BIOLOGICALLY RELATED IRON SULFUR CHEMISTRY

此应用程序寻求对以下项目的支持 生物无机化学朝着分子理解的方向发展 生物上相关的铁-硫簇和相关物种。这些 团簇，特别是Fe4S4立方烷类型，是普遍存在的 在所有形式的生命中。除了他们公认的作为 蛋白质中基本孤立的电子转移中心，这些 现在已知团簇以共价键连接到催化中心和 本身就是催化点。这些都是一个更大的 在特定位置本地化的结构和反应性特征的集合 群集的铁子站点。拟议的研究在以下方面采取了新的方向 详细调查表针对具体的子站点和其他 铁-硫团簇的性质。这些研究将会进行： (1)新环状化合物的合成及Fe4S4簇插反应 三硫醇及其在亚位点特异性检测中的应用 性质；(2)划定亚站点特定反应的范围 Fe4S4团簇；(3)CO与亚位反应的表征- 差异化还原团簇作为检测一氧化碳抑制的一种手段 铁-S酶；(4)亚位点特异性反应特性 乌头酸酶的底物和抑制剂；(5)形成和 桥联Fe4S4-X组件(X-Fe4S4、Fe、Ni和 其他金属)可能与固氮酶的P-簇和 亚硝酸盐、亚硫酸盐还原酶和一氧化碳的催化单元 脱氢酶；(6)立方Fe3S4簇的形成，最新 铁-S簇合物存在于蛋白质中，通过氧化转化为 亚位区分的Fe4S4团簇或还原异构化 线型Fe3S4团簇；(7)异金属立方烷型团簇的合成 通过在MFe3S4中插入生物金属M-锰、钴、镍、铜、锌 立方体Fe3S4或通过还原掺入， 线性Fe3S4；(8)完成六电子还原SO32-&GT； Fe(II)上的S2-和NO2--&gt；NH3，着重鉴定 底物还原的中间态；(9)制备和 多核环状和双环状簇合物的表征(10) 高核度Fe-S/Se团簇的制备与表征 自组装和集群扩大等手段，作为通向 未确定的生物簇，如氢酶的H簇； (11)利用高核密度集群作为手段 V-Fe-S和Mo-Fe-S簇合物的制备与表征 组成V-固氮酶和Mo-固氮酶的辅因子。

This application seeks support for an established research program in bioinorganic chemistry directed toward a molecular understanding of biologically relevant iron-sulfur clusters and related species. These clusters, particularly the Fe4S4 cubane-type, are of pervasive occurrence in all forms of life. In addition to their well-recognized role as essentially isolated electron transfer centers in proteins, these clusters are now known to be covalently bonded to catalytic sites and to act as catalytic sites themselves. These are aspects of a larger collection of structural and reactivity features localized at a specific iron subsite of a cluster. The proposed research takes new directions in the form of detailed investigations of subsite-specific and other properties of iron-sulfur clusters. These studies will be undertaken: (1) synthesis and Fe4S4 cluster insertion reactions of a new cyclic trithiol and its subsequent use in examination of subsite-specific properties; (2) delineation of the scope of subsite-specific reactions of Fe4S4 clusters; (3) characterization of the reactions of CO with subsite- differentiated, reduced clusters as one means of examining CO inhibition of Fe-S enzymes; (4) characterization of subsite-specific reactions of the substrate and inhibitors of aconitase; (5) formation and characterization of bridged Fe4S4-X assemblies (X - Fe4S4, Fe, Ni, and other metals) as potentially related to the P-clusters of nitrogenase and the catalytic units of nitrite and sulfite reductases and carbon monoxide dehydrogenases; (6) formation of the cuboidal Fe3S4 cluster, the latest Fe-S cluster to be found in proteins, by oxidation conversion of a subsite-differentiated Fe4S4 cluster or reductive isomerization of a linear Fe3S4 Cluster; (7) synthesis of heterometal cubane-type clusters MFe3S4 by insertion of biological metal M - Mn, Co, Ni, Cu, Zn into cuboidal Fe3S4 or by reductive incorporation in, with rearrangement of, linear Fe3S4; (8) accomplishment of the six-electron reductions SO3 2- -> S2- and NO2- -> NH3 at Fe(II) with emphasis on the identification of intermediate states of substrate reduction; (9) preparation and characterization of polynuclear cyclic and bicyclic clusters; (10) preparation and characterization of high-nuclearity Fe-S/Se clusters by means such as self-assembly and cluster enlargement, as a route to uncharacterized biological clusters such as the Hclusters of hydrogenase; (11) utilization of high-nuclearity clusters as a means to the preparation and characterization of V-Fe-S and Mo-Fe-S clusters that constitute the cofactors of V- and Mo-nitrogenase.