Bioorganometallic Iron-Sulfide Assemblies Related to Hydrogenases

描述（申请人提供）：该项目重点研究称为氢化酶的酶的作用机制，其中有两种，[NiFe]-和[FeFe]-氢化酶，反映了活性位点的金属。这些酶是人类肠道中许多病原体的H2依赖性代谢的基础，作用于两种底物质子（H+）和H2。已知几个相关的酶家族。这些结果进一步与基础催化剂技术相关。本工作旨在阐明[NiFe]-氢化酶的Ni-C、Ni-SI、Ni-R和Ni-L态以及[FeFe]-氢化酶的Hred态的结构和反应性。特别注意的是针对的位置和行为H2衍生的底物，通常是不可见的蛋白质光谱学和蛋白质晶体学检测不到。这些酶的活性位点是非常不寻常的，具有几个独特的辅因子，如CO，氰化物，并在[FeFe]的情况下，氨基二硫醇。这项工作采用有机金属化学的工具来制作活性位点的模型（复制品）。将通过NMR光谱和X-射线晶体学检查分子水平的洞察力的氢配体的行为，注意立体化学，氧化还原电位，酸碱行为和动力学性质。第一个主题探讨方法稳定nickelIII，N-C状态的特征，使用有机金属配体，模仿硫醇配体的供体性质。第二个主题探讨的氰化物辅因子绑定到铁的作用，注意开发工具来修改这些群体的行为。这一目标建立在硼试剂能够仿生激活铁氰化物中的氢的初步证据的基础上。第三个主题，主要关注[FeFe]酶，阐明了导致双向性的因素，即模型产生和氧化H2的能力。最后一个主题，这也强调[FeFe]-氢化酶，检查假说，试图解释不寻常的结构功能的酶的还原状态。这一主题将导致新的配体支架，稳定终端氢化物配体。

DESCRIPTION (provided by applicant): The project focuses on the mechanisms of action of enzymes called hydrogenases, of which there are two, [NiFe]- and the [FeFe]-hydrogenases, reflecting the metals at the active sites. These enzymes, which underpin H2-dependent metabolism of many pathogens in the human gut, act on two substrates protons (H+) and H2. Several related families of enzymes are known. The results are further relevant to fundamental catalyst technology. The work aims to clarify the structure and reactivity of the Ni-C, Ni-SI, Ni-R and Ni-L states of the [NiFe]-hydrogenases and the Hred state of the [FeFe]-hydrogenases. Special attention is directed at the location and behavior H2-derived substrates that are usually invisible to protein spectroscopy and are undetectable by protein crystallography. The active sites of these enzymes are highly unusual, featuring several distinctive cofactors, such as CO, cyanide, and, in the [FeFe] case, an aminodithiolate. The work employs the tools of organometallic chemistry to produce models (replicas) of the active sites. Molecular-level insights into behavior of the hydrogenic ligands will be examined by NMR spectroscopy and X-ray crystallography with attention to stereochemistry, redox potentials, acid-base behavior, and kinetic properties. The first theme examines methods for stabilizing nickelIII, characteristic of N-C state, using organometallic ligands that emulate the donor properties of thiolate ligands. The second theme examines the role of the cyanide cofactors bound to Fe, with attention to developing tools to modify the behavior of these groups. This aim builds on preliminary evidence that boron reagents enable biomimetic activation of hydrogen in iron cyanides. The third theme, with a primary focus on the [FeFe] enzymes, elucidates the factors that lead to bidirectionality, the ability of models to both produce and oxidized H2. The last theme, which also emphasizes [FeFe]-hydrogenase, examines hypotheses that seek to explain the unusual structure-function of the reduced state of the enzyme. This theme will lead to new ligand scaffolds that stabilize terminal hydride ligands.