Sterically Hindered Carboxylates for Modeling Nonheme Iron Proteins

生物无机和金属有机化学项目的这一奖项支持明尼苏达大学的William B.Tolman和Lawrence Que教授对羧酸桥联双铁酶的合成模型进行详细研究，例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。在这项研究中，空间大体积的羧酸盐配体将被用来控制复杂的成核性和配位数(S)，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。羧酸盐和共结合的N-给体配体的空间性质的变化将被用来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。这些络合物将作为活性中间体的前体，被捕获在与氧、超氧化物和过氧化物的反应中。铁-氧中间体形成反应和相互转化的瞬时物种和反应机理将通过动力学研究进行评估。这项工作将涉及与E.Munck(Mossbauer，Carnegie-Mellon U)和E.Rybak-Akimova(低温停流动力学，TuftU)的合作。这项研究将阐明非血红素铁酶的功能，这些酶在具有生物学和环境意义的过程中发挥核心作用。这些过程与工业中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对广义催化产生影响。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的环境中接受培训。

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.