BIOLOGICALLY RELATED IRON SULFUR CHEMISTRY

该申请寻求对一项已建立的研究计划的支持， 生物无机化学，旨在从分子水平理解 生物相关的铁硫簇和相关物种。 这些 团簇，特别是Fe 4S 4立方烷型，普遍存在 在所有的生命形式中。 除了其公认的作用外， 蛋白质中基本上是孤立的电子转移中心， 现在已知簇与催化位点共价键合， 自身充当催化位点。 这些是一个更大的 一系列结构和反应性特征，定位于特定的 一个簇的铁子位。 拟议的研究采取新的方向， 具体补贴和其他 铁硫团簇的性质。 这些研究将在以下方面进行： (1)一种新环状化合物的合成及Fe_4S_4簇插入反应 三硫醇及其随后在检查亚单位特异性 （2）确定特定反应的范围; Fe_4S_4团簇的反应特性; 分化，减少集群作为一种手段检查CO抑制 （4）Fe-S酶的亚基特异性反应的表征 乌头酸酶的底物和抑制剂;（5）乌头酸酶的形成和 桥连Fe 4S 4-X组装体（X-Fe 4S 4，Fe，Ni，和 其他金属）可能与固氮酶的P-簇有关， 亚硝酸盐和亚硫酸盐还原酶和一氧化碳的催化单元 （6）立方Fe_3S_4簇合物的形成， Fe-S簇在蛋白质中被发现，通过氧化转化， 亚基分化的Fe 4S 4簇合物或还原异构化 线型Fe_3S_4簇合物的合成;（7）立方烷型杂金属簇合物的合成 通过将生物金属M-Mn、Co、Ni、Cu、Zn插入到MFe 3S 4中， 立方体Fe 3S 4或通过还原掺入，重排， （8）完成六电子还原SO 32- -> S2-和NO2- -> NH3在Fe（II），重点是识别 底物还原的中间状态;（9）制备和 多核环状和双环簇的表征;（10） 高核度Fe-S/Se团簇的制备与表征 如自组装和集群扩大的手段，作为一种途径， 未表征的生物簇，如氢化酶的H簇; (11)利用高核度集群作为一种手段， V-Fe-S和Mo-Fe-S簇合物的制备和表征， 构成V-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.