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 过渡金属复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， 从脂肪酸通过脂氧合酶氧化到氧气的进化 照片系统II。这些金属酶和相关系统中有许多具有 已经详细研究了，但是对 它们的基本化学反应性是它们的基础。通过研究一系列 模型化合物和模型反应，一种基本和预测 正在发展理解。 涉及氢原子转移的反应是 描述的研究。利率常数与 热力学驱动力将扩展到新系统，并使用 包括苯酚在内的更广泛的底物。驾驶以外的其他因素 将探测力。有机自由基化学和马库斯都 电子传递理论将用于提供见解。想法 氢汤姆转移反应的发展范式的基础 将应用于其他氧化机制，尤其是氢化物 转移过程。 拟议的工作包括机械和合成研究。 氧化协调复合物或铁，锰，库珀和 将准备钌，并检查其反应。这些复合物 是用于氧化酶的功能模型，例如脂氧合酶和 多巴胺β-单加氧酶。通过研究烃的氧化， 苯酚和其他底物与氧化还原的测量并行 潜力，PK/A值和自汇率，我们将生成一个 了解这些反应，更广泛地了解金属如何介导 生化系统中质子和电子的耦合运动 关联。