Multimetallic Catalysis in Biology and Synthesis

拟议的工作重点是（a）了解天然多金属簇如何作为 金属酶中的活性位点，和（B）使用合成的多金属簇用于生产 化学合成许多金属酶以多金属簇为活性位点， 催化气体小分子的多电子/多质子转化，包括 对人类健康具有环境意义的案例，如大气碳调节 二氧化碳和一氧化二氮在许多情况下，这些多金属簇具有不寻常的 组成和几何形状，因此化学反应模式尚未绘制 在实验室环境中。该建议旨在实现几种多金属活性 位点，包括一氧化二氮还原酶的四金属活性位点和 一氧化碳脱氢酶的活性位点，使用基于PI的合成模型研究 在这方面的专业知识。此外，关于这些天然多金属 集群操作将用于开发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的出现， 选择性模式与已建立的单核催化剂体系互补， 以及生物启发工具的进步，以设计地球上丰富的金属催化剂， 提高制药工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.