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金属生物分子的一个大而功能重要的类别，在广泛的生命过程中起着重要作用。铜蛋白的功能多样性与活性位点几何、电子结构和光谱特征的可变性相匹配。对结构/功能关系的分子水平理解是必要的，但尽管进行了广泛的研究，但关于铜蛋白活性位点的详细作用机制和潜在化学性质，许多问题仍未解决。本研究的目的是获得铜蛋白结构和功能的基本化学见解，并通过合成建模方法开发新颖且具有根本意义的铜化学，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进行表征并研究其反应性。提出的研究的具体目的是：1。了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。铜硫酸盐配合物的性质和钌和/或铼/铜硫酸盐组合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、酚酸盐螯合物和带有远端氧化剂的配体（如铜酶催化作用的配体）的铜配合物的氧反应活性，获得对多巴胺-单氧酶和半乳糖氧化酶等重要生物蛋白中单铜位点的双氧活化的基本见解。3. 采用一种新型的分步合成策略，利用Cu/O2与二铜配合物的1:1反应，研究了普遍存在的具有重要生物学意义的多铜氧化酶的三铜活性位点对二氧的激活作用。4. 了解一氧化二氮还原酶的新型（mu-sulfido）四铜活性位点的潜在化学成分，这是全球氮循环的重要参与者。平行研究将进行各种单和二硫桥接二铜配合物和专门设计的四铜簇。

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.