Bioorganometallic Iron-Sulfide Assemblies Related to Hydrogenases

描述(由申请者提供)：该项目重点研究酶氧化氢气和还原质子制造氢气的分子机制。氢气的加工被许多微生物包括致病微生物所利用，并且涉及到非常不寻常的辅因子和活性部位。这项工作提供了对铁新实现的生物功能的机械见解，即金属在较低的氧化态下工作，并由不寻常的配体支持，如一氧化碳和氰化物。对这些只含铁的氢酶活性部位的复制体的机械表征将提供经典的酶学表征所不能提供的见解。初步研究表明，二硫代甲酸铁的氧化脱羧反应提供了与该酶的活性部位具有密切结构相似性的物种，例如以前未观察到的桥联CO配体。该项目将建立在这些初步成功的基础上，目标是按照机械酶学家的预测，产生与氢化底物结合的物种。我们将探索约化Fe-S系统中混合价的第一个例子。新的二亚铁模型将被用来产生第一个与催化机理直接相关的铁二氢物种。氧化还原助剂将被连接到双铁中心，以探索偶联电子供体和质子受体的动力学和热力学益处。相关的辅因子-氧化还原储存库的铁-S蛋白和氮二硫代谢物-的机制作用将被探索。新开发的方法将应用于与NiFe氢酶相关的机械和制备挑战：氰化物辅因子的生物合成，赋予新几何构型的金属茂硫醚的生物合成，以及质子有效性的第二配位球控制。

DESCRIPTION (provided by applicant): The project focuses on molecular mechanisms by which enzymes oxdize hydrogen gas and reduce protons to make hydrogen. The processing of hydrogen is employed by many micro-organisms including pathogenic ones and involves extremely unusual cofactors and active sites. The work provides mechanistic insights into the newly realized biological function of iron, i.e. where the metal operates at lower oxidation states and is supported by unusual ligands such as CO and cyanide. Mechanistic characterization of these replicas of the active site of the Fe-only hydrogenase will provide insights unavailable by classical enzymological characterization. Preliminary studies show that oxidative decarbonylation of diiron dithiolato carbonyls affords species that bear a close structural resemblance to the enzyme's active sites, such as the previously unobserved bridging CO ligand. The project will build on these initial successes with the goal of generating species with hydrogenic substrates bound as predicted by mechanistic enzymologists. We will probe for the first examples of mixed valency in reduced Fe-S systems. The new diferrous models will be employed to generate the first iron dihydrogen species, directly relevant to the catalytic mechanism. Redox auxiliaries will be attached to the diiron center to probe the kinetic and thermodynamic benefits of coupling the electron donor and the proton receptor. The mechanistic role of the associated cofactors - both the redox reservoir Fe-S protein and azadithiolate - will be probed. The newly developed methodologies will be applied to related mechanistic and preparative challenges related to the NiFe hydrogenases: the biosynthesis of the cyanide cofactor, metallocenethiolates to confer novel geometries, and second coordination sphere control of proton availability.