LIGAND BRIDGED BINUCLEAR METAL COMPLEXES AND PROTEINS

这项研究的主要目的是阐明化学和 配体桥联双金属和多金属的物理性质 以蛋白质和相关模型化合物为中心。注意力将会 关注二铁氧合蛋白杂氰菊酯(HR)，甲烷单氧- 酶(MMO)、核糖核酸还原酶(RR)和紫酸 磷酸酶(PAP)和铁储存蛋白铁蛋白(Ft)。 其中的具体目标是建立双核铁分子 对烃类具有可逆的结合和催化作用 02的氧化，以结构和光谱表征 并在MMO中模拟双铁中心，并构建新的 聚铁氧络合物作为铁蛋白核心模型。一个重要的目标 就是发现结构和结构之间的基本关系 功能。配位化学有哪些特点？ 几何相似的双核铁中心促进可逆02 HR结合，RR中核糖核酸还原为脱氧核糖核酸， MMO中的甲烷氧化和PAP中的磷酸酯水解？ 是什么反应控制着导致铁氧齐聚的步骤 到福特堡的聚铁芯组装？这些问题的答案是 这些问题有许多与健康相关的含义。RR催化了 DNA生物合成的第一步，以及抑制 其功能具有抗肿瘤和化疗的潜力 抗病毒药物。新型氧转运分子的制备 可以帮助开发人造血液替代品。 了解铁的水解聚合反应是怎样的 受控可能导致更好地管理其生物 毒物。实验方法首先涉及综合 模型复合体设计用于探测结构、磁性、 双氧水的光谱性质，特别是化学性质 多核核心的分辨率比可能的高 蛋白质。双核配体的设计与构筑 在这个阶段具有特别重要的意义。新的建筑群已经完全建成 以包括X射线在内的物理测量为特征的 结晶学、电子自旋共振或核磁共振、拉曼、红外、 紫外可见光谱和穆斯堡尔谱学 测量，以及它们相对于特定的化学反应 蛋白质的功能。以便于比较生物无机物 化学，选定蛋白质的平行研究，特别是MMO 和RR，将进行，目标是提供详细的 结构信息，以了解辅因子相互作用，以及 要了解蛋白质环境如何调节反应 双铁中心的化学。虽然重点主要放在 铁，相关双核铜锰络合物的研究 将会继续。

The major objective of this research is to elucidate chemical and physical properties of ligand-bridged bimetallic and polymetallic centers in proteins and related model compounds. Attention will focus on diiron oxo proteins hemerythrin (Hr), methane monooxygen- ase (MMO), ribonucleotide reductase (RR) and purple acid phosphatase (PAP) and on the iron storage protein ferritin (Ft). Among the specific aims are to build binuclear iron molecules capable of reversible 02 binding and catalysis of hydrocarbon oxidation by 02, to characterize structurally and spectroscopically and to model the diiron center in MMO's, and to construct new polyiron oxo complexes as ferritin core models. An important goal is to discover fundamental relationships between structure and function. What features of the coordination chemistry of geometrically similar binuclear iron centers promote reversible 02 binding in Hr, reduction of ribo- to deoxyribonucleotides in RR, methane oxidation in MMO, and phosphate ester hydrolysis in PAP? What reactions control the iron oxo oligomerization steps that lead to the assembly of the polyiron core in Ft? The answers to these questions have many health-related implications. RR catalyzes the first committed step in DNA biosynthesis, and agents that inhibit its function have chemotherapeutic potential as antitumor and antiviral drugs. The preparation of new oxygen transport molecules could assist the development of artificial blood substitutes. Understanding how hydrolytic polymerization reactions of iron are controlled could lead to better management of its biological toxicities. The experimental approach involves first the synthesis of model complexes designed to probe structural, magnetic, spectroscopic and, especially, chemical properties of the di- or polynuclear cores at higher resolution than may be possible with the proteins. The design and construction of binucleating ligands is of specific importance in this stage. New complexes are fully characterized by physical measurements including X-ray crystallography, ESR or NMR magnetic resonance, Raman, infrared, UV-vis, and Mossbauer spectroscopy, by magnetic susceptibility measurements, and by their chemical reactions relative to specific protein functions. To facilitate comparative bioinorganic chemistry, parallel studies of selected proteins, specifically MMO and RR, will be carried out, the goals being to provide detailed structural information, to understand cofactor interactions, and to learn how the protein environment modulates the reaction chemistry of the diiron centers. While the focus is primarily on iron, studies of related binuclear copper and manganese complexes will be continued.