Bioorganometallic Iron-Sulfide Assemblies Related to Hydrogenases

该项目的重点是酶氧化氢气和还原质子的分子机制。 来制造氢气。氢的处理被许多微生物使用，包括致病菌 一种，涉及极不寻常的辅因子和活性部位。这项工作提供了对 新实现的铁的生物功能，即金属在较低的氧化态下运行，并 由CO和氰化物等不寻常的配体支撑。这些复制品的机械特征 只有铁的氢酶的活性部位将提供经典酶学无法提供的见解 人物刻画。 初步研究表明，二硫代二硫代烷基铁的氧化脱羰基提供了 与酶的活性部位有密切的结构相似之处，例如以前没有观察到的桥接 共同配基。该项目将建立在这些初步成功的基础上，目标是通过 生氢底物如机械论酶学家所预测的那样结合。我们将探索第一个 约化Fe-S体系中混合价的例子。新的有色金属模型将被用于 生成第一种铁二氢物种，与催化机理直接相关。氧化还原助剂将 连接到双铁中心以探测耦合电子的动力学和热力学益处 供体和质子受体。相关辅因子的机械作用--既包括氧化还原储存库 铁-S蛋白和硫代氮杂多酸-将被探索。新开发的方法将应用于 与NiFe氢酶相关的机制和制备挑战： 氰化物辅因子，金属硫代化合物赋予新的几何构型，以及第二配位球控制 质子可获得性。

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 successeswith 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 availabilit.