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包括病原微生物 其中包括极不寻常的辅因子和活性位点。这项工作提供了机械的见解， 铁的新实现的生物功能，即金属在较低氧化态下起作用， 由不寻常的配体如CO和氰化物支撑。这些复制品的机械特性 只有铁氢化酶的活性位点将提供经典酶学无法提供的见解， 特征化 初步研究表明，二硫羟羰基二铁的氧化脱羰提供了 与酶的活性位点在结构上非常相似，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， 如机械酶学家所预测的那样结合类氢底物。我们将探索 还原Fe-S系统中混合价态的实例。新的有色金属模型将用于 产生与催化机理直接相关的第一种二氢铁物质。氧化还原助剂将 被连接到二铁中心，以探测耦合电子的动力学和热力学益处 供体和质子受体。相关辅因子的机制作用-氧化还原库 Fe-S蛋白和氮杂二硫醇盐-将被探测。新开发的方法将应用于 与NiFe氢化酶相关的相关机制和制备挑战： 氰化物辅因子、赋予新几何形状的噻吩硫醇盐和第二配位球控制 质子的可用性。

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.