Designing Polymetallic Clusters to Model the Active site of the FeMo-Cofactor

描述（由申请人提供）：多金属金属酶在自然界中产生许多反应，这些反应包括氧气，氮气和许多其他地球上生命所必需的元素。自然界中二氮还原是由多核金属酶氮酶实现的。底物还原位点由mofe7s7辅因子组成。尽管关于辅助因子的结构信息很好，但关于底物结合和辅助因子在周转过程中的整体化学作用的许多问题仍未得到解答。氮酶的功能模型通常在配体环境中使用单个过渡金属离子，这些配体环境不能忠实地再现自然发生的酶位点。利用新的方法来可靠地合成多金属簇，我们寻求采用定义良好的三金属簇作为构建块来组装辅因子核心模拟。利用在天然酶中发现的化学功能，多胺/硫化物配体系统被提议作为支架来支持三铁核心。更重要的是，定义明确的分子三铁单元将使我们能够系统地检查具有仅铁反应位点的氮酶底物的反应化学，以及合成具有不同间隙原子成分的辅因子的结构模拟物。本提案旨在开发多金属团簇，以在结构和功能上模拟氮酶的femo辅因子。

DESCRIPTION (provided by applicant): Polymetallic metalloenzymes gate many of the reactions in nature which incorporate oxygen, nitrogen and many other elements essential for life on this planet. Dinitrogen reduction is achieved in nature by the polynuclear metalloenzyme nitrogenase. The site for substrate reduction consists of the MoFe7S7-cofactor. Despite good structural information about the cofactor, many questions regarding substrate binding and the overall chemical action of the cofactor during turnover remain largely unanswered. Functional models for nitrogenase often employ single transition metal ions in ligand environments that do not faithfully reproduce the naturally occurring enzyme sites. Utilizing new methodology to reliably synthesize polymetallic clusters, we seek to employ well-defined trimetallic clusters as building blocks to assemble a cofactor core mimic. Using chemical functionalities found within the native enzyme, polyamine/sulfide ligand systems are proposed as scaffolds to support the tri-iron cores. More importantly, the well-defined molecular tri-iron units will allow us to systematically examine the reaction chemistry of nitrogenase substrates with an iron-only reaction site, as well as synthesize structural mimics of the cofactor with differing interstitial atom components. This proposal seeks to develop polymetallic clusters to both structurally and functionally model the FeMo-cofactor of nitrogenase.