SYNTHESIS OF MODEL COMPLEXES FOR NITRILE HYDRATASE

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 腈水合酶（Nitrile hydratase，简称NHase）是一种存在于土壤细菌中的酶，催化有机腈转化为有机酰胺。各种腈水合酶在活性位点具有铁或钴原子。这些酶是不寻常的，因为活性位点金属存在于由酰胺氮原子和氧化硫原子组成的N2 S3配位环境中。该项目涉及“模型复合物”的合成，该复合物将密切模仿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有效地进行化学反应所需的特征，并有可能开发出能够重现甚至改善这种反应性的合成系统。这些研究是重要的，不仅为他们将提供有关的催化机制的腈水合酶的信息，但也为信息，可适用于其他金属酶具有类似的活性位点的功能。我们已经在结构上表征了第一个钴络合物，其具有与钴结合的两个氮原子和三个硫原子，再现了与天然酶中的钴结合的原子类型。这种复合物含有亚胺氮，而不是酶中的酰胺氮。我们还制备了一个相关的模型配合物，其中包括酰胺氮和氧化硫。对这些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.