DIOXYGEN ACTIVATION BY MODEL COPPER COMPLEXES

模型铜络合物的二氧活化

• 批准号: 2444842
• 负责人: T DANIEL STACK
• 金额: $ 10.04万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2444842
• 关键词: L ascorbate oxidase; Raman spectrometry; X ray crystallography; active sites; benzene; chemical binding; chemical kinetics; chemical stability; chemical synthesis; copper; diamines; electrochemistry; enzyme activity; hydrogen peroxide; ligands; metal complex; nitric oxide; nitrites; nuclear magnetic resonance spectroscopy; oxidation reduction reaction; oxidoreductase; oxygen; synthetic enzyme

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.

在此描述的研究的广泛和长期目标 应用是阐明结构，电子和化学的 含金属的铜酶的特性 可逆地绑定和/或激活二氧化物或二氧化物类似物（一氮 氧化物）。该方法是合成模拟方法的方法 金属分子的活性位点，低分子量 复合物在小分子水平的小分子水平上进行了检查 细节。因此，所揭示的特性是金属络合物的固有的 与蛋白质基质的影响未耦合。拟议的研究 最终是针对集会和表征的 三核铜簇模仿 在蓝色氧化酶中发现的三核铜簇，这是负责的 将二氧化物还原为水。激活的机制是 与双核铜中心的截然不同 尽管存在结构相似性，但酪氨酸酶或血红蛋白蛋白。一个完整的 理解合成，三聚铜的双氧反应性 复合物将有助于阐明一些现有的结构差异 在晶体学和光谱学之间。该分析将需要研究 的不仅是三核中心，而且相关的单体和 二聚体铜配合物。配体设计和合成是不可或缺的部分 这项研究；具有具有的合成配体系统的开发 必要的灵活性以适应不同的几何偏好 Cu-ii和Cu-i的虽然仍保持易感性组织，但 该提案的必要目标。提议的具体目的 研究如下：（i）MU-ETA2的表征：ETA2CU2-O2-L2 低温下具有简单单体配体的铜配合物 定义最小几何和电子约束所必需的 二氧化物结合和激活； （ii）稳定合成 四面体cu-ii物种在面部封盖，三脂配体中 提供明确定义的光谱示例，可以用作 光谱基准； （iii）表征和稳定 一氧化氮和亚硝酸盐与四面体Cu-II的反应中间体 和Cu-i复合物，目的是产生与 亚硝酸盐还原酶的催化循环； （iv）发展模块化 配体组装的合成方法合成三核 铜簇旨在稳定铜/二氧化物中间体； （v） 合成三核铜簇的组装在结构上与 用三核配体和 它们与二氧化物的反应性的表征。