Low-Coordinate Synthetic Models for Iron-Sulfur Enzymes

项目摘要 酶对N2和CO2进行惊人的多电子还原，对于这些具有挑战性的反应， 使用铁硫簇。N2还原（固氮酶）和CO2还原活性中心的铁硫簇 (FeNi CO脱氢酶）具有独特的形状，被认为在两个 相邻金属两种金属的协同反应性可能是减少这些小分子的关键， 我们还不知道这些金属是如何一起工作的，它们是如何将电子和质子引导到 底物，以及它们如何在温和条件下介导键重排。直接研究每种酶 已经导致了该机制的工作模型，但中间体的蛋白质晶体结构方面， 有时候会混淆和抵触无机化学原理。使磁场向前移动需要新的铁 这些化合物证明了对于这些簇预期的合理行为。 我们的指导假设是，合成的铁硫“模型”化合物可以揭示可行的几何形状 和原子簇中间体的光谱特征。因为合成化合物具有已知的结构， 它们使我们能够将光谱特征与特定的结构特征相关联。更重要的是可以 用于测试机械步骤和途径的可行性。综合模型策略将用于 铁硫和铁硫镍化合物，包含固氮酶中活性位点簇的关键方面 和CO脱氢酶。 利用我们在铁和镍的有机金属化学方面的长期经验，我们使用创新的 基于大体积支持配体的合成方法。这些配体保护活性位点，以使得能够结合 气态底物和质子耦合电子转移促进底物还原，而不积累 消费标准.在固氮酶建模中，我们将测试一种新的机制，其中预组织的多金属铁/硫 在这种环境下，质子耦合电子快速转移到N2，迅速将N2转化为二氮烯（N2 H2）。 这一目标的成功将揭示固氮酶在温和条件下捕获通常不反应的N2分子的方式。 条件下，使用质子和电子运动的耦合。在CODHase建模中，我们将准备并 研究了第一个具有三配位镍位点的铁硫簇合物，它对铁硫簇合物具有很大的结构保真度。 酶的活性位点。我们将通过实验评估它们的氧化还原化学、光谱和反应性 与CO2和其他化合物，以测试在酶中提出的机制的可行性。 通过研究与这两种铁硫酶相关的化学，我们将获得关于以下方面的普遍知识： 如何氢键，质子耦合电子转移，硫供体，电子迁移，多金属 协同性使生物系统能够处理小分子。此外，这种理解有助于 未来化学家减少N2和CO2用于能源科学的能力。

Project Summary Enzymes perform amazing multielectron reductions of N2 and CO2, and for these challenging reactions they use iron-sulfur clusters. The iron-sulfur clusters in the active sites of N2-reducing (nitrogenase) and CO2-reducing (FeNi CO dehydrogenase) enzymes have unique shapes that are thought to generate binding sites on two adjacent metals. The cooperative reactivity of two metals may be the key to reducing these small molecules, but we do not yet understand how these metals work together, how they channel electrons and protons to the substrates, and how they mediate bond rearrangements under mild conditions. Direct studies on each enzyme have led to working models of the mechanism, but aspects of the protein crystal structures of intermediates are confusing and sometimes contradict inorganic chemistry principles. Moving the field forward requires new iron compounds that demonstrate what is reasonable behavior expected for these clusters. Our guiding hypothesis is that synthetic iron-sulfur "model" compounds can reveal the feasible geometries and spectroscopic signatures of cluster intermediates. Because the synthetic compounds have known structures, they enable us to correlate spectroscopic signatures with specific structural features. More importantly, they can be used to test the feasibility of mechanistic steps and pathways. The synthetic model strategy will be used for iron-sulfur and iron-sulfur-nickel compounds that contain key aspects of the active-site clusters in the nitrogenase and CO dehydrogenase enzymes. Taking advantage of our long experience in the organometallic chemistry of iron and nickel, we use innovative synthetic approaches based on bulky supporting ligands. These ligands protect active sites to enable binding of the gaseous substrates, and proton-coupled electron transfer facilitates substrate reduction without buildup of charge. In nitrogenase modeling, we will test a new mechanism where a preorganized multimetallic iron/sulfur environment enables rapid proton-coupled electron transfer to N2, rapidly converting the N2 to diazene (N2H2). Success in this aim would reveal the way that nitrogenase traps the normally unreactive N2 molecule under mild conditions, using the coupling of proton and electron movement. In CODHase modeling, we will prepare and study the first iron-sulfur clusters with three-coordinate nickel sites, which have great structural fidelity to the proposed enzyme active site. We will experimentally evaluate their redox chemistry, spectroscopy, and reactivity with CO2 and other compounds, in order to test the feasibility of mechanisms proposed in the enzyme. By studying chemistry relevant to both these iron-sulfur enzymes, we will gain generalizable knowledge about how hydrogen bonding, proton-coupled electron transfer, sulfur donors, electron migration, and multimetallic cooperativity enable biological systems to process small molecules. Further, this understanding contributes to the future ability of chemists to reduce N2 and CO2 for use in energy science.