SYNTHETIC MODELS OF IRON SITES IN BIOLOGICAL SYSTEMS

这项研究计划的主要主题是开发系统 和合理的策略来合成含有以下化合物的模型配合物 一个、两个或多个由简单配体如氧化物桥联的铁离子 氢氧化物、水和/或羧酸盐。这些综合体将作为 非血红素铁中心的结构、电子和功能模型 生物系统和一般铁氧聚合过程，在 以便更好地了解铁在自然界中的关键作用。 应特别注意铁(II)的相互作用 与氧气的络合物。铁在氧气中起着至关重要的作用 电子转移反应和许多酶过程 包括那些参与DNA合成的基因。其他铁(二) 络合物利用其对氧的激活作用作为抗癌药物 攻击DNA，从而理解病毒的形成和功能 这些铁中心和铁的储存对健康是必不可少的。 扰乱铁在所有不同角色中的有效利用 许多疾病的致病因素。例如，像阿司匹林这样的药物会相互作用 有了铁酶切位点，并对 铁与氧的配位化学和反应性将有助于 这类药物的设计。 对化学这一探索性领域的系统方法包括 第一，多种铁(II)的分离和表征 单核和多核配合物；它们的相互转化和 与氧气相互作用生成多核铁(III)氧 集合体。第二代配基系统将被开发， 更接近地模拟实际的金属蛋白环境 分子识别概念的运用和分子识别的形成 超分子络合物。这些复合体更接近于 蛋白质环境的微妙决定了不同的 铁(II)与氧气的相互作用这种与氧气的相互作用 模拟了许多关键的生物功能-从各种功能到 可逆的氧气向底物的传输(碳氢化合物 羟基化)和自由基生成(DNA合成)。循序渐进 这些聚集体的形成随后在相同程度上被确定 尽可能详细，以便得出支配金属的原则 集合体的形成。铁在铁中的聚集过程 储藏蛋白铁蛋白特别令人关注，并正在 从两个方向靠近，聚集体中只有单一的氧 桥是涉及的，而那些双齿羧酸盐和 磷酸基团起着结构性的作用。物理化学技术 依赖于表征新材料的是X射线结晶学，1H 核磁共振、电子顺磁共振、紫外-可见光谱、穆斯堡尔谱和磁性。 应特别注意对13C和 与这些顺磁性化合物结合的羧酸盐和叠氮化合物的~(15)N核磁共振谱 络合物作为解释蛋白质结构和蛋白质的潜在工具 功能。了解这些定义良好的模型的属性 化合物极大地加速了对物理性质的解释 金属蛋白。

The governing theme of this research program is to develop systematic and rational strategies for the synthesis of model complexes containing one, two or more iron ions bridged by simple ligands such as oxide hydroxide, water, and/or carboxylates. These complexes are to serve as structural, electronic and functional models of non-heme iron centers in biological systems and of general iron-oxo aggregation processes, in order to better understand the critical role of iron in Nature. Particular attention is to be placed on the interaction of iron(II) complexes with dioxygen. Iron plays a crucial role in dioxygen and electron transfer reactions as well as many enzymatic processes including those involved in the synthesis of DNA. Other iron(II) complexes act as anti-cancer drugs by using their activation of dioxygen to attack DNA, thus an understanding of the formation and function of these iron centers and the storage of iron is essential for health. Disruption of the efficient usage of iron in all its diverse roles leads to a number of diseases. Drugs such as aspirin, for example, interact with iron enzymatic sites and a more complete understanding of the coordination chemistry and reactivity of iron with oxygen will aid in the design of such drugs. The systematic approach to this exploratory area of chemistry involves first the isolation and characterization of a variety of iron(II) mononuclear and multinuclear complexes; their interconversions and interactions with dioxygen to form multinuclear iron(III) oxo aggregates. A second generation of ligand system is to be developed that more closely mimics the actual metalloprotein environment through the utilization of concepts of molecular recognition and the formation of supramolecular complexes. These complexes more closely mimic the subtleties of the protein environment that dictate the varied interaction of iron(II) with dioxygen. This interaction with dioxygen models a number of crucial biological functions - as diverse as reversible dioxygen transport, to substrate oxidation (hydrocarbon hydroxylation) and radical generation (DNA synthesis). The stepwise formation of these aggregates is subsequently determined in as much detail as possible in order to arrive at principles which govern metal aggregate formation. The iron aggregation processes within the iron storage protein ferritin are of particular concern and are being approached from two directions, aggregates where only single oxygen bridges are involved and those in which bidentate carboxylate and phosphate groups play a structural role. Physicochemical techniques relied upon to characterize new materials are X-ray crystallography, 1H NMR, EPR, UV-Vis spectroscopies and Mossbauer and magnetic properties. Specific attention is to be placed on the interpretation of the 13C and 15N NMR spectra of carboxylates and azide bound to these paramagnetic complexes as potential tool for the elucidation of protein structure and function. Understanding the properties of these well defined model compounds greatly accelerates the interpretation of physical properties of metalloproteins.