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。二氮还原发生在称为氮酶的多核金属酶中。含钼酶的反应中心由半胱氨酸连接的MoFe7S7辅因子（FeMoco）组成，在此进行二氮固定。尽管关于辅助因子的结构信息很好，但关于底物摄取和辅助因子在周转过程中的整体化学作用的许多问题仍然存在。具体来说，Mo的氧化还原柔韧性表明它可能参与底物活化，这已经被功能模型研究证实。然而，位点诱变研究和理论模型表明，FeMoco的多核fe面参与底物激活。合成的结构类似物被用来复制辅因子的组成并阐明模仿辅因子的结构细节。然而，目前还没有合成模型可以探测到氮酶底物和多核反应位点之间的相互作用，这些反应位点与FeMoco中的反应位点类似。利用我们实验室开发的合成方法来可靠地合成多核簇，提出的研究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分离和研究明确的三核和六核铁配合物。分子三铁单元将允许系统地检查反应化学的氮酶底物与铁的反应位点。此外，三铁单元的双分子偶联将允许合成和表征具有不同间隙原子成分的辅因子的各种结构模拟物。拟议的研究将允许测试几种关于氮酶底物与FeMoco中普遍存在的多核反应位点相互作用的假设。

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.