Nonheme Iron(III)-Superoxo Compounds: Preparation and Characterization of Molecul

描述（由申请人提供）：在临床上重要的抗生素（青霉素、磷霉素和氯霉素）和农药（磷氰菊酯，除草剂Basta和Liberty的一种成分）的生物合成中，关键步骤涉及与非血红素铁酶的双氧反应，包括单核酶异青霉素N合酶和羟乙基膦酸双加氧酶和肌醇加氧酶。这些酶的催化循环被认为涉及一种高活性的铁(III)-超氧中间体作为氧化剂，尽管这种物质已被证明难以分离和表征。合成化合物的制备和表征可以模拟假定的酶中间体的结构（几何和电子），可以为复杂的生物系统提供重要的见解。本文提出了一种新的单核铁-超氧化合物的制备和表征方法。最初的研究将集中于通过与[TpFeIIX] （Tp = hydrotris（pyrazyl）硼酸酯，X = a-酮酸，RC(O)CO2-或烷氧化合物，RO-）的反应捕获假定的Fe(III)-超氧物种。Tp支撑配体和共底物X的空间和电子性质都很容易调整，以延长Fe(III)-超氧物种的寿命。相关中间体将通过各种光谱学（电子吸收、共振拉曼、穆斯堡尔和x射线吸收光谱）和计算（密度泛函理论和时变密度泛函理论）技术进行表征，以生成完整的、经过实验验证的电子结构描述。随后的反应性研究将量化Fe(III)-超氧物质对结合的共底物X和外部有机底物的氧化能力。此外，仅报道了两种合成的二铁-超氧化合物，并且对这两种化合物的电子结构了解甚少。因此，[Fe2(u-OH)2(6-Me3- TPA)2](OTf)2与二氧反应形成的二铁-超氧化合物（Shan， X. and Que， L. Proc. Nat. Acad. science . 2005, 102, 5340）将被彻底表征。先前报道的电子吸收和共振拉曼光谱研究将由穆斯堡尔光谱和x射线吸收光谱以及上述计算技术补充。最后，上述单核和双核模型化合物的实验验证的电子结构描述将用于批判性地评估所提出的Fe(III)-超氧中间体的催化循环。

DESCRIPTION (provided by applicant): Crucial steps in the biosynthesis of clinically important antibiotics (penicillin, fosfomycin, and chlorobiocin) and pesticides (phosphinothricin, a component of the herbicides Basta and Liberty) involve the reaction of dioxygen with nonheme iron enzymes, including the mononuclear enzymes isopenicillin N synthase and hydroxyethylphosphonate dioxygenase and the diiron enzyme myo-inositol oxygenase. The catalytic cycles of these enzymes are thought to involve a highly reactive Fe(III)-superoxo intermediate that acts as an oxidant, though such a species has proven difficult to isolate and characterize. The preparation and characterization of synthetic compounds that mimic the structure (both geometric and electronic) of putative enzymatic intermediates can provide significant insight into complex biological systems. Herein is proposed a new methodology for the preparation and thorough characterization of novel mononuclear iron-superoxo compounds. Initial studies will focus on trapping the putative Fe(III)-superoxo species through the reaction of dioxygen with [TpFeIIX] (Tp = hydrotris(pyrazolyl)borate, X = a-keto acids, RC(O)CO2-, or alkoxides, RO-). The steric and electronic properties of both the Tp supporting ligand and of the cosubstrate X are readily tuned to prolong the lifetime of the Fe(III)-superoxo species. The relevant intermediate will be characterized by a variety of spectroscopic (electronic absorption, resonance Raman, Mossbauer, and X-ray absorption spectroscopies) and computational (density functional theory and time-dependent density functional theory) techniques in order to generate a complete, experimentally-validated electronic structure description. Subsequent reactivity studies will quantify the oxidizing power of the Fe(III)-superoxo species toward the bound cosubstrate X and toward external organic substrates. In addition, only two synthetic diiron-superoxo species have been reported, and the electronic structures of both compounds are poorly understood. Therefore, the diiron-superoxo compound formed upon reaction of [Fe2(u-OH)2(6-Me3- TPA)2](OTf)2 with dioxygen (Shan, X. and Que, L. Proc. Nat. Acad. Sci. 2005, 102, 5340) will be thoroughly characterized. The previously reported electronic absorption and resonance Raman spectroscopic studies will be complemented by Mossbauer, and X-ray absorption spectroscopies, as well as the computational techniques described above. Finally, the experimentally-validated electronic structure descriptions obtained for the mononuclear and dinuclear model compounds described above will be used to critically evaluate the proposed catalytic cycles that invoke Fe(III)-superoxo intermediates. PUBLIC HEALTH RELEVANCE: It is of critical importance to understand the fundamental chemical reactions that are necessary for the production of widely used antibiotics (penicillin, fosfomycin, and chlorobiocin) and pesticides (phosphinothricin, a component of the herbicides Basta and Liberty). The biosynthesis of each of these compounds relies on the interaction of oxygen with iron-containing enzymes in complex biological systems, and the relevant chemical details are poorly understood. In this work, we propose to prepare and thoroughly characterize synthetic complexes that model the structures and reactivities of these enzymes in order to gain insight into the biosynthesis of these clinically- and environmentally-significant compounds.