Low-Coordinate Synthetic Models for Iron-Sulfur Enzymes

项目摘要 酶对氮气和二氧化碳进行惊人的多电子还原，对于这些具有挑战性的反应，它们 使用铁硫团簇。氮气还原(固氮酶)和二氧化碳还原活性中心的铁硫团簇 (FeNi CO脱氢酶)酶具有独特的形状，被认为在两个 相邻的金属。两种金属的协同反应性可能是减少这些小分子的关键，但 我们还不知道这些金属是如何协同工作的，它们是如何将电子和质子输送到 底物，以及它们如何在温和的条件下调解键重排。对每种酶的直接研究 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是 令人困惑，有时甚至与无机化学原理相矛盾。推动这一领域向前发展需要新的铁 展示这些团簇预期的合理行为的化合物。 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构型。 以及簇合物中间体的光谱特征。因为合成的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联系起来。更重要的是，他们可以 用于测试机械化步骤和路径的可行性。综合模型策略将用于 铁-硫和铁-硫-镍化合物，包含固氮酶活性中心簇的关键方面 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其能够结合 气态衬底和质子耦合电子转移有助于衬底还原，而不会积聚 充电。在固氮酶模拟中，我们将测试一种新的机制，在该机制中，预先组织的多金属铁/硫 环境使质子耦合电子快速转移到氮气，迅速将氮气转化为双氮烯(N2H2)。 这一目标的成功将揭示固氮酶在温和的条件下捕获通常不反应的氮气分子的方式 条件，利用质子和电子运动的耦合。在CODHase建模中，我们将准备和 研究了第一个具有三配位镍中心的铁硫团簇，它们的结构保真度很高 建议的酶活性部位。我们将从实验上评估它们的氧化还原化学、光谱和反应活性。 以CO2等化合物为实验材料，验证提出的酶作用机制的可行性。 通过研究与这两种铁硫酶相关的化学，我们将获得关于 氢键、质子耦合电子转移、硫供体、电子迁移和多金属 协作性使生物系统能够处理小分子。此外，这一理解有助于 化学家未来减少氮气和二氧化碳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.