DIOXYGEN ACTIVATION BY MODEL COPPER COMPLEXES

本文所述研究的广泛和长期目标 应用是阐明结构，电子和化学 铜酶的含金属配位位点的性质， 可逆地结合和/或激活双氧或双氧类似物（硝酸 氧化物）。该方法是合成类似物的方法， 金属生物分子的活性位点， 合成复合物，并在小分子水平上进行检测， 详细因此，所揭示的性质是金属络合物所固有的 从蛋白质基质的影响中解偶联。拟议研究 最终是针对组装和表征 三核铜簇合物，模拟的结构和反应性的 在蓝色氧化酶中发现的三核铜簇， 用于将分子氧还原成水。激活机制是 与双核铜中心的结构有很大不同， 酪氨酸酶或血蓝蛋白，尽管存在结构相似性。全 理解合成三聚铜的分子氧反应性 复合体将有助于澄清一些现有的结构性差异 晶体学和光谱学之间的联系这一分析将需要研究 的，不仅是三核中心，但也有相关的单体和 二聚铜配合物。配体的设计和合成是一个不可或缺的部分 这项研究;开发合成配体系统， 必要的灵活性，以适应不同的几何偏好 Cu-II和Cu-I，虽然仍然保持着一个倾向性的组织， 这是该提案的一个必要目标。建议的具体目标 研究内容如下：（i）mu-eta_2：eta_2Cu_2-O_2-L_2的表征 铜络合物与简单的单体配体在低温下， 定义所需的最小几何和电子约束， 分子氧结合和活化;（ii）合成的， 四面体Cu-II物种在面部盖帽，三氮配体， 提供了定义明确的光谱学实例， 光谱基准;（三）表征和稳定的 一氧化氮和亚硝酸盐与四面体Cu-II的反应中间体 和Cu-I络合物，目的是产生与以下物质相关的物质： 亚硝酸盐还原酶的催化循环;（iv）模块化的开发 合成三核配体的合成方法 设计用于稳定铜/分子氧中间体的铜簇;（v） 组装合成的三核铜簇合物， 在具有三核配体的抗坏血酸氧化酶中观察到， 表征它们与分子氧的反应性。

The broad and long term objective of the research described in this application is the elucidation of the structural, electronic, and chemical properties of metal-containing coordination sites of copper enzymes that reversibly bind and/or activate dioxygen or dioxygen analogs (nitric oxide). The methodology is that of the synthetic analog approach to the active sites of metallobiomolecules, whereby low molecular weight complexes are synthesized and examined at a small molecule level of detail. The properties revealed are thus intrinsic to the metal complex uncoupled from the influences of the protein matrix. The proposed research is ultimately directed towards the assembly and characterization of trinuclear copper clusters that mimic the structure and reactivity of the trinuclear copper clusters found in blue oxidases, which are responsible for reduction of dioxygen to water. The mechanism of activation is dramatically different from that of the dinuclear copper centers of tyrosinases or hemocyanins, though a structural similarity exists. A full understanding of the dioxygen reactivity of synthetic, trimeric copper complexes will help clarify some of the existing structural disparities between crystallography and spectroscopy. This analysis will require study of, not only the trinuclear centers, but also the related monomeric and dimeric copper complexes. Ligand design and synthesis is an integral part of this research; development of synthetic ligand systems which have the requisite flexibility to accommodate the different geometric preferences of Cu-II and Cu-I, while still maintaining a predisposed organization, is a necessary goal of this proposal. The specific aims of the proposed research are as follows: (i) characterization of mu-eta2:eta2Cu2-O2-L2 copper complexes with simple monomeric ligands at low temperatures to define the minimum geometric and electronic constraints necessary for dioxygen binding and activation; (ii) stabilization of a synthetic, tetrahedral Cu-II species in a facial capping, trinitrogen ligand to provide well defined spectroscopic examples that can be used as spectroscopic benchmarks; (iii) characterization and stabilization of the reaction intermediates of nitric oxide and nitrite with tetrahedral Cu-II and Cu-I complexes with the intention of generating species relevant to the catalytic cycle of nitrite reductase; (iv) development of a modular synthetic approach to ligand assembly for the synthesis of trinuclear copper clusters designed to stabilize copper/dioxygen intermediates; (v) assembly of synthetic trinuclear copper clusters structurally similar to that observed in ascorbate oxidase with trinuclear ligands and characterization of their reactivity with dioxygen.