Functional LnFe-NxHy Models of Biological N2 Fixation

功能LnFe-NxHy模型生物固氮酶(N2ase)是一种金属酶，介导生物固氮，对维持生命至关重要。因此，对固氮酶的研究引起了生物和化学界的密切关注。尽管如此，固氮酶在环境条件下促进生物还原氮素的机制仍然是一个令人着迷和尚未解决的问题。我们研究的广泛目标是评估单一铁位能够在合成模型系统中调解催化氮气还原的机制，进而在生物学中。拟议的计划是设计和研究仿生Fe-NxHy模型络合物来实现这一目标。我们的实验方法强调功能上的，而不是结构上的，铁钼辅因子(FeMoco)的忠实模型。将开发低分子量Fe-NxHy络合物，以探索局部4-和5-坐标几何构型中的铁位置，这些几何构型可能容纳氮素和其他NxHy官能团。我们假设这些几何构型与FeMoco的Fe-NxHy中间体有关。通过类比生物催化还原氧气的模式，将评估两种限制机制。第一种是交替的机制，其中连续的质子化以交替的方式在Fe-N？N亚基的远端和近端的N原子上发生(例如，Fe-N=NH？Fe-NH=NH？Fe-NH-NH2？Fe-NH2-NH2？Fe-NH_2 NH_3)。第二种是远端机制，其中远端N原子的完全质子化先于近端N原子的质子化(例如，Fe-N23e-3H？Fe？N NH_3)。我们将使用合成的模型络合物来了解Fe-NxHy物种的成核性、局部几何形状和电子结构如何控制它们的相对稳定性和反应模式。其目的是将这一知识应用于设计能够促进催化N2ase活性的模型系统。无论FeMoco还原氮气的精确机制如何，其最终解决方案将需要将辅助因子的光谱数据与定义明确的模型络合物获得的相关数据进行比较。我们将与专门从事FeMoco光谱研究的研究人员合作，进行这样的比较。总之，所提出的功能性Fe-NxHy模型化学将继续与目前旨在揭示生物固氮的化学机制的生化、光谱和理论模型研究一起发挥关键作用。

DESCRIPTION (provided by applicant): Functional LnFe-NxHy Models of Biological N2 Fixation Nitrogenase (N2ase) is a metalloenzyme that mediates biological nitrogen fixation and is essential to sustain life. As such, the study of nitrogenase attracts intense scrutiny among the biology and chemistry communities. Nonetheless, the mechanism by which nitrogenase enzymes promote the biological reduction of nitrogen under ambient conditions remains a fascinating and unsolved problem. The broad goal of our research is to evaluate the mechanisms by which a single iron site is able to mediate catalytic N2 reduction in synthetic model systems and, by extension, in biology. The proposed program is to design and study biomimetic Fe-NxHy model complexes to address this goal. Our experimental approach stresses functionally, rather than structurally, faithful models of the iron-molybdenum cofactor (FeMoco). Low molecular weight Fe-NxHy complexes will be developed to explore iron sites in local 4- and 5-coordinate geometries that may accommodate dinitrogen and other NxHy functionalites. We posit these geometries as relevant to Fe-NxHy intermediates of the FeMoco. By analogy to the modes of biocatalytic O2 reduction, two limiting mechanisms will be evaluated. The first is an alternating mechanism, where successive protonations occur at the distal and proximal N-atoms of the Fe-N?N subunit in an alternating fashion (e.g., Fe-N=NH ? Fe-NH=NH ? Fe-NH-NH2 ? Fe-NH2-NH2 ? Fe-NH2 + NH3). The second is a distal mechanism, where complete protonation at the distal N-atom precedes protonation at the proximal N-atom (e.g., Fe-N2 + 3 e- + 3 H+? Fe?N + NH3). We will use synthetic model complexes to understand how the nuclearity, local geometry, and electronic structure of Fe- NxHy species control their relative stabilities and reactivity patterns. The intent is to apply this knowledge to design model systems that can facilitate catalytic N2ase activity. Regardless of the precise mechanism for nitrogen reduction at the FeMoco, its ultimate solution will require comparison of spectroscopic data from the cofactor to related data obtained for well-defined model complexes. We will collaborate with researchers that specialize in spectroscopic studies of the FeMoco to make such comparisons. In sum, the functional Fe-NxHy model chemistry proposed will continue to play a critical role alongside current biochemical, spectroscopic, and theoretical model studies aimed at unraveling the chemical mechanism of biological nitrogen fixation.