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，俄克拉荷马州大学化学和生物化学系的乔治里希特-阿多教授和南伊利诺伊大学爱德华兹维尔分校化学系的迈克尔·肖教授将研究铁在与环境和人类健康有关的各种氮氧化物代谢中的作用，例如温室气体一氧化二氮和血压控制剂一氧化氮。许多酶都含有铁，而铁在决定氮氧化物如何化学转化方面起着重要作用。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被探索。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南的分离和表征不稳定的铁氮氧化物中间体沿着生物反应途径，并允许更好地了解铁的化学作用，使生物相关的氮氧化物的相互转化。该合作团队结合了一个博士学位。环境和主要是本科生的环境，提供高水平的研究培训，以不同的学生群体。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的化学课程，积极参与针对有学术课程失败风险的内城高中学生的暑期课程，以及在适合残疾人的多人环境中制作在线讲座教育视频。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，由血红素蛋白在真菌中使用单铁血红素蛋白活性位点产生，在细菌中使用血红素/非血红素二铁活性位点产生。与农业和生物学相关的无机氮氧化物化合物与有机氮氧化物物种的相互转化也由一些血红素蛋白介导。 在这个项目中，导致血红素介导的一氧化氮（NO），一氧化二氮，硝酰基（HNO）和（烷基）羟胺（RNHOH）的相互转化的因素将被研究。该研究小组将利用合成，光谱电化学和计算化学的组合来确定实验条件，这些条件将允许分离和表征不稳定的中间体，以帮助阐明以下机制：（i）NO偶联形成温室气体一氧化二氮的关键N-N键形成步骤，和（ii）无机-NOx到有机-NOx转化中的N-C键形成步骤。 特别强调的是非金属和含金属的刘易斯酸在活化结合NO基团对这样的N-N和N-C键形成反应的作用。该奖项反映了NSF的法定使命，并被认为值得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来支持。

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.