Trapping reactive intermediates and their application towards catalysis

捕获反应中间体及其在催化中的应用

基本信息

批准号：
10586065
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
项目类别：
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/10586065
关键词：
3-Dimensional Address Bacteria Biological Process Carbon Catalysis Chemicals Chemistry Cobalt Complex Copper Crystallization Cytochrome P450 Cytochromes Development Electronics 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 Oxygen Particulate Pharmacologic Substance Population Porphyrins Process Productivity Property Reaction Reagent Relaxation Research Route Series Spectrum Analysis Steroids System Transition Elements Waste Management Waste Products adduct catalyst chemical synthesis electronic structure flexibility frontier functional group functional mimics improved insight metal complex molecular orbital monomer novel oxene oxidation small molecule theories trait

3-Dimensional Address Bacteria Biological Process Carbon Catalysis Chemicals Chemistry Cobalt Complex Copper Crystallization Cytochrome P450 Cytochromes Development Electronics 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 Oxygen Particulate Pharmacologic Substance Population Porphyrins Process Productivity Property Reaction Reagent Relaxation Research Route Series Spectrum Analysis Steroids System Transition Elements Waste Management Waste Products adduct catalyst chemical synthesis electronic structure flexibility frontier functional group functional mimics improved insight metal complex molecular orbital monomer novel oxene oxidation small molecule theories trait

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项目摘要

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.

项目摘要单加氧酶酶的家族用于执行氧化物组转移催化以广泛的驱动两个功能之一：（1）代谢碳氢化合物构建块（例如类固醇，脂肪酸）的废物 cytrohrome P450（CYPS）中的管理或马烯合成；（2）甲烷作为鞋底的利用碳和能源（即甲嗜营养细菌）。氧化酶之间的共同特征是通过电子调整其催化中心以实现氧气转移到可靠的C – H键底物的能力。适应电子结构调整原理以设计新的合成，并具有很好的催化剂承诺（1）了解酶系统如何通过发现什么反应序列来起作用可能是可能的，（2）开发出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键的合成和表征，金属稳定的自由基模拟生物单加氧酶的功能。单加糖酶利用金属类oxenoid配体驱动C-H键激活和C杂化键形成，提供了有关如何进行的蓝图模仿这种反应性。选择性地将功能合并到未激活的C – H键中的能力代表将廉价的化学饲料储备（例如烃）转化为增值方面的显着进步功能分子（例如药物前体）。为了实现这一目标，该提议概述了产生具有类oxenoid功能的金属配体多键合复合物并检查其反应化学与过渡金属和类氧配体氧化还原状态的关系。该建议旨在解决以下问题：（1）哪种过渡金属氧连接和随之而来的电子结构可以促进C-H 键羟基化学？（2）单体铜可以像末端的氧氧化配体一样建议反应性氧化物特别是甲烷单加氧酶？（4）功能组如何氧化态（即氧，氧基，氧烯）影响功能组转移催化剂？（5）金属稳定的配体可以通常，开发自由基来实现新的C-H键功能化催化？使用二吡啶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多键的策略在铁，钴，镍和铜上。提议一种空间抑制双吡啶的二吡啶是合成的理想选择，结晶和全光谱表征，cu类似于电势末端Cu（O）加合物特别是甲烷单加氧酶。拟议的更广泛的科学影响研究可以总结为以下：这项研究将改善该领域对因素的理解有助于促进生产性C – H键激活和功能化，进一步发展新的催化剂通过用最少的废物产物通过清洁反应路线合成增值商品化学物质。