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.

在这个由化学系化学结构、动力学和机理-A（CSDM-A）项目资助的项目中，纽约市立大学（CUNY）皇后学院的刘剑波教授和他的学生采用了组合实验以及研究鸟嘌呤自由基阳离子与称为单线态氧的活性氧的化学反应的理论方法。鸟嘌呤是RNA（核糖核酸）和DNA（脱氧核糖核酸）的四种核碱基之一。 它通常是一种所有电子配对的中性分子，但当一个电子被移除时，它就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更具化学反应性。 刘教授和他的研究团队正在探索鸟嘌呤自由基阳离子和单线态氧的反应，因为这种反应可以深入了解生命系统如何应对 DNA 和 RNA 的损伤，例如紫外线照射（晒伤）造成的损伤。 该研究项目还可能推进癌症治疗的光动力疗法。 该项目每年培养两名博士生和三名硕士生。 刘教授参与本科生研究指导、联邦勤工俭学和 MARC-U*STAR 项目招收本科生。 他还与纽约市立社区学院合作，将社区学院的教职员工和学生纳入他的研究计划。该项目使用电喷雾电离串联质谱和引导离子束来探测鸟嘌呤、鸟苷、 8-氧代鸟嘌呤及其碱基对，按照结构复杂性递增的顺序。自由基阳离子是通过铜-鸟嘌呤络合物的源内解离产生的，并且使用化学源产生单线态氧，不含其他活性氧污染物。研究了反应机制的不同方面，包括：碰撞能量依赖性和放热/吸热产物通道。 还检查了碱基配对和错配、碱基对内质子转移、非 Aufbau 单占据分子轨道 (SOMO) 到最高占据分子轨道 (HOMO) 能级转换以及明确氢键水配体的影响。实验还辅以电子结构计算、Rice?Ramsperger?Kassel?Marcus (RRKM) 建模和直接动力学模拟。研究重点之一是探索和基准测试可靠的理论方法，以解决双态自由基阳离子与混合开壳层和闭壳层特征的电子激发单线态氧的独特反应体系。参与这项研究的学生不仅在核碱基-单线态氧反应动力学科学方面获得了宝贵的经验，而且在仪器设计和建造以及计算建模（例如反应动力学、动力学和离子轨迹模拟）方面也获得了宝贵的经验。 许多为研究开发的仪器也用于本科实验室课程。 皇后学院是一所少数族裔服务机构，40% 的学生是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 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Experimental and theoretical assessment of protonated Hoogsteen 9-methylguanine–1-methylcytosine base-pair dissociation: kinetics within a statistical reaction framework

质子化 Hoogsteen 9-甲基鸟嘌呤-1-甲基胞嘧啶碱基对解离的实验和理论评估：统计反应框架内的动力学

• DOI: 10.1039/d0cp06682f
• 发表时间: 2021-04
• 期刊: Physical Chemistry Chemical Physics
• 影响因子: 3.3
• 作者: Moe, May Myat;Benny, Jonathan;Sun, Yan;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: 2023-10
• 期刊: ChemPhysChem
• 影响因子: 2.9
• 作者: Moe, May Myat;Tsai, Midas;Liu, Jianbo
• 通讯作者: Liu, Jianbo

Mass spectrometry and computational study of collision-induced dissociation of 9-methylguanine–1-methylcytosine base-pair radical cation: intra-base-pair proton transfer and hydrogen transfer, non-statistical dissociation, and reaction with a water ligand

9-甲基鸟嘌呤-1-甲基胞嘧啶碱基对自由基阳离子碰撞诱导解离的质谱分析和计算研究：碱基对内质子转移和氢转移、非统计解离以及与水配体的反应

• DOI: 10.1039/d0cp01788d
• 发表时间: 2020-07
• 期刊: Physical Chemistry Chemical Physics
• 影响因子: 3.3
• 作者: Sun, Yan;Moe, May Myat;Liu, Jianbo
• 通讯作者: Liu, Jianbo

Singlet Oxygen Oxidation of the Radical Cations of 8‐Oxo‐2′‐deoxyguanosine and Its 9‐Methyl Analogue: Dynamics, Potential Energy Surface, and Products Mediated by C5‐O 2 ‐Addition

8-氧代-2-2-脱氧鸟苷及其 9-甲基类似物的自由基阳离子的单线态氧氧化：动力学、势能面和由 C5-O 2 -加成介导的产物

• DOI: 10.1002/cplu.202100238
• 发表时间: 2021-07
• 期刊: ChemPlusChem
• 影响因子: 3.4
• 作者: Moe, May Myat;Tsai, Midas;Liu, Jianbo
• 通讯作者: Liu, Jianbo

Probing the Transition State-to-Intermediate Continuum: Mechanistic Distinction between a Dry versus Wet Perepoxide in the Singlet Oxygen “Ene” Reaction at the Air–Water Interface

探索过渡态到中间连续体：空气-水界面单线态氧-烯-反应中干过氧化物与湿过氧化物之间的机理区别

• DOI: 10.1021/acs.langmuir.2c00279
• 发表时间: 2022-05
• 期刊: Langmuir
• 影响因子: 3.9
• 作者: Malek, Belaid;Lu, Wenchao;Mohapatra, Prabhu Prasad;Walalawela, Niluksha;Jabeen, Shakeela;Liu, Jianbo;Greer, Alexander
• 通讯作者: Greer, Alexander