Bioorganometallic Iron-Sulfide Assemblies Related to Hydrogenases

与氢化酶相关的生物有机金属硫化铁组装体

• 批准号: 7570691
• 负责人: Thomas Rauchfuss
• 金额: $ 23.65万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7570691
• 关键词: Acids; Active Sites; Anabolism; Binding; Biological; Biological Process; Catalysis; Complex; Coupling; Cyanides; Electrons; Enzymes; Family; Gases; Goals; Hydrogen; Hydrogenase; Iron; Kinetics; Knowledge; Ligands; Metals; Methodology; Modeling; Molecular; Molecular Weight; Nature; Organism; Oxidation-Reduction; Pathway interactions; Phosphines; Process; Property; Proteins; Protons; Research Personnel; Role; Site; Sulfides; System; Testing; Thermodynamics; Ursidae Family; Work; analog; asparagusic acid; base; cofactor; electron donor; ferrocene; insight; iron cyanide; iron hydrogenase; nickel-iron hydrogenase; novel; oxidation; protonation; receptor; theories

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.

该项目侧重于酶氧化氢气和减少质子的分子机制