Multimetallic Catalysis in Biology and Synthesis

生物学和合成中的多金属催化

• 批准号: 10402390
• 负责人: Neal P Mankad
• 金额: $ 38.83万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10402390
• 关键词: Active Sites; Area; Biology; Carbon Dioxide; Carbon monoxide dehydrogenase; Catalysis; Chemicals; Complex; Drug Industry; Geometry; Health; Human; Knowledge; Laboratories; Maps; Metals; Methods; Mononuclear; Nitrous Oxide; Organic Chemistry; Pattern; Pharmacologic Substance; Planet Earth; Reaction; Regulation; Research; Study models; System; Technology; Work; base; catalyst; chemical synthesis; design; greenhouse gases; improved; metalloenzyme; nitrous oxide reductase; small molecule; tool

The proposed work focuses on (a) understanding how natural multimetallic clusters operate as active sites in metalloenzymes, and (b) using synthetic multimetallic clusters for productive chemical synthesis. Many metalloenzymes feature multimetallic clusters as active sites for catalyzing multielectron/multiproton transformations of gaseous small molecules, including cases of environmental significance to human health like atmospheric regulation of carbon dioxide and nitrous oxide. In many cases, these multimetallic clusters have unusual compositions and geometries, and so the chemical reactivity patterns have not been mapped out in laboratory settings. This proposal aims to achieve that for several multimetallic active sites, including the tetrametallic active site of nitrous oxide reductase and the heterobimetallic active site of carbon monoxide dehydrogenase, using synthetic model studies based on the PI’s established expertise in this area. Additionally, lessons about how these natural multimetallic clusters operate will be applied to develop synthetic multimetallic catalysts for C-C and C-X bond-forming reactions of relevance to pharmaceutical synthesis. The benefits of developing this catalytic paradigm for synthetic organic chemistry include emergence of reactivity and selectivity patterns that are complementary to established mononuclear catalyst systems, as well as the advancement of a bio-inspired tool to design earth-abundant metal catalysts that improve the sustainability of synthetic technologies in the pharmaceutical industry.

拟议的工作重点是（a）了解自然多元金属群集的运作方式 金属酶中的活性位点，以及（b）使用合成多金属簇作为产品 化学合成。许多金属酶以多金属簇为活性位点 催化气态小分子的多电体/多元子转化，包括 对人类健康具有重要意义的案例，例如碳的大气调节 二氧化物和一氧化二氮。在许多情况下，这些多色群集具有不寻常的 组成和几何形状，因此尚未映射化学反应性模式 在实验室环境中。该建议旨在为几个多功能活动实现这一目标 位置，包括一氧化二氮还原和异金属金属的位点 一氧化碳脱氢酶的活性位点，使用基于PI的合成模型研究 在该领域建立了专业知识。此外，关于这些天然多属金属如何的课程 簇运行将用于开发用于C-C和C-X的合成多金属催化剂 与药物合成相关的键形反应。发展的好处 这种用于合成有机化学的催化范例包括反应性紧急和 已建立的单核催化剂系统完整的选择性模式， 以及以生物风格的工具的发展来设计地球丰富的金属催化剂 提高制药行业合成技术的可持续性。