Biologically Related Iron-Sulfur Chemistry

本申请寻求对生物无机化学中已建立的研究项目的持续支持，该项目旨在对含有铁、硫和其他金属的生物相关簇进行详细的分子理解，这些金属在生命的各个层面都有发现。除了它们作为电子载体的经典作用外，这些簇现在还被认为是氧化还原和非氧化还原转化的催化中心，以及某些细胞过程的传感器和调节剂。在对三种最普遍的团簇类型（[2Fe-2S], [3Fe-4S], [4Fe-4S]）有了大致的了解之后，人们的注意力也集中在了含有异质金属如钼，钒和镍的更复杂的团簇上。在酶氮酶和一氧化碳脱氢酶/乙酰辅酶A合酶中，电子转移和催化位点是由两个或多个共价键连接的离散片段的桥接组装。本研究旨在利用合成模拟方法阐明簇和桥接组合体的形成途径、几何结构和反应性，其目标是高分辨率检测活性位点的结构和功能表征。在提出的研究问题中，包括在氮酶中发现的全铁[4Fe-4S]氧化态，裂解s -腺苷蛋氨酸的反应性类似物，转化硫的来源

This application seeks continued support for an established research program in bioinorganic chemistry directed at a detailed molecular understanding of biologically relevant clusters containing iron, sulfur, and other metals, various types of which are found at all levels of life. In addition to their classical role as lectron carriers, these clusters are now known to function as catalytic centers for redox and non-redox transformations, and as sensors and regulators for certain cellular processes. With a general understanding of the three most pervasive cluster types ([2Fe-2S], [3Fe-4S], [4Fe-4S]) in hand, attention is also focused on more complex clusters which contain heterometals such as molybenum, vanadium, and nickel. In the enzymes nitrogenase and carbon monoxide dehyrogenase/acetylcoenzyme A synthase, the electron transfer and catalytic sites are bridged assemblies in which discrete fragments are linked by two or more covalent bonds. This research seeks elucidation of the pathways of formation, geometrical structures, and reactivity properties of clusters and bridged assemblies using the synthetic analogue approach, whose objectives are structural and functional representations of active sites that can be examined at high resolution. Among the problems proposed for investigation are the all-ferrous [4Fe-4S] oxidation state found in nitrogenase, reactivity analogues for the cleavage of S-adenosylmethionine, the source of sulfur for the conversion of dethiobiotin to biotin, synthesis of analogues of the electron-transfer and catalytic cofactor clusters of nitrogenase and the catalytic clusters of carbon monoxide dehydrogenase. Throughout there is much emphasis on original synthetic chemistry aimed toward the attainment of weak-field clusters that are meaningful analogues, or are the same as, enzymes sites. A significant portion of the proposed research is intended to contribute to the developing area of metallocenter synthesis and biosynthesis by showing what synthetic routes are feasible for cluster formation.