Guided Ion Beam and Computational Studies of Singlet Oxygen Reactions With Guanine Radical Cations in Nucleobases, Nucleosides, and Their Native and Mismatched Base Pairs

核碱基、核苷及其天然碱基对和错配碱基对中鸟嘌呤自由基阳离子的单线态氧反应的引导离子束和计算研究

• 批准号: 1856362
• 负责人: Jianbo Liu
• 金额: $ 42万
• 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: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1856362&HistoricalAwards=false
• 关键词: Guided; Ion; Beam; Computational; Studies

In this project funded by the Chemical Structure, Dynamics, and Mechanisms-A (CSDM-A) Program of the Chemistry Division, Professor Jianbo Liu and his students at the Queens College of the City University of New York (CUNY) is using combined experimental and theoretical approaches to study the chemical reaction of guanine radical cations with a reactive oxygen species called singlet oxygen. Guanine is one of the four nucleobases of RNA (ribonucleic acid) and DNA (deoxyribonucleic acid). It is normally a neutral molecule with all electrons paired, but when one electron is removed, it becomes what is called a radical cation. The radical form of a molecule is often more chemically reactive than its neutral form. Professor Liu and his research team are exploring the reaction of guanine radical cation and singlet oxygen, as this reaction provides insight into how living systems deal with damage to DNA and RNA, for example, from ultraviolet light exposure (sunburn). This research project may also advance photodynamic therapies for cancer treatments. This project is providing training for two doctoral and three Master's students each year. Professor Liu participates in Undergraduate Research Mentoring, Federal Work-Study and MARC-U*STAR Programs to recruit undergraduate research students. He also collaborates with CUNY Community College to integrate the community college faculty and students into his research program.The project uses electrospray ionization tandem mass spectrometry and guided ion beam to probe singlet oxygen reactions and C8-hydroxylation of the radical cations of guanine, guanosine, 8-oxoguanine and their base pairs, in the order of increasing structural complexity. Radical cations are produced by in-source dissociation of copper-guanine complexes and singlet oxygen is generated using a chemical source without other reactive oxygen contaminants. Different aspects of reaction mechanisms are examined, these include: collision energy dependence and exothermic/endothermic product channels. Also examined are the effects of base-pairing and mispairing, intra-base-pair proton transfer, non-Aufbau Singly Occupied Molecular Orbital (SOMO)-to-Highest Occupied Molecular Orbital (HOMO) level switching, and explicitly hydrogen-bonded water ligands. Experiments are complemented by electronic structure calculations, Rice?Ramsperger?Kassel?Marcus (RRKM) modeling and direct dynamics simulations. One research thrust is to explore and benchmark reliable theoretical methods for tackling the unique reaction systems of doublet-state radical cations with electronically excited singlet oxygen of mixed open- and closed-shell characters. The students involved in this research are gaining valuable experience not only in the science of nucleobase-singlet oxygen reaction dynamics, but in instrument design and construction, and computational modeling (e.g., reaction kinetics, dynamics and ion trajectory simulations). Many of the instruments developed for the research are also used in undergraduate laboratory courses. Queens College is a Minority Serving Institution, with 40% of students being the first in their families to attend college. The education and training aspects of this research project have direct implications for increasing diversity and broadening participation.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.

