Multimetallic Catalysis in Biology and Synthesis

生物学和合成中的多金属催化

基本信息

批准号：
10624252
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
项目类别：
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

项目摘要

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）了解天然多金属簇如何作为金属酶中的活性位点，以及（b）使用合成多金属簇进行生产许多金属酶以多金属簇作为活性位点。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重要性的案例，例如大气碳调节在许多情况下，这些多金属簇具有不寻常的特征。成分和几何形状，因此化学反应模式尚未绘制该提案旨在实现几种多金属活性物质的这一目标。位点，包括一氧化二氮还原酶的四金属活性位点和异双金属活性位点一氧化碳脱氢酶的活性位点，使用基于 PI 的合成模型研究此外，还提供了有关如何使用这些天然多金属的经验教训。集群运作将用于开发C-C和C-X合成多金属催化剂与药物合成相关的成键反应开发的好处。这种合成有机化学的催化范式包括反应性的出现和选择性模式是对已建立的单核催化剂系统的补充，例如以及用于设计地球丰富的金属催化剂的仿生工具的进步提高制药行业合成技术的可持续性。