Oxidase vs. Oxygenase in Cu-Catalyzed Aerobic Oxidation of Phenolic Substrate

铜催化酚类底物有氧氧化中的氧化酶与加氧酶

• 批准号: 9111675
• 负责人: Scott D McCann
• 金额: $ 3.1万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-15 至 2018-07-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9111675
• 关键词: Aerobic; Aldehydes; Amines; Benign; Biochemical; Biochemical Process; Biological; Biomimetics; Catalysis; Chemicals; Chemistry; Competence; Copper; Coupling; Data; Development; Disease; Eating; Electron Spin Resonance Spectroscopy; Electron Transport; Enzymes; Exhibits; Family; Healthcare Systems; Hydroquinones; In Situ; Kinetics; Laws; Lead; Malignant Neoplasms; Mediator of activation protein; Metals; Methods; Minor; Mitomycins; Modeling; Molecular; Monophenol Monooxygenase; Naphthols; Naphthoquinones; Natural Products; Nature; Oxidants; Oxidases; Oxidation-Reduction; Oxygen; Oxygenases; Pathway interactions; Pharmaceutical Preparations; Pharmacologic Substance; Phenols; Plastoquinone; Play; Prevention; Process; Property; Quinones; Reaction; Research; Rest; Role; Route; Spectrum Analysis; Structure; System; Techniques; Testing; Therapeutic; Transition Elements; Water; Work; adduct; base; catalyst; chemical kinetics; cold temperature; design; diamino oxhydrase; functional group; insight; molecular sieving; oxidation; photosystem II; public health relevance; semiquinone; spectroscopic survey

 DESCRIPTION (provided by applicant): Phenols, hydroquinones, quinones and related compounds are common intermediates and products of various biochemical and chemical synthetic pathways. These compounds can be generated via enzymatic aerobic oxidation of organic precursors in biochemical systems; however, analogous chemical methods for aerobic oxidation remain challenging. The quinone motif is an important structure in many natural products and therapeutics. For example, the natural product mitomycin C is a prominent example of a family of quinone-containing therapeutics that exhibit potent anti-cancer properties. Quinones also play an important role as redox mediators in many biochemical processes. Plastoquinone is an example that facilitates electron-transfer processes associated with the oxidation of water to molecular oxygen in Photosystem II, and topaquinone catalyzes the oxidation of primary amines to aldehydes in copper amine oxidases. Hydroquinones and quinones can be generated selectively by aerobic oxidation of phenol precursors in Nature by the copper-containing enzyme tyrosinase; however, selective oxidation of phenols by chemical catalysts is rare. Oxygenase reactivity produces hydroquinones and quinones from phenols, while oxidase reactivity generates biphenols from phenols. Most non-enzymatic reaction conditions produce a mixture of these products. Elucidation of mechanistic principles that enable selective functionalization of phenols could have important impact. Recent synthetic advances suggest that Cu-catalyzed aerobic oxidation of phenols can switch between oxygenase and oxidase reactivity, and these systems provide ideal models for probing the mechanistic basis for the change in selectivity. The proposed research will interrogate the mechanism of phenol and naphthol oxidation reactions that appear to involve cooperative redox catalysis between Cu and quinone centers that resembles copper amine oxidases. The mechanistic approach will involve the determination of the catalytic reaction mechanisms of Cu oxidase and Cu oxygenase reactions of phenolic substrates. Several plausible catalytic intermediates will be prepared (e.g., CuII/semiquinone species) and these species will be tested for chemical and kinetic competence under the catalytic reaction conditions. A variety of spectroscopic techniques (e.g., UV-visible spectroscopy, electron paramagnetic resonance spectroscopy) will be used to identify the catalyst resting state species. The identity of the resting state, together with kinetic rate law data should enable identification of the turnover-limiting step, and the collective insights should illuminate the origin of oxygenase vs. oxidase reactivity. Ultimately, it is anticipated that the results of this work will allow for mechanisticaly guided design of new catalytic reactions.

 描述（由申请人提供）：酚类、对苯二酚类、醌类及相关化合物是各种生化和化学合成途径的常见中间体和产物。这些化合物可以通过生物化学系统中有机前体的酶促有氧氧化产生;然而，用于有氧氧化的类似化学方法仍然具有挑战性。醌基序是许多天然产物和治疗药物中的重要结构。例如，天然产物丝裂霉素C是显示出有效抗癌特性的含醌治疗剂家族的突出实例。醌类化合物在许多生物化学过程中作为氧化还原介质也起着重要的作用。质体醌是促进与光系统II中水氧化成分子氧相关的电子转移过程的一个例子，而托醌催化铜胺氧化酶中伯胺氧化成醛。对苯二酚和醌类化合物可以在自然界中通过含铜的酪氨酸酶对苯酚前体进行有氧氧化而选择性地产生;然而，通过化学催化剂对苯酚进行选择性氧化的情况很少。加氧酶反应性从酚产生氢醌和醌，而氧化酶反应性从酚产生联酚。大多数非酶促反应条件产生这些产物的混合物。阐明使酚类选择性官能化的机械原理可能具有重要影响。最近的合成进展表明，铜催化的酚类有氧氧化可以在加氧酶和氧化酶反应性之间切换，这些系统为探索选择性变化的机理基础提供了理想的模型。拟议的研究将询问苯酚和萘酚氧化反应的机制，这些反应似乎涉及铜和醌中心之间的协同氧化还原催化，类似于铜胺氧化酶。机理的方法将涉及确定的催化反应机制的铜氧化酶和铜加氧酶反应的酚类底物。将制备几种合理的催化中间体（例如，CuII/半醌类），并将在催化反应条件下测试这些物质的化学和动力学能力。各种光谱技术（例如，紫外-可见光谱法、电子顺磁共振光谱法）将用于鉴别催化剂静止状态物质。静止状态的身份，连同动力学速率定律数据应能够识别的营业额限制的步骤，和集体的见解应该照亮的起源加氧酶与氧化酶的反应性。最终，预计这项工作的结果将允许新的催化反应的机械引导设计。