Cu Dioxygen Reactivity in Small Molecule Complexes

小分子配合物中的 Cu 分子氧反应性

• 批准号: 7216907
• 负责人: T DANIEL STACK
• 金额: $ 29.62万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7216907
• 关键词: Active Sites; Address; Anions; Attention; Behavior; Benchmarking; Biological; Blood; Ceruloplasmin; Chemicals; Classification; Complex; Condition; Copper; Diamines; Dioxygen; Electronics; Environment; Enzymes; Equilibrium; Galactose Oxidase; Glycol; Goals; Grant; Human; Iron; Isomerism; Isotopes; Kinetics; Lactones; Ligands; Ligation; Melanins; Methodology; Mixed Function Oxygenases; Modeling; Molecular Weight; Mono-S; Monophenol Monooxygenase; Nature; Nuclear; Oxidants; Positioning Attribute; Production; Property; Proteins; Reaction; Reagent; Research; Role; Site; Solutions; Solvents; Structure; System; Time; Variant; Work; alcohol oxidase; analog; aqueous; cold temperature; copper oxidase; design; extreme temperature; insight; interest; oxidation; parity; phenolate; small molecule; trafficking

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).

描述（由申请人提供）：我们研究的广泛和长期目标是对激活O2的单核和三核铜酶的关键反应步骤的机械阐明。所使用的方法是对金属生物分子的活性位点的合成模拟方法的方法，从而在小分子的细节水平上合成和检查低分子量复合物，以揭示与蛋白质基质影响的固有特性。合成铜络合物可以提供生物反应的机理细节，如果适当注意结扎环境。适当的连接可以引起特定的化学反应性，同时排除同质溶液中新生Cu-O2中间体的有害双分子反应。创建机械忠实和光谱镜的模型的创建为特定的氧化机制提供了化学先例，该机制可以在细分较小的细节水平上进行检查。 。 [（LPDA）CUL（MECN）] 1+-O2产物的结构，光谱和反应性表征使用简单的甲基化二胺二氨酸，L PDA，将为可能的生物学Cu-O2中间体和光谱基准提供化学优先级，并通过该基准可以通过该中间体可以鉴定出这种中间体。 。双核铜酶酪氨酸酶的光谱一致模型表现出类似于酶的苯基单氧酶反应性。捕获反应中间体的光谱和动力学研究将对这种反应提供更完整的机械理解，这是黑色素产生的第一步。 。假定的酪氨酸酶活性氧化剂（Cu ll-O2，P）可能与等电体物种（Cu Ill-02，O）处于平衡状态。定义每个异构体的反应性行为将解决一个总体问题，即铜的3+氧化状态是否在双核铜部位具有生物学相关。 。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。 。结构定义的三核铜络合物将在光谱和磁性上具有类似于多铜氧化酶中天然中间体的特征。 Ceruloplasmin是人类血液中主要含铜的酶，是一种多碳酸氧化酶，参与了铁（铁氧化酶活性）。