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阐明激活O2的单核、双核和三核铜酶的关键反应步骤的机理。所使用的方法是合成的类似物的方法的活性位点的金属生物分子，从而低分子量的复合物的合成和检查在小分子水平的细节，以揭示从蛋白质基质的影响解耦的固有特性。如果适当关注连接环境，合成的铜络合物可以提供生物反应的机理细节。适当的连接可以引发特定的化学反应性，同时排除在均匀溶液中新生Cu-O2中间体的有害双分子反应。创建一个机械忠实和光谱一致的模型提供了一个特定的氧化机制，可以在一个小分子水平的细节检查化学先例。 .结构，光谱和反应特性的[（LPDA）铜（MeCN）]1+-O2产品使用简单的全烷基化二胺配体，L PDA，将提供化学优先级为可能的生物Cu-O2中间体和光谱基准，这些中间体可以被识别。 .双核铜酶酪氨酸酶的光谱全等模型显示酚单加氧酶的反应类似的酶。光谱和动力学研究的捕获反应中间体将提供一个更完整的机制，这是在黑色素生产的第一步反应的理解。 .假定的酪氨酸酶活性氧化剂（Cu II-O2，P）可能与等电子物质（Cu III-O2，O）平衡。定义每种异构体的反应行为将解决一个首要问题，即铜的3+氧化态在双核铜位点中是否具有生物学相关性。 .半乳糖氧化酶（GOase）的光谱和功能模型将探测Cuphenoxyl物种的化学反应性。 .一个结构确定的三核铜配合物将光谱和磁性特征类似的天然中间体的多铜氧化酶。铜蓝蛋白是人体血液中主要的含铜酶，是一种多铜氧化酶，参与铁的运输（铁氧化酶活性）。

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).