Sterically Hindered Carboxylates for Modeling Nonheme Iron Proteins

这个生物无机和有机金属化学项目的奖项支持明尼苏达大学的William B. Tolman教授和Lawrence Que教授对羧酸酯桥接二铁酶的合成模型的详细研究，如核糖核苷酸还原酶、甲烷单加氧酶、甲苯单加氧酶和硬脂酰ACP去饱和酶。在本研究中，立体体积的羧酸配体将用于控制复杂的核和配位数，以及为稳定反应中间体和影响氧化还原电位提供疏水屏蔽。羧酸酯和共结合的n给体的空间性质的变化将用于控制配合物的结构属性，并有目的地访问单铁和双铁配合物。这些配合物将作为反应中间体的前体，在与氧、超氧化物和过氧化物的反应中被捕获。铁氧中间体形成反应和相互转化的瞬态物质和反应机制将通过动力学研究进行评估。这项工作将涉及与E. Munck（穆斯堡尔大学，卡内基-梅隆大学）和E. Rybak-Akimova（塔夫茨大学，低温停流动力学）的合作。该研究将阐明非血红素铁酶的功能，在生物和环境意义的过程中发挥核心作用。这些过程与工业上的催化反应密切相关，因此在研究过程中获得的基础知识将在广义上影响催化。研究生将在包括明尼苏达大学金属生物催化中心在内的高度多学科环境中接受培训。

This award in the Bioinorganic and Organometallic Chemistry Program supports Professors William B. Tolman and Lawrence Que at the University of Minnesota for detailed studies on synthetic models of carboxylate bridged di-iron enzymes, such as ribonucleotide reductase, methane monooxygenase, toluene monooxygenase, and stearoyl ACP desaturase. In this research, sterically bulky carboxylate ligands will be used to control complex nuclearity and coordination number(s), as well as to provide hydrophobic shielding for stabilizing reactive intermediates and influencing redox potentials. Variation of the steric properties of the carboxylates and co-incorporated N-donor ligands will be used to control the structural attributes of the complexes and purposefully access both mono- and diiron complexes. These complexes will serve as precursors of reactive intermediates to be trapped in the reactions with oxygen, superoxide, and peroxides. Transient species and reaction mechanisms for iron-oxygen intermediate formation reactions and interconversions will be assessed by kinetics studies. This work will involve collaborations with E. Munck (Mossbauer, Carnegie-Mellon U) and E. Rybak-Akimova (cryogenic stopped-flow kinetics, Tufts U). The research will elucidate the functioning of nonheme iron enzymes that play central roles in processes of biological and environmental significance. These processes are closely related to catalytic reactions in industry, so that the fundamental knowledge acquired during the course of the research will impact catalysis in a broad sense. Graduate students will be trained in a highly multidisciplinary environment involving the Center for Metals in Biocatalysis at the University of Minnesota.