在该项目由化学结构，动力学和机制-A（CSDM-A）计划资助的项目中，纽约市皇后学院（CUNY）教授使用实验和理论方法来研究鸟嘌呤辐射式阳光阳离子的化学反应，该化学反应与称为单人牛的反应性牛的化学反应。鸟嘌呤是RNA（核糖核酸）和DNA（脱氧核糖核酸）的四个核碱基之一。 它通常是一个与所有电子配对的电子的中性分子，但是当去除一个电子时，它将变成所谓的自由基阳离子。 分子的自由基形式通常比中性形式具有化学反应性。 Liu教授和他的研究团队正在探索鸟嘌呤激进阳离子和单线氧的反应，因为这种反应提供了有关生命系统如何处理DNA和RNA损害的洞察力，例如，紫外线光暴露（Sunburn）。 该研究项目还可以推进癌症治疗的光动力疗法。 该项目每年为两个博士和三名硕士学生提供培训。 Liu教授参加了本科研究指导，联邦锻炼和MARC-U*明星计划，以招募本科生研究专业的学生。 他还与CUNY社区学院合作，将社区学院的教职员工和学生整合到他的研究计划中。该项目使用电喷雾电离串联质谱法和指导离子光束来探测单线氧反应和C8-羟基化鸟嘌呤，鸟氨酸，8-氧化剂及其底层的自由基阳离子，并提高了阶级，并提高了阶层的秩序。自由基阳离子是通过铜 - 瓜氨酸复合物的源源解离并产生的，而单线氧是使用没有其他活性氧污染物的化学源产生的。检查了反应机制的不同方面，其中包括：碰撞能量依赖性和放热/吸热产品通道。 还检查的是碱基配对和错误的基础质子质子转移的影响，非Aufbau单独占据的分子轨道（SOMO）对最高的分子轨道（HOMO）水平开关和明显的氢键键合的水配体的影响。通过电子结构计算，水稻Ramsperger？Kassel？Marcus（RRKM）建模和直接动力学模拟，实验补充了实验。一项研究的推力是探索和基准可靠的理论方法，以通过混合开放和封闭形状特征的电子激发的单线氧来应对双重激进阳离子的独特反应系统。参与这项研究的学生不仅在核碱基氧气反应动力学的科学中获得了宝贵的经验，而且还获得了仪器设计和构造以及计算建模（例如，反应动力学，动力学和离子轨迹模拟）。 为研究开发的许多工具也用于本科实验室课程。 皇后学院（Queens College）是少数派服务机构，有40％的学生是他们家庭中第一个上大学的学生。 该研究项目的教育和培训方面对增加多样性和扩大参与具有直接影响。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛的影响审查标准通过评估来支持的。

项目成果

Singlet O₂Oxidation of the Radical Cation versus the Dehydrogenated Neutral Radical of 9-Methylguanine in a Watson?Crick Base Pair. Consequences of Structural Context

沃森克里克碱基对中自由基阳离子与 9-甲基鸟嘌呤脱氢中性自由基的单线态 O₂氧化。

• DOI: 10.1021/acs.jpcb.2c03748
• 发表时间: 2022
• 期刊: The Journal of Physical Chemistry B
• 作者: Moe May Myat;Saito Toru;Tsai Midas;Liu Jianbo
• 通讯作者: Liu Jianbo

Effects of Intra‐Base Pair Proton Transfer on Dissociation and Singlet Oxygenation of 9‐Methyl‐8‐Oxoguanine−1‐Methyl‐Cytosine Base‐Pair Radical Cations

碱基对内质子转移对 9-甲基-8-氧鸟嘌呤-1-甲基-胞嘧啶碱基-自由基阳离子解离和单线态氧化的影响

• DOI: 10.1002/cphc.202300511
• 发表时间: 2023
• 期刊: ChemPhysChem
• 影响因子: 2.9
• 作者: Moe, May Myat;Tsai, Midas;Liu, Jianbo
• 通讯作者: Liu, Jianbo

Reaction mechanism and dynamics for C8-hydroxylation of 9-methylguanine radical cation by water molecules

水分子对9-甲基鸟嘌呤自由基阳离子C8-羟基化的反应机理和动力学

• DOI: 10.1039/d1cp03884b
• 发表时间: 2021
• 期刊: Physical Chemistry Chemical Physics
• 影响因子: 3.3
• 作者: Zhou, Wenjing;Liu, Jianbo
• 通讯作者: Liu, Jianbo

Collision-induced dissociation of homodimeric and heterodimeric radical cations of 9-methylguanine and 9-methyl-8-oxoguanine: correlation between intra-base pair proton transfer originating from the N1–H at a Watson–Crick edge and non-statistical dissocia

9-甲基鸟嘌呤和 9-甲基-8-氧代鸟嘌呤的同二聚体和异二聚体自由基阳离子的碰撞诱导解离：源自 Watson–Crick 边缘 N1–H 的碱基对内质子转移与非统计解离之间的相关性

• DOI: 10.1039/d2cp00312k
• 发表时间: 2022
• 期刊: Physical Chemistry Chemical Physics
• 影响因子: 3.3
• 作者: Moe, May Myat;Benny, Jonathan;Liu, Jianbo
• 通讯作者: Liu, Jianbo