铜蛋白活性位点的化学。拟议研究的目的是获得铜蛋白质结构和功能的基本化学见解，并通过合成建模方法开发新的和根本上重要的铜化学，其中设计用于复制金属蛋白活性位点特性的低分子量复合物的特征和它们的反应性研究。本研究的具体目的是：1。理解在许多金属蛋白中发现的1型铜电子转移位点的可变结构和氧化还原行为的相互关系。铜-硫醇盐络合物的性质和钌和/或钌/铜-硫醇盐组件的电子转移动力学的扰动将被检查。2.通过研究受阻双齿N-供体配体、酚盐螯合物和具有连接的远程氧化剂的配体的O2反应性，获得对生物重要蛋白质（如多巴胺β-单加氧酶和半乳糖氧化酶）中单铜位点的双氧活化的基本见解。3.调查dioxgyen激活的三铜活性位点的普遍存在的和具有生物意义的多铜氧化酶通过使用一种新的逐步合成策略，涉及1：1的Cu/O2物种与双铜配合物的反应。4.了解一氧化二氮还原酶的新型（多硫基）四铜活性位点的基本化学，这是全球氮循环的重要参与者。平行的研究将进行各种单和二硫桥的双铜配合物和专门设计的四铜集群。

DESCRIPTION (provided by applicant): Proteins that contain copper ions in their active sites represent a large and functionally significant class of metallobiomolecules that play important roles in a wide range of life processes. The functional diversity of copper proteins is matched by variability in active site geometric, electronic structural, and spectroscopic features. A molecular level understanding of structure/function relationships is desirable, but despite extensive research efforts many issues remain unresolved regarding the detailed mechanisms of action and underlying chemistry of copper protein active sites. The aim of the proposed research is to obtain essential chemical insights into copper protein structure and function and to develop novel and fundamentally significant copper chemistry through the synthetic modeling approach, wherein low molecular weight complexes designed to replicate metalloprotein active site properties are characterized and their reactivity studied. The specific aims of the proposed research are to: 1. Understand the interrelationships of the variable structures and redox behaviors of type 1 copper electron transfer sites found in numerous metalloproteins. Perturbations of copper-thiolate complex properties and electron transfer kinetics of ruthenium and/or rhenium/copper-thiolate assemblies will be examined. 2. Obtain fundamental insight into dioxygen activation by monocopper sites in biologically important proteins such as dopamine beta-monooxygenase and galactose oxidase through studies of the O2 reactivity of copper complexes of hindered bidentate N-donor ligands, phenolate chelates, and ligands with attached remote oxidants like those operative in catalysis by copper enzymes. 3. Investigate dioxgyen activation by the tricopper active sites of the ubiquitous and biologically significant multicopper oxidases by using a novel stepwise synthetic strategy involving the reaction of 1:1 Cu/O2 species with dicopper complexes. 4. Understand the underlying chemistry of the novel (mu-sulfido)tetracopper active site of nitrous oxide reductase, an important participant in the global nitrogen cycle. Parallel studies will be performed of various mono- and disulfido-bridged dicopper complexes and of specifically designed tetracopper clusters.