Substrate Modification at Redox Active Copper Centers

描述（由申请人提供）：本提案中概述的研究旨在了解在多巴胺β羟化酶和肽甘氨酸α羟化单加氧酶的铜中心发生的基本化学反应。这两种酶都含有两个结构上分离和光谱上不同的铜中心，并使用双氧作为唯一氧化剂催化碳氢化合物底物的羟基化。合成模型将模仿这两个中心。将制备的一系列模型是一个单核细胞铜中心，旨在模拟金属中心的反应性质，金属中心被认为是碳氢化合物羟基化通过假想的cuii -氢过氧中间体发生的位置。将进行研究以阐明这种铜中心模拟物氧化底物的机制。双核模型将包含两个铜引用的模拟物，双核配合物的研究将旨在了解两个中心如何协同工作以产生cuii -氢过氧物质。

DESCRIPTION (provided by applicant): The research outlined in this proposal is aimed at understanding the fundamental chemistry taking place at the copper-centers of Dopamine Beta Hydroxylase and Peptideglycine alpha Hydroxylating Monooxygenase. Both enzymes contain two structurally isolated and spectroscopically distinct copper centers and catalyze the hydroxylation of hydrocarbon substrates using dioxygen as the sole oxidant. Synthetic models will be made to mimic both of these centers. One series of models that will be prepared is a mononuctear copper center aimed at mimicking the reactive properties of the metal-center that is proposed to be the site where hydrocarbon hydroxylation takes place through a supposed CuII-hydroperoxo intermediate. Studies will be performed to elucidate the mechanism of substrate oxidation by this copper-center mimic. Dinuclear models will be made containing mimics for both copper-cites, Studies with the dinuclear complexes will be aimed at understanding how the two centers work in concert to generate the CuII-hydroperoxo species.