UNDERSTANDING METAL MEDIATED C-H AND O-H BOND OXIDATIONS

了解金属介导的 C-H 和 O-H 键氧化

• 批准号: 6363262
• 负责人: JAMES M MAYER
• 金额: $ 26.06万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-02-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6363262
• 关键词: X ray crystallography; active sites; chemical synthesis; chemical transfer reaction; covalent bond; electron spin resonance spectroscopy; enzyme activity; enzyme mechanism; heavy metals; hydrocarbons; hydrogen; hydroxyl group; metal complex; metalloenzyme; nicotinamide adenine dinucleotide; nuclear magnetic resonance spectroscopy; oxidation

The proposed research will provide fundamental understanding of how transition metal complexes and active sites oxidize C-H and O-H bonds. Such chemical processes occur in a wide range of biological systems, from fatty acid oxidations by lipoxygenases to oxygen evolution by photo-system II. Many of these metalloenzymes and related systems have been individually studied in detail, but there is limited knowledge of their basic chemical reactivity underlies them. By studying a range of model compounds and model reactions, a fundamental and predictive understanding is being developed. Reactions that involve transfer of a hydrogen atom are a major focus of the studies described. The correlations of rate constants with thermodynamic driving force will be extended to new systems and with a wider range of substrates, including phenols. Factors other than driving force will be probed. Both organic radical chemistry and the Marcus theory of electron transfer will be used to provide insights. The ideas underlying this developing paradigm for hydrogen tom transfer reactions will be applied to other oxidation mechanisms, especially hydride transfer processes. The proposed work includes both mechanistic and synthetic studies. Oxidizing coordination complexes or iron, manganese, cooper, and ruthenium will be prepared and their reactions examined. These complexes are functional models for oxidizing enzymes such as lipoxygenase and dopamine beta-monooxygenase. By studying the oxidations of hydrocarbons, phenols, and other substrates in parallel with measurements of redox potentials, pK/a values, and self exchange rates, we will generate an understanding these reactions and, more generally, how metals mediate the coupled movement of protons and electrons in systems of biochemical relevance.

拟议的研究将提供对如何 过渡金属络合物和活性位点氧化C-H和O-H键。 这种化学过程发生在广泛的生物系统中， 从脂氧合酶的脂肪酸氧化到氧气的析出 照相系统 II.许多这些金属酶和相关系统已经 详细研究过，但了解有限 它们的基本化学反应是它们的基础。通过研究一系列 模型化合物和模型反应，基本的和预测的 理解正在发展。 涉及氢原子转移的反应是一个主要焦点 研究描述。速率常数与的相关性 热力学驱动力将扩展到新系统并具有 更广泛的底物，包括酚类。驾驶以外的因素 力将被探测。有机自由基化学和马库斯化学 电子转移理论将用于提供见解。想法 氢原子转移反应的发展范例的基础 将应用于其他氧化机制，特别是氢化物 转移过程。 拟议的工作包括机械研究和综合研究。 氧化配位络合物或铁、锰、铜和 将制备钌并检查它们的反应。这些复合体 是氧化酶（例如脂氧合酶）的功能模型 多巴胺β-单加氧酶。通过研究碳氢化合物的氧化， 酚类和其他底物与氧化还原测量并行 势、pK/a 值和自汇率，我们将生成 了解这些反应，更一般地说，了解金属如何介导 生化系统中质子和电子的耦合运动 关联。