Xu Yun-Yu, Jiang Xue-Lian, Chai Jia-Lu, Qiu Shu-Juan, He Juan, Xu Gan, Wei Jia, Yu Qiu-Xiang, Zhang Hong-Ying, Li Yue, Zhang Xiao-Wen, Cao Guo-Liang, Li Yong, Cui Yun-Shu, Xu Cong-Qiao, Li Jun, Chen Xu-Dong
State Key Laboratory of Microbial Technology, Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, Jiangsu 210023, China.
Department of Chemistry and Guangdong Provincial Key Laboratory of Catalytic Chemistry, Southern University of Science and Technology, Shenzhen 518055, China.
Proc Natl Acad Sci U S A. 2025 Jun 17;122(24):e2419655122. doi: 10.1073/pnas.2419655122. Epub 2025 Jun 12.
The FeMo cofactor (FeMoco), the key active site in the Mo-based nitrogenase, is one of the most complicated metalloenzyme molecules. Synthesis of the FeMoco model cluster ([MoFeSC]) is essential to understanding its function in dinitrogen binding, activation, and conversion. However, the complex framework of the FeMoco cluster, which features a unique trigonal prismatic [FeC] moiety comprising a -bridging carbide, has made the synthesis of the cluster a persistent challenge. In this work, two analogous mimics of FeMoco have been synthesized, using a cluster-coupling synthetic strategy facilitated by the fabrication of unsaturated ligand/metal coordination. The incorporation of a -X (X = C or N) to construct the characteristic triangular prismatic [Fe(-X)] moiety, replicating that in FeMoco, has been achieved synthetically. The two mimics have similar key structural parameters to FeMoco in natural nitrogenase, but differ from the FeMoco structure in two major aspects: the -bridging ligands and the metal atoms capping the [FeSC] cores (Mo/Fe in FeMoco vs. Mo/Mo or W/W in the synthetic models). Quantum chemical studies indicate that the electronic ground states of these clusters resemble those observed for FeMoco, with maximized antiferromagnetic coupling among the iron centers. A future systematic study on the physical and chemical properties of a family of mimics with programmed variations of key structural elements can provide a valuable comparison and facilitate a better understanding of the structure and function of FeMoco.
铁钼辅因子（FeMoco）是钼基固氮酶中的关键活性位点，是最复杂的金属酶分子之一。合成FeMoco模型簇（[MoFeSC]）对于理解其在双氮结合、活化和转化中的功能至关重要。然而，FeMoco簇的复杂框架具有独特的包含桥联碳化物的三角棱柱形[FeC]部分，这使得该簇的合成一直是一个挑战。在这项工作中，通过不饱和配体/金属配位的构建促进的簇偶联合成策略，合成了两种类似的FeMoco模拟物。通过合成实现了引入-X（X = C或N）以构建特征性的三角棱柱形[Fe(-X)]部分，这与FeMoco中的部分类似。这两种模拟物在天然固氮酶中具有与FeMoco相似的关键结构参数，但在两个主要方面与FeMoco结构不同：桥联配体和覆盖[FeSC]核心的金属原子（FeMoco中的Mo/Fe与合成模型中的Mo/Mo或W/W）。量子化学研究表明，这些簇的电子基态类似于在FeMoco中观察到的基态，铁中心之间的反铁磁耦合最大化。未来对一系列关键结构元素经过编程变化的模拟物的物理和化学性质进行系统研究，可以提供有价值的比较，并有助于更好地理解FeMoco的结构和功能。
