Bioorganometallic Iron-Sulfide Assemblies Related to Hydrogenases

描述（由申请人提供）：该项目的重点是酶氧化氢气和还原质子以产生氢气的分子机制。氢的加工被许多微生物包括致病微生物所采用，并且涉及极不寻常的辅因子和活性位点。这项工作为铁的新实现的生物功能提供了机械见解，即金属在较低的氧化态下运作，并由CO和氰化物等不寻常的配体支持。这些副本的Fe-唯一的氢化酶的活性位点的机械特性将提供经典酶学表征不可用的见解。初步研究表明，二硫代羰基二铁的氧化脱羰作用提供了与酶的活性位点具有密切结构相似性的物质，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。我们将探索还原Fe-S体系中混合价态的第一个例子。新的二铁模型将被用来产生第一个铁二氢物种，直接相关的催化机制。氧化还原助剂将连接到二铁中心，以探测偶联电子供体和质子受体的动力学和热力学益处。相关的辅助因子的机制作用-无论是氧化还原水库铁-S蛋白和azadithiolate -将被探测。新开发的方法将被应用到相关的机制和制备的挑战有关的NiFe氢化酶：氰化物辅因子的生物合成，赋予新的几何形状，和第二配位球控制质子的可用性。

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.