SYNTHESIS OF MODEL COMPLEXES FOR NITRILE HYDRATASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 腈水合酶(NHase)是在土壤细菌中发现的一种催化有机腈转化为有机酰胺的酶活性。各种氰基水合酶的活性部位都有铁原子或钴原子。这些酶的不同寻常之处在于，活性中心金属位于由酰胺氮原子和氧化硫原子组成的N2S3配位环境中。这个项目包括合成“模型络合物”，它将密切模拟酶的铁或钴中心的直接结构。通过研究这些络合物的结构、光谱和反应性，将有可能确定铁或钴原子需要什么特征才能有效地进行化学操作，并有可能开发能够重现甚至改进这种反应性的合成系统。这些研究不仅对于它们将提供关于NHase催化机制的信息是重要的，而且对于可以应用于具有类似活性中心特征的其他金属酶的信息也是重要的。我们已经在结构上表征了第一个钴配合物，它有两个氮原子和三个硫原子与钴结合，再现了天然酶中与钴结合的原子类型。这种复合体含有亚胺氮，而不是酶中的酰胺氮。我们还制备了含有酰胺氮和氧化硫的相关模型络合物。对这些模型和相关模型的催化活性的进一步研究将解决这些特征的重要性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Nitrile hydratase (NHase) is an enzyme activity found in a number of soil bacteria which catalyzes conversion of organic nitriles to organic amides. Various nitrile hydratase enzymes have either an iron or cobalt atom present at the active site. These enzymes are unusual in that the active site metal resides in an N2S3 coordination environment comprised of amide nitrogen atoms and oxidized sulfur atoms. This project involves the synthesis of "model complexes" which will closely mimic the immediate structure of the iron or cobalt centers of the enzyme. By studying the structures, spectroscopy, and reactivity of these complexes it will be possible to determine what features are required for the iron or cobalt atom to effectively carry out the chemistry and potentially to develop synthetic systems which will be able to reproduce or even improve upon this reactivity. These studies are important not only for the information they will provide regarding the catalytic mechanism of NHase, but also for information that can be applied to other metalloenzymes with similar active-site features. We have structurally characterized the first cobalt complex which has two nitrogen and three sulfur atoms bound to the cobalt, reproducing the types of atoms that are bound to the cobalt in the native enzyme. This complex contains imine nitrogens, rather than the amide nitrogens in the enzyme. We have also prepared a related model complex which incorporates amide nitrogens and oxidized sulfurs. Further studies on the catalytic activity of these and related models will address the importance of these features.