Nitrosation and Nitration Reactions of the Radical Cations of Guanine, 8-Oxoguanine and their Derivatives by NOx: Radical-radical Interactions at Multiple Electron Configurations

鸟嘌呤、8-氧代鸟嘌呤及其衍生物的自由基阳离子与 NOx 的亚硝化和硝化反应：多电子构型下的自由基-自由基相互作用

• 批准号: 2350109
• 负责人: Jianbo Liu
• 金额: $ 50.6万
• 依托单位: CUNY Queens College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2350109&HistoricalAwards=false
• 关键词: Nitrosation; Nitration; Reactions; Radical; Cations

With support from the Chemical Structure, Dynamics, and Mechanisms A (CSDM-A) program in the Division of Chemistry, Professor Jianbo Liu of Queens College is investigating the reactions of the radical cations of guanine and its oxidized derivative 8-oxoguanine with nitric oxide (NO) and nitrogen dioxide (NO2) using electrospray ionization and mass spectrometry. Guanine has the lowest oxidation and ionization potential among DNA nucleobases, leading to the preferential formation of the radical cations of guanine and 8-oxoguanine upon the oxidation and ionization of DNA. Reactions of these radical cations are difficult to study in solution due to their rapid deprotonation and the inability to separate, detect, and characterize products. Professor Liu and his students will study the reactions of these radical cations with NO and NO2 in a rarefied gas-phase environment where individual products can be measured. These studies are expected to provide a better understanding of DNA damage upon oxidative, nitrosative, and nitrative stress. The students working on this project will gain experience in reaction dynamics, instrumentation development, and computational modeling. Queens College is a Minority Serving Institution, with 40% of students from traditionally underserved groups. This project have direct implications for diversity and broadening participation, including collaboration with LaGuardia Community College to transfer qualified students from an associate degree to the Chemistry B.S. program. Many of the instruments developed for research will also used in undergraduate laboratory courses.The project will utilize electrospray ionization and guided-ion beam tandem mass spectrometry to conduct ion-molecule reactions wherein the radical cations of guanine and 8-oxoguanine are produced by electron-transfer induced-dissociation of Cu(II)-nucleobase complexes. Reactions of mass-selected radical cations with NO and NO2 will be carried out under gas-phase single-collision conditions provided in the guided-ion beam scattering experiment where structures and cross sections of individual product ions will be measured as a function of collision energy. Experiments will be complemented by electronic structure calculations, dynamics simulations, and kinetic analysis. The in-house, synergetic experiments and computations should allow for interpretation of various aspects of reaction mechanism and non-adiabatic kinetics. A major thrust of this research is to benchmark experiment and theory for tackling multireferential characters and non-adiabatic transitions in doublet-doublet electronic-state reactions.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.

在化学系化学结构、动力学和机理A (CSDM-A)项目的支持下，皇后学院的Jianbo Liu教授正在研究鸟嘌呤及其氧化衍生物8-氧代鸟嘌呤的自由基阳离子与一氧化氮的反应(NO) 和二氧化氮 (NO2) 使用电喷雾电离和质谱法。鸟嘌呤在DNA核碱基中具有最低的氧化和电离电势，导致DNA氧化和电离时优先形成鸟嘌呤和8-氧代鸟嘌呤的自由基阳离子。由于这些自由基阳离子的去质子化速度快且无法分离、检测和表征产物，因此很难在溶液中研究这些自由基阳离子的反应。刘教授和他的学生将研究这些自由基阳离子与NO和NO2在稀薄气相环境中的反应，在该环境中可以测量单个产物。这些研究有望更好地了解氧化、亚硝化和硝化应激造成的 DNA 损伤。从事该项目的学生将获得反应动力学、仪器开发和计算建模方面的经验。 皇后学院是一所少数族裔服务机构，40% 的学生来自传统上服务不足的群体。该项目对多样性和扩大参与具有直接影响，包括与拉瓜迪亚社区学院合作，将合格的学生从副学士学位转学到化学学士学位。程序。许多为研究而开发的仪器也将在本科生实验室课程中使用。该项目将利用电喷雾电离和引导离子束串联质谱法进行离子-分子反应，其中鸟嘌呤和8-氧代鸟嘌呤的自由基阳离子是通过电子-分子反应产生的。 Cu(II)-核碱基复合物的转移诱导解离。质量选择的自由基阳离子与 NO 和 NO2 的反应将在引导离子束散射实验中提供的气相单碰撞条件下进行，其中将测量各个产物离子的结构和横截面作为碰撞能量的函数。实验将辅以电子结构计算、动力学模拟和动力学分析。内部协同实验和计算应该能够解释反应机制和非绝热动力学的各个方面。这项研究的一个主要目标是为解决双重态电子态反应中的多指特征和非绝热转变提供基准实验和理论。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值进行评估，被认为值得支持以及更广泛的影响审查标准。