Reactivity-Activation of O(2) or NO in Copper and Heme-Cu Coordination Complexes

项目摘要 拟议的调查源于两个正在进行的R01通用汽车研究项目。研究目标 包括合成模型的设计、合成和研究，这将有助于阐明 与铜和血红素/M有关的结构、M-连接、光谱和反应性的基本方面 (M=铜、铁)分子氧(O2(G))和一氧化氮(NO(G))的处理。令人担忧的铜蛋白 包括裂解多糖单加氧酶(LPMOS)、颗粒甲烷单加氧酶 (PMMOS)，包括多巴胺β-单加氧酶(DBM)和肽甘氨酸在内的酶家族 单加氧酶(PHM)和偶联的双核铜蛋白NSPF。最新的生化研究 对其活跃站点的性质和涉及的行动机制(S)提出了质疑 O2(G)活化和C-H羟化。LPMO可能是过氧酶(双氧水共底物)，新的pMMO 研究表明，这是一个单一的铜活性中心，现在质疑是否DBM和PHM激活 以铜为中心的O2与以Cu2为中心的过程。与这些问题相关的问题，显然需要综合 并表征了迄今难以捉摸的铜(II)-氧基(CuII-O·)物种；它具有所需的氧化能力 对于困难的LPMO或PMMO基板。我们还计划阐明对O-O至关重要的基本原理 发生在所有单加氧酶(&加氧酶)中的还原裂解过程。此外，我们还将生成和 新型高价双核铜(II)-O-铜(III)的结构、物理性质和反应活性的表征 或相关的复合体。否则，建议的研究将集中在目前存在的血红素-铜活性中心。 在细胞色素c氧化酶中，O2-结合并被还原裂解，得到两个摩尔当量的水。这个 对合成模型的研究有助于阐明细节并有助于理解结构、O2结合、 质子或氢键促进O-O裂解，以及活性中心苯酚(在His-Tyr中)的作用 辅因子)作为质子-电子供体。建议进行调查，以进一步研究这些机制 在血红素-过氧铜结构中的O-O裂解，其中卟啉，铁轴向配体和 尤其是铜离子的配位体，是系统变化的。计划了各种方法， 包括对具有三个N-给体和一个附加苯酚的铜的新型络合物的研究。否(G) 还将开展铜和血红素-M的合成模型化学子项目。用铜 络合物，重点将集中在NO(G)还原偶联，并研究与以下有关的机理 NO(G)与金属离子(S)的结合，形成N-N键，生成可能的次亚硝酸盐N2O22- 中间体，以及质子和/或氢键对N-O裂解和N2O形成的贡献。 血红素/铁(或铜)介导的NO(G)还原偶联在NO还原酶和化学中起关键作用 将对这一过程的合成模型进行研究。金属-过氧亚硝酸盐(Pn，来自金属离子O2(G)) NO(G))的反应性，特别是对二氧化碳的反应性，也将与相关的生物活性进行研究。

Project Summary Proposed investigations derive from two on-going R01 GM research programs. The study objectives include the design, synthesis & investigation of synthetic models which will aid the elucidation of fundamental aspects of structure, M-ligation, spectroscopy and reactivity relevant to copper and heme/M (M = Cu, Fe) processing of molecular oxygen (O2(g)) and nitric oxide (NO(g)). Copper proteins of concern include lytic polysaccharide monooxygenases (LPMOs), particulate methane monooxygenases (pMMOs), the enzyme family which includes dopamine beta-monooxygenase (DBM) and peptidylglycine monooxygenase (PHM), and a coupled binuclear copper protein, NspF. Recent biochemical research has raised questions concerning the nature of their active sites and the mechanism(s) of action involving O2(g) activation and C-H hydroxylation. LPMOs may be peroxygenases (H2O2 co-substrate), new pMMO studies suggest a mono-Cu active site, and it is now questioned as to whether DBM and PHM activate O2 with a Cu versus a Cu2 center process. Relevant to these issues, there are clear needs to synthesize and characterize the thus-far elusive copper(II)-oxyl (CuII-O·) species; it has the oxidizing ability needed for the difficult LPMO or pMMO substrates. We also plan to elucidate fundamentals critical to the O-O reductive cleavage process occurring in all monooxygenases (& oxidases). Also, we will generate and characterize the structures, physical properties and reactivity of new high-valent binuclear Cu(II)-O-Cu(III) or related complexes. Otherwise, proposed research will focus on the heme-copper active site present in cytochrome c oxidases, where O2-binds and is reductively cleaved to give two mole-equiv water. The study of synthetic models can help elucidate details and aid an understanding of structure, O2-binding, proton or H-bonding facilitated O-O cleavage, and the role of the active-site phenol (in the His-Tyr cofactor) as a proton-electron donor. Investigations are proposed to further investigate the mechanisms of O-O cleavage in heme-peroxo-copper constructs, where the porphyrinate, the Fe axial ligand and especially the ligand for copper ion, are systematically varied. A variety of approaches are planned, including study of new chelates for copper which possess three N-donors and an appended phenol. NO(g) synthetic model chemistry sub-projects with copper and heme-M will also be carried out. With copper complexes, the focus will be on NO(g) reductive coupling, and investigation of mechanisms pertaining to the NO(g) binding to metal ion(s), formation of the N–N bond giving putative hyponitrite N2O22– intermediates, and proton and/or H-bonding contributions to N–O cleavage and formation of N2O. Heme/Fe (or Cu) mediated NO(g) reductive coupling is critical in NO-Reductases and chemistry and synthetic models for this process will be investigated. Metal-peroxynitrite (PN, from metal ion + O2(g) + NO(g)) reactivity, especially toward CO2, will also be studied in relation to the relevant biological activity.