Exploring the effects of multi-iron site cooperativity and second sphere ligand interactions on NN bond cleavage in high-spin iron complexes

 说明(申请人提供)：固氮酶是一种酶，它能够裂解看似惰性的NN三键，形成生物可利用的氨。该酶利用结构上史无前例的铁-S簇，铁-钼辅助因子“FeMoCO”，将氮还原为氨。对基础Fe-N化学以及Fe配位的变化以及周围环境如何影响络合物还原N_2的能力的研究将有助于深入了解固氮酶的机制。这些特征的效果将通过合成分解和简化FeMoco的络合物来测试，从而允许每个特征对Fe-N化学的研究。FeMoco包含生物中唯一的碳化物例子，然而，碳化物如何影响Fe中心及其还原氮气的能力仍然是推测的。在合成的络合物中，Fe-S和Fe-碳化物团簇与N_2的相互作用尚不清楚，具有这些配体的Fe-N_2络合物的发展将为固氮酶的作用机理提供化学基础。我们的指导性假设是，氮气通过Fe-C键或Fe-S键的断裂与簇结合，产生一个氮络合物，在酶的周转过程中可以与活性中心附近的残基相互作用。在拟议的研究中，我们计划合成具有新功能的Fe-N_2络合物：(1)第二球状质子基，我们假设与以前报道的需要强酸的体系相比，它将允许使用较温和的试剂将氮还原为氨；(2)引入富电子的阴离子硫配体应该会增加Fe的供体能力，使结合的N_2更容易还原；以及(3)形成也与N_2结合的铁碳化物络合物，以通过合成类似物探索富电子碳化物在固氮酶中的作用。每组新的配合物都将通过反应性、动力学和X射线结晶学研究，以了解每一组化合物如何影响铁和氮之间的相互作用。通过EPR、Endor和EXAFS等光谱技术研究这些配合物，将为固氮酶数据的化学和结构解释提供支持。

 DESCRIPTION (provided by applicant): Nitrogenase is an enzyme that is able to cleave the seemingly inert NN triple bond to form biologically available ammonia. The enzyme employs a structurally unprecedented Fe-S cluster, the iron-molybdenum cofactor, "FeMoco," to reduce N2 to NH3. Examination of fundamental Fe-N2 chemistry and how changes in coordination at Fe as well as the surrounding environment influence the ability of complexes to reduce N2 in will offer insight to the mechanism of nitrogenase. The effects of these features will be tested by synthesis of complexes that divide and simplify the FeMoco allowing for the study each feature has on Fe-N2 chemistry. The FeMoco contains the only example of a carbide in biology, however, how the carbide effects the Fe centers and their ability to reduce N2 remains speculative. Interactions of Fe-S and Fe-carbide clusters with N2 is unknown in synthetic complexes, and development of Fe-N2 complexes that do possess these ligands will provide a chemical basis for the proposed mechanisms of nitrogenase. Our guiding hypothesis is that N2 binds to the cluster through cleavage of either a Fe-C bond or Fe-S bond leading to a N2 complex that can interact with residues nearby the active site during enzyme turnover. In the proposed research, we plan to synthesize Fe-N2 complexes with novel functionalities: (1) second-sphere protic groups, which we hypothesize will allow for use of milder reagents for N2 reduction to ammonia compared with the systems reported previously that required strong acids, (2) introduction of electron-rich, anionic sulfur ligands should increase the donating abiliy of Fe making the bound N2 easier to reduce, and (3) formation of an Fe-carbide complex that also binds N2 to explore the role of the electron-rich carbide in nitrogenase through a synthetic analogue. Each new set of complexes will be examined through reactivity, kinetic, and X-ray crystallographic studies to understand how each impacts the interaction between Fe and dinitrogen. Study of these complexes through spectroscopic techniques such as EPR, ENDOR, and EXAFS will offer support for the chemical and structural interpretation of the data from nitrogenase.