Synthetic Analogues of Cysteinate-Ligated Metalloenzymes

描述（由申请人提供）：腈水合酶（nase）和超氧化物还原酶（SOR）是一类新的非血红素铁酶，含有与铁配合的半胱氨酸硫。从使用nase的腈水合作用到使用SOR的超氧化物还原作用，它们的功能差别很大。虽然nase和SOR的结构已经确定，但关于这两种酶的作用机制仍有许多未解决的问题尚未得到充分解决。在这方面，本提案中描述的研究将侧重于模拟nase的反应性，以了解腈水解的机制以及肽酰胺和半胱氨酸硫配体在促进功能方面可能发挥的作用；确定氧合硫是否是nase活性所必需的，或者它们是否只是一个人工产物；理解和确定仅含氮供体的Pel - 11过氧化物的电子和反应性如何受到硫代硫的影响，并直接比较结构相关的模型体系之间的差异。为了实现这些目标，将合成不同的合成模型配合物并研究它们的反应性。

DESCRIPTION (provided by applicant): Nitrile hydratase (NHase) and superoxide reductase (SOR) are a new class of non-heme iron enzymes that contain cysteinate sulfurs coordinated to iron. Their function varies enormously from nitrile hydration, with NHases, to superoxide reduction, with SOR. Although the structures of NHase and SOR have been defined, a number of unresolved questions concerning the mechanisms of action of both enzymes have yet to be adequately addressed. To this regard, the research described in this proposal will focus on modeling the reactivity of NHase in an effort to understand the mechanism of nitrile hydrolysis as well as the role that peptide amides and cysteinate sulfur ligand(s) might play in promoting function; determining whether the oxygenated sulfurs are necessary for NHase activity, or whether they are simply an artifact; understanding and determining how the electronic and reactivity properties of Pel 11-peroxides containing only nitrogen donors are affected by the incorporation of a thiolate sulfur and make direct comparisons between structurally related model systems that differ by only one ligand. To achieve these goals, different synthetic model complexes will be synthesized and their reactivity studied.