MODELING ENZYME DIMETALLIC CENTERS WITH CRYPTATE LIGANDS

这项研究计划概述了新型加密配体的合成，这些配体结合了硫酸盐结合部位，旨在将两个金属离子结合在不同但位置紧密的空腔中。直接目的是用这些隐形配体制备二铜络合物，以模拟细胞色素c氧化酶和一氧化二氮还原酶中已知存在的二铜氧化还原中心(CUA位点)。定义CuA位置的性质是可逆的电化学和完全离域的CuI-CuII混合价态。后一特征可能与金属与金属之间的短间隔有关，约2.5埃单位，这被一些人解释为表明金属与金属之间的直接键合作用。值得注意的是，这是第一次涉及金属-金属键的生物存在的双金属实体，因此有必要从理论上详细了解CUA位置的性质。根据这一目的，制备具有本文所述的新型含硫酸盐的加密配体的双铜络合物将有助于确定功能性CUA位点所需的特征。加密配体的设计允许金属施主原子的数量和类型的变化，以及调整不同的金属离子结合口袋之间的间隔。这些方面的每一个方面的差异将允许单独评估它们对CUA站点的重要性。再加上对这些模型化合物的理论成键分析，这些合成研究将更准确地描述CUA中心的性质。更广泛地说，成功地使用加密配体结合两个金属离子将使这些配体对模拟其他酶双金属位点具有吸引力。这些密码可能允许制备双核结构，否则很难用简单的配体制备。最终，新的双金属结构类型与生物相关类型的给体配体的合成可能提供特定的光谱标准，从而有助于在新的金属酶中识别这种结构。通过比较简单的无机类似物的性质，可以极大地帮助鉴定新金属酶中的金属中心。

This research proposal outlines the synthesis of novel cryptand ligands which incorporate thiolate binding sites and which are designed to bind two metal ions in distinct but closely positioned cavities. The immediate purpose is the preparation of dicopper complexes with these cryptate ligands to simulate the dicopper redox center (CuA site) known to exist in the enzymes cytochrome c oxidase and nitrous oxide reductase. Defining properties of the CuA site are reversible electrochemistry and a fully delocalized CuI-CuII mixed valent state. The latter feature may be related to the short metal-metal separation of approximately 2.5 Angstrom units, which has been interpreted by some as indicating a direct metal-metal bonding interaction. Significantly, this claim is the first for a biologically occurring dimetallic entity involving a metal-metal bond, and as such a detailed theoretical understanding of the nature of the CuA site is warranted. Pursuant to this end, the preparation of dicopper complexes with the novel thiolate-containing cryptand ligands described herein will help to ascertain the features requisite for a functional CuA site. The cryptate ligand design is such as to permit variation in the number and type of donor atoms to the metals as well as adjustment of the separation between the distinct metal ion binding pockets. Variations in each of these aspects will permit separate assessment of their importance to the CuA site. Coupled with a theoretical bonding analysis of these model compounds, these synthetic studies will yield a more accurate description of the nature of the CuA center. More generally, the successful use of cryptands to bind two metal ions will make these ligands attractive for modeling other enzyme dimetallic sites. These cryptands may permit preparation of dinuclear structures which are otherwise difficult to prepare with simple ligands. Ultimately, the synthesis of new dimetallic structure types with biologically relevant types of donor ligands may provide specific spectroscopic criteria whereby the recognition of such structure in new metalloenzymes will be facilitated. Identification of the metal centers in new metalloenzymes is greatly aided by comparison to the properties of simple inorganic analogues.