Bioorganometallic Iron-Sulfide Assemblies Related to Hydrogenases

项目描述（申请人提供）：该项目主要研究酶氧化氢气和还原质子生成氢气的分子机制。氢的处理被许多微生物所利用，包括病原微生物，并且涉及非常不寻常的辅助因子和活性位点。这项工作为铁新实现的生物功能提供了机制见解，即金属在低氧化态下运作，并由CO和氰化物等不寻常的配体支持。对这些纯铁氢化酶活性位点复制品的机制表征将提供经典酶学表征所无法获得的见解。初步研究表明，二硫代二铁羰基的氧化脱碳作用提供了与酶活性位点结构相似的物质，例如以前未观察到的桥接CO配体。该项目将建立在这些初步成功的基础上，目标是产生与机械酶学家预测的氢底物结合的物种。我们将探索在还原Fe-S系统中混合价的第一个例子。新的二铁模型将用于生成与催化机制直接相关的第一个二氢铁物种。氧化还原助剂将附着在双铁中心，以探测耦合电子供体和质子受体的动力学和热力学效益。相关的辅助因子-氧化还原储层Fe-S蛋白和氮二硫酸盐-的机制作用将被探讨。新开发的方法将应用于与NiFe氢化酶相关的机制和制备挑战：氰化物辅助因子的生物合成，赋予新几何形状的茂硫代金属，以及质子可用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.