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贝塔羟基酶和肽甘氨酸α羟化单加氧酶的铜中心发生的基本化学。这两种酶都含有两个结构上分离的和光谱上不同的铜中心，并以氧气为唯一氧化剂催化碳氢化合物底物的羟基化。将制作模拟这两个中心的合成模型。将准备的一系列模型是一个单核撕裂铜中心，旨在模拟金属中心的反应性质，该中心被认为是通过假定的CuII-氢过氧基中间体进行碳氢羟基化的位置。将进行研究，以阐明这种铜中心模拟物的底物氧化机理。将制作包含两个铜Cite的模拟的双核模型，对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-氢过氧基物种。

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.