LIGAND BRIDGED BINUCLEAR METAL COMPLEXES AND PROTEINS

这项研究的主要目的是阐明化学和 配体桥连金属和多金属的物理性质 蛋白质和相关模型化合物的中心。 注意力将 重点研究二铁氧蛋白血红蛋白（Hr）、甲烷单氧- 酶（MMO）、核糖核苷酸还原酶（RR）和紫酸 磷酸酶（PAP）和铁储存蛋白铁蛋白（Ft）。 具体目标之一是建造双核铁分子 能够可逆的O2结合和烃的催化 通过O2氧化，以在结构和光谱上表征 并模拟MMO中的二铁中心，并构建新的 作为铁蛋白核心模型的聚铁氧代络合物。 一个重要目标 是为了发现结构和 功能 的配位化学有什么特点 几何相似的双核铁中心促进可逆02 Hr中的结合，RR中核糖核苷酸还原为脱氧核糖核苷酸， 甲烷氧化在MMO，和磷酸酯水解在PAP？ 什么反应控制铁氧低聚步骤，导致 到组装的聚铁芯在英尺？ 的答案 这些问题有许多与健康有关的含义。 RR催化 DNA生物合成的第一个关键步骤，以及抑制 其功能具有抗肿瘤化疗潜力， 抗病毒药物 新型氧转运分子的制备 可以帮助人造血液替代品的发展。 了解铁的水解聚合反应是如何 控制可能会导致更好地管理其生物 毒性 实验方法首先涉及合成 设计来探测结构，磁性， 光谱，特别是化学性质的二或 多核岩心的分辨率可能高于 蛋白质 双核配体的设计与构建 在这个阶段特别重要。 新的综合体完全 通过包括X射线在内的物理测量来表征 结晶学、ESR或NMR磁共振、拉曼、红外、 紫外-可见光谱和穆斯堡尔光谱，通过磁化率 测量，并通过它们的化学反应相对于特定的 蛋白质功能 为了便于比较生物无机 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， 了解蛋白质环境如何调节反应 二铁中心的化学性质。 虽然重点主要放在 铁的双核铜锰配合物的研究 将继续进行。

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.