Mechanisms of Peroxyl Radical Addition Reactions

过氧自由基加成反应机理

基本信息

批准号：
1664851
负责人：
Libin Xu
金额：
$ 40.5万
依托单位：
University of Washington
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1664851&HistoricalAwards=false
关键词：
Mechanisms Peroxyl Radical Addition Reactions

项目摘要

In this project, funded by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Libin Xu of the Department of Medicinal Chemistry at the University of Washington aims to develop chemical tools to understand the reactivities and reaction mechanisms of oxidation of biologically important lipids. Understanding the fundamental chemistry underneath lipid peroxidation has broad impacts because lipid peroxidation plays significant roles in human pathologies, such as aging, atherosclerosis, and degenerative diseases. The project lies at the interface of physical organic chemistry and bioorganic chemistry and utilizes modern analytical chemistry techniques, and is well suited to the education of scientists with different training backgrounds. This research group also aims to integrate education with the research plan by disseminating the knowledge of lipid peroxidation through outreach to high school students and teachers and attracting undergraduates from diverse backgrounds to the research field. The rate-determining step in lipid peroxidation is the propagation step of the peroxyl radical, where generally two types of reactions occur: a) hydrogen-atom transfer from a donor to the peroxyl radical; b) peroxyl-radical addition to a carbon-carbon double bond. The hydrogen-atom transfer mechanism is well studied, but much less is known about the reactivities and products of peroxyl-radical addition reactions. The goal of this project is to elucidate factors governing the reactivity of peroxyl-radical addition to a double bond and the contribution of this mechanism to peroxidation of a number of biologically important lipids, including cholesterol biosynthetic precursors, fat-soluble vitamins, and polyunsaturated fatty acids. There are three research objectives: 1) Establish a "radical clock" to measure the rate constants of both hydrogen-atom transfer and peroxyl-radical addition; 2) Evaluate factors controlling the reactivities of peroxyl-radical addition to a double bond; 3) Elucidate the products and reaction mechanisms of free radical peroxidation of biologically important lipids.

在该项目中，由化学部化学结构、动力学与机理B项目资助，华盛顿大学药物化学系的徐立斌教授旨在开发化学工具来了解生物氧化的反应活性和反应机制。重要的脂质。了解脂质过氧化背后的基本化学具有广泛的影响，因为脂质过氧化在人类病理学中发挥着重要作用，例如衰老、动脉粥样硬化和退行性疾病。该项目处于物理有机化学和生物有机化学的交叉领域，利用现代分析化学技术，非常适合不同背景的科学家的培养。该研究小组还旨在通过向高中生和教师传播脂质过氧化知识，并吸引来自不同背景的本科生进入研究领域，将教育与研究计划结合起来。脂质过氧化的速率决定步骤是过氧自由基的传播步骤，其中通常发生两种类型的反应：a)氢原子从供体转移到过氧自由基； b) 碳-碳双键上的过氧自由基加成。氢原子转移机制已得到充分研究，但对过氧自由基加成反应的反应性和产物知之甚少。该项目的目标是阐明控制过氧自由基加成双键反应性的因素，以及该机制对许多生物学上重要的脂质过氧化的贡献，包括胆固醇生物合成前体、脂溶性维生素和多不饱和脂肪酸。研究目标有三个：1）建立“自由基时钟”来测量氢原子转移和过氧自由基加成的速率常数； 2) 评估控制过氧自由基加成双键反应性的因素； 3）阐明具有重要生物学意义的脂质自由基过氧化的产物和反应机制。