Bioorganometallic Iron-Sulfide Assemblies Related to Hydrogenases

描述(由申请人提供)：该项目重点研究氢酶的作用机制，其中有两种，[NiFe]-氢酶和[FeFe]-氢酶，反映活性部位的金属。这些酶支持人类肠道中许多病原体依赖于H2的新陈代谢，作用于两种底物质子(H)和H2。已知几个相关的酶家族。这一结果进一步与基础催化剂技术有关。本工作旨在阐明[NiFe]-氢酶的Ni-C、Ni-SI、Ni-R和Ni-L态以及[FeFe]-氢酶的HRED态的结构和活性。特别关注的是氢衍生底物的位置和行为，这些底物通常是蛋白质光谱看不到的，也是蛋白质结晶学无法检测到的。这些酶的活性部位非常不寻常，有几个独特的辅助因子，如一氧化碳、氰化物，在[FeFe]的情况下，还有一个氨基二硫酸盐。这项工作使用了有机金属化学的工具来制作活性中心的模型(复制品)。核磁共振光谱和X射线结晶学将在分子水平上对类氢配体的行为进行检查，重点关注立体化学、氧化还原电位、酸碱行为和动力学性质。第一个主题考察了稳定镍III的方法，该方法具有N-C状态的特征，使用模仿硫代配体的给体性质的有机金属配体。第二个主题研究了与铁结合的氰化物辅助因子的作用，并注意开发工具来改变这些群体的行为。这一目标建立在初步证据的基础上，即硼试剂能够仿生激活氰化铁中的氢。第三个主题主要集中在[FeFe]酶上，阐明了导致双向性的因素，即模型产生和氧化氢气的能力。最后一个主题也强调了[FeFe]-氢酶，它检验了试图解释酶还原状态的不寻常结构-功能的假说。这一主题将导致稳定末端氢化物配体的新的配体支架。

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.