Bioorganometallic Iron-Sulfide Assemblies Related to Hydrogenases

项目描述（由申请人提供）：该项目重点研究氢化酶的作用机制，其中有两种酶，[NiFe]-和[FeFe]-氢化酶，反映活性位点的金属。这些酶支持人类肠道中许多病原体的H2依赖性代谢，作用于两种底物质子（H+）和H2。几个相关的酶家族是已知的。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。特别关注的是h2衍生底物的位置和行为，这些底物通常是蛋白质光谱不可见的，也是蛋白质晶体学无法检测到的。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，在[FeFe]的情况下，氨基二硫酸盐。这项工作采用了有机金属化学的工具来产生活性位点的模型（复制品）。分子水平上对氢配体行为的洞察将通过核磁共振波谱和x射线晶体学进行检查，并关注立体化学，氧化还原电位，酸碱行为和动力学性质。第一个主题探讨了稳定镍ii的方法，N-C状态的特点，使用有机金属配体，模拟硫代盐配体的供体性质。第二个主题考察了与铁结合的氰化物辅因子的作用，重点是开发工具来改变这些基团的行为。这一目的建立在初步证据，硼试剂使氢在氰化铁仿生活化。第三个主题，主要关注[FeFe]酶，阐明了导致双向性的因素，模型产生和氧化H2的能力。最后一个主题，也强调了[FeFe]-氢化酶，检验了试图解释酶还原状态的不寻常结构-功能的假设。这一主题将导致稳定末端氢化物配体的新配体支架。

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.