Chemical Reactivity and Redox Behavior of Heme-HNOx Derivatives

在这个由化学系化学结构、动力学和机制B计划资助的项目中，俄克拉荷马大学化学和生物化学系的George Richter-Addo教授和南伊利诺伊大学爱德华兹维尔大学化学系的Michael Shaw教授将研究铁在各种与环境和人类健康相关的氮氧化物新陈代谢中的作用，如温室气体一氧化二氮和血压控制剂一氧化氮。许多酶含有铁，而金属在决定氮氧化物物种如何化学转化方面发挥着重要作用。然而，蛋白质包裹的铁在指导氮氧化物代谢机制中的确切作用仍然相对未知。这个合作项目将利用合成、电化学和计算化学的组合作为指导，沿着生物反应途径分离和表征不稳定的铁氮氧化物中间体，并允许更好地了解铁在实现生物相关氮氧化物相互转化中的化学作用。合作团队将博士环境和以本科生为主的环境相结合，为不同的学生群体提供高水平的研究培训。教育和推广活动将包括将现代电化学和计算化学纳入本科新生化学课程，积极参与市中心有可能失败的高中生的暑期计划，以及在适合残疾人的多人环境中制作在线授课教育视频。氮氧化物(NOx)是全球氮循环的关键组成部分。气态一氧化二氮是一种温室气体，由真菌中使用单铁血红素蛋白活性部位的血红素蛋白和使用血红素/非血红素二铁活性部位的细菌中的血红素蛋白产生。无机-NOx化合物向与农业和生物学有关的有机-NOx物种的相互转化也是由一些血红素蛋白介导的。在这个项目中，将研究导致血红素介导的一氧化氮(NO)、一氧化二氮(N2O)、氮氧基(HNO)和(烷基)羟胺(RNHOH)相互转化的因素。研究小组将利用合成、光谱电化学和计算化学相结合的方法来确定分离和表征不稳定中间体的实验条件，以帮助阐明(I)在NO偶合形成温室气体一氧化二氮的过程中涉及的关键N-N键形成步骤，以及(Ii)无机-NOx向有机-NOx转化中的N-C键形成步骤的机制。将特别强调非金属和含金属的Lewis酸在激活N-N和N-C键形成反应中结合的NO基团中的作用。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

In this project, funded by the Chemical Structure, Dynamics, and Mechanism B Program of the Division of Chemistry, Professor George Richter-Addo of the Department of Chemistry and Biochemistry at the University of Oklahoma and Professor Michael Shaw, of the Department of Chemistry at Southern Illinois University Edwardsville will study the role of iron in the metabolism of various nitrogen oxides of relevance to the environment and human health, such as the greenhouse gas nitrous oxide and the blood pressure control agent nitric oxide. Many enzymes contain iron, and the metal plays a major role in determining how nitrogen oxides species are chemically transformed. However, the exact role of protein-encapsulated iron in directing the mechanisms of nitrogen oxides metabolism remains relatively unexplored. This collaborative project will utilize a combination of synthesis, electrochemistry, and computational chemistry as guides for the isolation and characterization of unstable iron nitrogen oxide intermediates along biological reaction pathways, and to allow for a better understanding of the chemical role of iron in enabling the interconversions of biologically relevant nitrogen oxides. The collaborative team combines a Ph.D. environment and a primarily undergraduate environment to provide high-level research training to a diverse group of students. Educational and outreach activities will involve the incorporation of modern electrochemistry and computational chemistry in undergraduate freshman chemistry courses, active participation in an summer program for inner city high school kids at risk for failure in academic programs, and production of online lecture educational videos in a multiplayer environment suitable for individuals with disabilities.Nitrogen oxides (NOx) are key components of the global nitrogen cycle. Gaseous nitrous oxide is a greenhouse gas that is generated by heme proteins in fungi using a mono-Fe heme protein active site, and in bacteria using a heme/non-heme di-Fe active site. The interconversion of inorganic-NOx compounds to organo-NOx species of relevance to agriculture and biology is also mediated by some heme proteins. In this project, the factors that lead to heme-mediated interconversions of nitric oxide (NO), nitrous oxide, nitroxyl (HNO), and (alkyl)hydroxylamines (RNHOH) will be studied. The research team will utilize a combination of synthesis, spectro-electrochemistry, and computational chemistry to determine experimental conditions that will allow for the isolation and characterization of unstable intermediates, to help elucidate the mechanisms of (i) the critical N–N bond forming step involved in NO coupling to form the greenhouse gas nitrous oxide, and (ii) the N–C bond forming steps in inorganic-NOx to organo-NOx conversions. Particular emphasis will be placed on the role of non-metal and metal-containing Lewis acids in activating bound-NO groups towards such N–N and N–C bond-forming reactions. Extensions to other biologically relevant NOx reactions will also be made.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.