Cu Dioxygen Reactivity in Small Molecule Complexes

描述(由申请人提供)：我们研究的广泛和长期目标是从机理上阐明激活O2的单核、二核和三核铜酶的关键反应步骤。所使用的方法是合成模拟方法来确定金属生物分子的活性部位，从而合成低分子化合物并在小分子细节水平上进行检查，以揭示不受蛋白质基质影响的内在性质。如果对连接环境给予适当的关注，合成的铜配合物可以提供生物反应的机理细节。适当的连接可以引起特殊的化学反应，同时排除在均相溶液中新生的铜-O2中间体的有害的双分子反应。力学上忠实的和光谱上一致的模型的创建为可以在小分子细节水平上研究的特定氧化机制提供了化学先例。 。使用简单的全烷基二胺配体L PDA对[(LPDA)CuL(MeCN)]1+-O2产物的结构、光谱和反应活性进行表征，将为可能的生物铜-O2中间体和光谱基准提供化学优先权，从而可以识别此类中间体。 。双核铜酶酪氨酸酶的光谱一致性模型显示出与该酶类似的酚单加氧酶活性。对捕获的反应中间体的光谱和动力学研究将提供对该反应的更完整的机理理解，这是黑色素产生的第一步。 。推测的酪氨酸酶活性氧化剂(Cu11-O2，P)可能与一个等电子物种(CuIll-02，O)处于平衡状态。定义每个异构体的反应行为将解决一个首要问题，即铜的3+氧化状态是否与双核铜位的生物相关。 。半乳糖氧化酶(GOase)的光谱和功能模型将探索铜氧基物种的化学反应活性。 。将对结构定义的三核铜配合物进行光谱和磁性表征，以获得类似于多铜氧化酶酶中天然中间体的特征。铜蓝蛋白是人类血液中主要的含铜酶，是一种多铜氧化酶，参与铁的运输(亚铁氧基酶活性)。

DESCRIPTION (provided by applicant): The broad and long-term objective of our research is the mechanistic elucidation of key reaction steps of mono- di- and tri-nuclear copper enzymes that activate O2. The methodology used is that of the synthetic analog approach to the active sites of metallobiomolecules, whereby low molecular weight complexes are synthesized and examined at a small molecule level of detail to reveal intrinsic properties uncoupled from the influences of the protein matrix. Synthetic copper complexes can provide mechanistic details of biological reactions if appropriate attention is directed to the ligation environment. Appropriate ligation can elicit particular chemical reactivity while precluding deleterious bimolecular reactions of nascent Cu-O2 intermediates in a homogenous solution. Creation of a mechanistically faithful and a spectroscopically congruent model provides chemical precedent for a particular oxidative mechanism that can be examined at a small molecule level of detail. . Structural, spectroscopic and reactivity characterization of [(LPDA)Cul(MeCN)]1+-O2 products using simple peralkylated diamine ligands, L PDA, will provide chemical precedence for possible biological Cu-O2 intermediates and spectroscopic benchmarks by which such intermediates may be identified. . Spectroscopically congruent models of the binuclear copper enzyme tyrosinase display phenolate monooxygenase reactivity similar to the enzyme. Spectroscopic and kinetic studies of trapped reaction intermediates will provide a more complete mechanistic understanding of this reaction that is the first step in melanin production. . The postulated tyrosinase active oxidant (Cu ll-O2, P) is potentially in equilibrium with an isoelectronic species (Cu Ill- 02, O). Defining the reactivity behavior of each isomer will address an overarching question of whether the 3+ oxidation state of copper is biologically relevant in binuclear copper sites. . Spectroscopic and functional models of galactose oxidase (GOase) will probe the chemical reactivity of Cuphenoxyl species. . A structurally defined trinuclear copper complex will be spectroscopically and magnetically characterized for features similar to the native intermediate in the multi-copper oxidase enzymes. Ceruloplasmin, the major copper-containing enzyme in human blood, is a multi-copper oxidase that is involved in the trafficking of iron (ferroxidase activity).