Multimetallic Catalysis in Biology and Synthesis

拟议的工作重点是：(A)了解天然多金属簇合物如何作为 金属酶中的活性部位，以及(B)使用合成的多金属簇合物用于生产 化学合成。许多金属酶以多金属簇为活性中心 催化气态小分子的多电子/多质子转化，包括 对人类健康具有环境意义的案例，如大气中碳的调节 二氧化碳和一氧化二氮。在许多情况下，这些多金属团簇具有不同寻常的 组成和几何结构，所以化学反应模式还没有被绘制出来 在实验室的环境中。本提案旨在为几种多金属活性物质实现这一目标 活性中心，包括一氧化二氮还原酶的四金属活性中心和杂双金属 用基于PI的合成模型研究一氧化碳脱氢酶的活性部位 在这一领域已有成熟的专业知识。此外，关于这些天然多金属如何 团簇操作将应用于开发用于C-C和C-X的合成多金属催化剂 与药物合成相关的成键反应。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和 与已建立的单核催化剂体系互补的选择性模式，如 以及一种生物启发工具的进步，以设计富含地球的金属催化剂 提高制药行业合成技术的可持续性。

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.