Molybdenum Pterin-Dithiolene Complexes for Model Studies of the Catalytic Site of

描述（由申请人提供）：钼与健康的关系远不如熟悉的必需金属铁、铜和锌为公众所熟知。然而，罕见的遗传性疾病导致受损的钼酶导致普遍的神经系统问题，在最好的情况下，在最坏的情况下是致命的。不仅是人类，地球上几乎所有生物都依赖于一种或多种钼或钨酶。钼酶在各种复杂程度的生命中都扮演着如此重要的角色，是碳、氮和硫元素全球地球化学循环的关键参与者。尽管研究界在了解钼和钨酶方面取得了巨大进展，但对钼和钨酶共同的特殊配体的作用了解甚少。这种配体，昵称为蝶呤，是一种蝶呤取代的二硫纶螯合物，在所有生物化学中是独一无二的。虽然已经了解了很多关于为什么二硫纶螯合物适合于由这些酶的金属催化的电子转移反应，蝶呤取代基的要求在很大程度上仍然是个谜。新的模型，是这个项目的重点，将二硫纶螯合物附加的蝶呤，这两个关键功能的蝶呤在所有钼和W酶，因此将是独特的，他们的潜力，研究范围的蝶呤氧化还原化学的蝶呤取代的二硫纶配体协调钼。该项目旨在详细了解蝶呤-二硫杂环戊烯结构的独特方面，这些方面影响钼的反应性和协调蝶呤-二硫杂环戊烯配体本身的反应性。具体目标是：（a）通过化学和电化学方法探索钼配位的蝶呤-二硫杂环戊烯的氧化还原行为;（B）探测蝶呤在不同还原水平下对钼-二硫杂环戊烯单元的电子效应;（c）完成所有模型化合物的完整光谱和结构表征;（d）开始研究钼和铜之间的二硫杂环戊烯转移。所提出的工作的结果需要在理解人类代谢过程中钼酶的功能和可能的功能障碍方面取得进一步进展。对这些电子结构与钼活性中心非常相似的模型的研究可望：（1）揭示蝶呤在所有钼多蝶呤酶活性中心的特殊作用; B）提供光谱和结构基准以帮助解释来自酶的类似结果，以及c）提供理解Mo和W酶的活性位点化学所需的基础化学的实例，可能为未来的治疗打下基础。钼与健康的关系远不如熟悉的基本金属铁，铜和锌为公众所知，但罕见的遗传性疾病导致钼酶受损，最好的情况下会导致普遍的神经系统问题，最坏的情况下会致命。最近，铜水平和钼酶之间的可能联系被发现。该项目的目标是获得一个更详细的了解如何独特的配体环境钼在辅酶酶是至关重要的酶的活性。

DESCRIPTION (provided by applicant): The relationship of molybdenum to health is far less well known by the general public than that of familiar essential metals iron, copper and zinc. Yet rare inherited diseases resulting in compromised molybdenum enzymes lead to pervasive neurological problems at best and are fatal at worst. Not only humans, but nearly every organism on this planet relies on one or more molybdenum or tungsten enzymes. Having such key roles for life at all levels of complexity, molybdenum enzymes are key participants in the global biogeochemical cycling of the elements carbon, nitrogen and sulfur. Despite huge progress made by the research community in understanding molybdenum and tungsten enzymes, very little is understood about the role of the special ligand common to both Mo and W enzymes. This ligand, nicknamed molybdopterin, is a pterin-substituted dithiolene chelate and is unique in all of biochemistry. While much has been learned about why a dithiolene chelate is suited for the electron transfer reactions catalyzed by the metals of these enzymes, the requirement of the pterin substituent remains largely a mystery. The new models that are the focus of this project incorporate a dithiolene chelate appended by a pterin, both of the key features of molybdopterin in all Mo and W enzymes, and therefore will be unique for their potential to study the gamut of pterin redox chemistry for a pterin-substituted dithiolene ligand coordinated to Mo. The proposed project seeks a detailed understanding of the unique aspects of the pterin-dithiolene structure that influence both the reactivity at molybdenum and within the coordinated pterin-dithiolene ligand itself. Specific objectives are: (a) explore the redox behavior of a molybdenum-coordinated pterin-dithiolene by chemical and electrochemical methods; (b) to probe the electronic effects of pterins at different levels of reduction on the Mo-dithiolene unit; (c) to accomplish full spectroscopic and structural characterization of all model compounds; (d) to begin an investigation of dithiolene transfer between molybdenum and copper. The results of the proposed work are needed to make further progress in understanding the function, and possibly the dysfunction, of the molybdenum enzymes in human metabolic processes. It is expected that studies of these models whose electronic structure closely resembles that of the molybdenum active site will: a) reveal the special purpose of the pterin in the active site of all molybdopterin enzymes; b) provide spectroscopic and structural benchmarks to aid interpretation of analogous results from the enzymes and c) provide examples of fundamental chemistry needed to understanding the active site chemistry of Mo and W enzymes, possibly laying groundwork for future therapies. The relationship of molybdenum to health is far less well known by the general public than that of familiar essential metals iron, copper and zinc, yet rare inherited diseases resulting in compromised molybdenum enzymes lead to pervasive neurological problems at best and are fatal at worst. More recently, a possible link between copper levels and molybdenum enzymes has been discovered. The goal of this project is to gain a more detailed understanding of how the unique ligand environment of molybdenum in molybdoenzymes is critical to the enzyme activity.