IMPROVED MODEL COMPLEXES FOR MOLYBDOENZYME ACTIVE SITES

这个项目的目标是定义化学可能在 钼酶的活性位点。每一个生物体都依赖于一个或 更多的约四十已知钼酶的持续健康。 除了这些作用之外，钼酶是 碳、氮和硫元素的全球地球化学循环。的 这些酶的催化位点处的钼配位环境 最近由于X射线晶体结构而变得更加明确 几种酶的测定。然而，在一种情况下，二甲基亚砜 还原酶（DMSOR），Mo位点的定义变得更加混乱，因为 观察到三种不同的Mo配位环境。假说 提出了解释DMSOR活性位点结构之间的分歧， 球形红杆菌和两个独立的测定R。囊状的 显然需要改进的活性位点模型化合物来测试一些 这些假设。DMSOR活性中心的新模型化合物已经被发现， 开发这些模型的显著特点是， 与蝶呤取代基几乎相同的二硫杂环戊烯取代基， 酶。预期的结果是，这些模型将拥有 电子结构和化学反应性与酶非常相似 活性位点。这些模型对于建立反应性类型将是有价值的 并识别光谱特征以解释类似的结果 从钼酶。新的模型是由一个耦合综合 四硫化二铼试剂和带有四硫化二铼的炔之间的反应， N-杂环蝶呤或喹喔啉。得到了母体模型化合物 其中Mo处于形式+4氧化态，并获得Mo（V）和Mo（VI）化合物 化学氧化将被探索。将注意识别 与已知或怀疑的氧化反应相关的其他氧化产物 酶涉及N-杂环取代基的还原反应将 可以探索，既作为形成活性物质的吡喃环组分的手段， 以及重复应用于蛋白质的还原处理 被怀疑产生特殊活性部位结构的晶体 通过X射线衍射观察。预计这些模型的研究 其电子结构与钼活性中心的电子结构非常相似 将产生重大成果，将：a）提供基础， 了解DMSOR X射线结构的多样性; B）揭示了DMSOR X射线结构的特殊性。 蝶呤在所有蝶呤酶的活性位点中的用途; c） 提供光谱和结构基准，以帮助解释 来自酶的类似结果和d）提供了基本的 化学需要在理解活性位点化学方面取得进展， 钼和钨酶。

This project has the goal of defining the chemistry possible at the active sites of molybdenum enzymes. Every living organism relies on one or more of the approximately forty known molybdenum enzymes for sustained health. In addition to these roles, molybdenum enzymes are key participants in the global biogeochemical cycling of the elements carbon, nitrogen and sulfur. The molybdenum coordination environment at the catalytic sites of these enzymes has recently become more well-defined as a result of X-ray crystal structure determinations for several enzymes. However, in one case dimethylsulfoxide reductase (DMSOR), definition of the Mo site has become more confused because three different Mo coordination environments are observed. Hypotheses have been presented to explain the disagreement between DMSOR active site structures from Rhodobacter sphaeroides and two independent determinations of R. capsulatus. There is a clear need for improved active site model compounds to test some of these hypotheses. New model compounds for the active site of DMSOR have been developed. The distinctive feature of these models is the incorporation of dithiolene substituents that are nearly identical to the pterin substituent in the enzymes. The anticipated result is that these models will possess electronic structure and chemical reactivity very similar to that of the enzyme active sites. These models will be valuable for establishing reactivity types and identifying spectroscopic signatures for interpreting analogous results from the molybdenum enzymes. The new models are synthesized by a coupling reaction between a molybdenum-tetrasulfide reagent and an alkyne bearing the N-heterocycles pterin or quinoxaline. The parent model compounds are obtained with Mo in a formal +4 oxidation state and access to Mo(V) and Mo(VI) compounds by chemical oxidation will be explored. Attention will be given to identifying other oxidation products relevant to known or suspected oxidation reactions of the enzyme. Reduction reactions involving the N-heterocyclic substituents will be explored, both as a means to forming the pyran ring component of the active site as well as to duplicate the reduction treatment applied to protein crystals which is suspected to produce the peculiar active site structure observed by X-ray diffraction. It is expected that studies of these models whose electronic structure closely resembles that of the molybdenum active site will yield significant results that will: a) provide the basis for understanding the diversity of DMSOR X-ray structures; b) reveal the special purpose of the pterin in the active site of all molybdopterin enzymes; c) provide spectroscopic and structural benchmarks to aid in interpretation of analogous results from the enzymes and d) provide examples of fundamental chemistry needed to make progress in understanding the active site chemistry of molybdenum and tungsten enzymes.