Polynuclear iron complexes as functional mimics of the nitrogenase FeMo-cofactor

描述（由申请人提供）：多核固氮酶辅因子的功能模型氮进入生物圈是所有生物过程的限速步骤，因此，生命本身。二氮的还原发生在多核金属酶，称为固氮酶。含钼酶的反应中心由半胱氨酸连接的MoFe 7S 7辅因子（FeMoco）组成，其中发生二氮固定。尽管良好的结构信息的辅因子，许多问题的底物摄取和整体化学作用的辅因子在营业额仍然存在。具体而言，钼的氧化还原灵活性表明其可能参与底物活化，这已通过功能模型研究进行了审查。然而，位点诱变研究和理论模型表明FeMoco的多核Fe-面参与底物活化。合成的结构类似物已被塑造复制辅因子的组成和阐明结构的细节，模仿辅因子。然而，没有合成模型存在，将允许探测固氮酶底物和多核反应位点之间的相互作用，让人想起那些存在于FeMoco。使用我们实验室开发的合成方法来可靠地合成多核簇，所提出的研究的目标是在功能和结构上模拟FeMoco的活性位点。聚酰胺和聚酰胺/硫化物配体系统允许的隔离和研究定义明确的三核和六核铁配合物。分子三铁单位将允许固氮酶底物的反应化学与铁的唯一反应位点的系统检查。此外，双分子耦合的三铁单位将允许合成和表征的各种结构模拟的辅因子具有不同的间隙原子成分。拟议的研究将允许测试几个假设固氮酶底物与FeMoco中普遍存在的多核反应位点的相互作用。

DESCRIPTION (provided by applicant): Functional models of the polynuclear nitrogen-fixing enzyme cofactors Nitrogen entry into the biosphere is the rate-limiting step for all biological processes, and therefore, life itself. Dinitrogen reduction occurs at polynuclear metalloenzymes called nitrogenase. The reaction center of the Molybdenum-containing enzyme consists of a cysteine ligated MoFe7S7 cofactor (FeMoco) where dinitrogen fixation takes place. Despite good structural information about the cofactor, many questions regarding substrate uptake and the overall chemical action of the cofactor during turnover remain. Specifically, the redox flexibility of Mo point to its likely involvement in substrate activation, which has been vetted by functional model studies. However, site-mutagenesis studies and theoretical models indicate a polynuclear Fe-face of FeMoco to participate in substrate activation. Synthetic structural analogues have been fashioned to reproduce the cofactor composition and elucidate structural details that mimic the cofactor. However, no synthetic models exist that would permit probing of the interaction between nitrogenase substrates and a polynuclear reaction site reminiscent of those present in FeMoco. Using synthetic methodology developed in our laboratories to reliably synthesize polynuclear clusters, the goal of the proposed research is to both functionally and structurally model the active site of FeMoco. Polyamide and polyamide/sulfide ligand systems permit the isolation and study of well-defined tri- and hexanuclear iron complexes. The molecular tri-iron units will allow systematic examination of the reaction chemistry of nitrogenase substrates with an iron-only reaction site. Furthermore, bimolecular coupling of tri-iron units will permit the synthesis and characterization of various structural mimics of the cofactor featuring different interstitial atom components. The proposed research will permit the testing of several hypotheses concerning interaction of nitrogenase substrates with polynuclear reaction sites prevalent in FeMoco.