Trapping reactive intermediates and their application towards catalysis

捕获反应中间体及其在催化中的应用

• 批准号: 10419401
• 负责人: Theodore A Betley
• 金额: $ 33.18万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10419401
• 关键词: 3-Dimensional; Address; Bacteria; Biological Process; Carbon; Catalysis; Chemicals; Chemistry; Cobalt; Complex; Copper; Crystallization; Cytochrome P450; Cytochromes; Development; Energy-Generating Resources; Enzymes; Family; Fatty Acids; Formulation; Generations; Goals; Hormones; Hydrocarbons; Hydrogen Bonding; Hydroxylation; Iron; Ligands; Magnetometries; Metals; Methane; Methane hydroxylase; Mixed Function Oxygenases; Modeling; Nickel; Oxidants; Oxidation-Reduction; Oxides; Oxygen; Particulate; Pharmacologic Substance; Population; Porphyrins; Process; Property; Reaction; Reagent; Research; Route; Series; Spectrum Analysis; Steroids; System; Transition Elements; Waste Management; Waste Products; adduct; base; catalyst; chemical synthesis; electronic structure; flexibility; frontier; functional group; functional mimics; improved; insight; metal complex; molecular orbital; novel; oxene; oxidation; small molecule; theories; trait

Project Summary The family of monooxygenase enzymes are utilized to perform oxidative group transfer catalysis to broadly drive one of two functions: (1) metabolize hydrocarbon building blocks (e.g., steroids, fatty acids) for waste management or hormone synthesis in cytrochrome P450 (CYPs); and (2) the utilization of methane as the sole carbon and energy source (i.e., methanotrophic bacteria). The common trait amongst the oxidizing enzymes is the ability to electronically tune their catalytic centers to achieve oxygen transfer to robust C–H bond substrates. Adapting the electronic structure tuning principles to devise new synthetic, abiological catalysts holds great promise to (1) understand how the enzymatic systems might function by uncovering what reaction sequences are possible, and (2) developing new catalytic reactions that mimic the reactivity of the monooxygenases. This proposal describes the synthesis and characterization of novel metal-ligand multiple-bonds and metal-stabilized radicals to mimic the function of biological monooxygenases. Monooxygenases utilize metal- oxenoid ligands to drive C−H bond activation and C−heteroatom bond formation, providing a blueprint on how to emulate this reactivity. The ability to selectively incorporate functionality into unactivated C–H bonds represents a significant advance in converting inexpensive chemical feed stocks (e.g. hydrocarbons) to value-added functional molecules (e.g., pharmaceutical precursors). To achieve this goal, this proposal outlines a strategy to generate metal-ligand multiply-bonded complexes featuring oxenoid functionalities and examine their reaction chemistry as a function of transition metal and oxenoid ligand redox state. This proposal seeks to address the following questions: (1) Which transition metal-oxo linkage and attendant electronic structure can facilitate C-H bond hydroxylation chemistry? (2) Can monomeric copper support a terminal oxo-like ligand as would be suggested for the reactive oxidant in particulate methane monooxygenases? (4) How do functional group oxidation states (i.e., oxo, oxyl, oxene) impact functional group transfer catalysis? (5) Can metal-stabilized ligand radicals in general be developed to enable new C-H bond functionalization catalysis? Using dipyrrin ligand platforms as truncated models of the porphyrin platform found in cytochrome monooxygenases, this proposal outlines a strategy to synthesize and characterize metal-ligand multiple bonds on iron, cobalt, nickel, and copper. A sterically encumbered dipyrrin is proposed to be ideal for the synthesis, crystallization, and full spectroscopic characterization of a terminal oxenoid adducts of Cu akin to the potential terminal Cu(O) adduct in particulate methane monooxygenase. The broader scientific impact of the proposed research can be summarized as the following: this study will improve the field’s understanding of factors contributing to the promotion of productive C–H bond activation and functionalization, further developing new catalysts to synthesize value-added, commodity chemicals via clean reaction routes with minimal waste product.

项目概要 单加氧酶家族用于进行氧化基团转移催化，广泛驱动 两种功能之一：(1) 代谢碳氢化合物构件（例如类固醇、脂肪酸）以产生废物 细胞色素 P450 (CYP) 的管理或激素合成； (2) 以甲烷为唯一能源 碳和能源（即甲烷氧化细菌）。氧化酶的共同特征是 能够以电子方式调节其催化中心，以实现氧转移到坚固的 C-H 键基质。 采用电子结构调整原理来设计新的合成非生物催化剂具有重要意义 承诺（1）通过揭示什么反应序列来了解酶系统如何发挥作用 是可能的，并且（2）开发模拟单加氧酶反应性的新催化反应。 该提案描述了新型金属配体多重键的合成和表征以及 金属稳定的自由基模仿生物单加氧酶的功能。单加氧酶利用金属- oxenoid配体驱动C−H键激活和C−杂原子键形成，提供了如何 模拟这种反应性。选择性地将功能性结合到未活化的 C-H 键中的能力代表 将廉价化学原料（例如碳氢化合物）转化为附加值方面的重大进步 功能分子（例如药物前体）。为了实现这一目标，本提案概述了一项战略 生成具有 oxenoid 功能的金属-配体多重键配合物并检查其反应 化学作为过渡金属和氧杂配体氧化还原态的函数。该提案旨在解决 以下问题：（1）哪种过渡金属-氧键和伴随的电子结构可以促进C-H 键羟基化化学？ (2) 单体铜可以支持末端氧代配体吗？ 建议用作颗粒甲烷单加氧酶中的活性氧化剂？ (4) 官能团如何 氧化态（即氧代、氧基、氧烯）影响官能团转移催化吗？ (5) 金属稳定配体 一般而言，自由基的开发是为了实现新的 C-H 键功能化催化吗？ 使用二吡啉配体平台作为细胞色素中发现的卟啉平台的截短模型 单加氧酶，该提案概述了合成和表征金属-配体多重键的策略 铁、钴、镍和铜。空间阻碍的二吡啉被认为是合成的理想选择， 类似于电位的 Cu 末端 oxenoid 加合物的结晶和全光谱表征 颗粒甲烷单加氧酶中的末端 Cu(O) 加合物。拟议的更广泛的科学影响 研究可概括如下：这项研究将提高该领域对因素的理解 有助于促进高效的C-H键活化和功能化，进一步开发新的 催化剂通过清洁的反应路线以最少的废物合成增值的商品化学品。