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

描述（由申请人提供）：多金属金属酶门在自然界中的许多反应，其中包括氧，氮和许多其他元素的生命在这个星球上必不可少的。在自然界中，二氮的还原是通过多核金属酶固氮酶实现的。底物还原的位点由MoFe 7S 7-辅因子组成。尽管良好的结构信息的辅因子，许多问题，底物结合和整体化学作用的辅因子在营业额仍然在很大程度上没有答案。固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复制天然存在的酶位点。利用可靠合成多金属簇的新方法，我们寻求使用定义明确的三金属簇作为构建模块来组装辅因子核心模拟物。使用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位将使我们能够系统地研究固氮酶底物的反应化学与铁唯一的反应位点，以及合成结构模拟的辅因子与不同的间隙原子成分。该建议旨在开发多金属簇，以在结构和功能上模拟固氮酶的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.