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

纽约皇后学院的刘建波教授和他的学生在化学系化学结构、动力学和机理-A（CSDM-A）项目的资助下，采用实验和理论相结合的方法，研究鸟嘌呤自由基阳离子与一种称为单线态氧的活性氧的化学反应。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。 它通常是一个中性分子，所有电子都成对，但当一个电子被移除时，它就变成了所谓的自由基阳离子。 分子的自由基形式通常比其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处理DNA和RNA的损伤，例如，紫外线照射（晒伤）。 该研究项目还可能推进光动力疗法用于癌症治疗。 该项目每年为两名博士生和三名硕士生提供培训。 刘教授参与本科生研究指导、联邦勤工俭学和MARC-U* 星星计划，招收本科生研究生。 他还与纽约城市大学社区学院合作，将社区学院的教师和学生融入他的研究计划。该项目使用电喷雾串联质谱和引导离子束探测单重态氧反应和鸟嘌呤，鸟苷，8-氧代鸟嘌呤及其碱基对的自由基阳离子的C8-羟基化，按照结构复杂性增加的顺序。自由基阳离子通过铜-鸟嘌呤复合物的源内解离产生，并且使用没有其他活性氧污染物的化学源产生单线态氧。反应机理的不同方面进行了研究，这些包括：碰撞能量依赖性和放热/吸热产物通道。 还研究了碱基配对和错配、碱基对内质子转移、非Aufbau单占据分子轨道（SOMO）至最高占据分子轨道（HOMO）能级切换以及显式氢键水配体的影响。实验的补充电子结构计算，赖斯？Ramsperger？卡塞尔？Marcus（RRKM）建模和直接动力学仿真。一个研究重点是探索和基准可靠的理论方法，以解决独特的反应系统的双态自由基阳离子与电子激发单线态氧的混合开壳层和闭壳层字符。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）。 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民族服务机构，40%的学生是家庭中第一个上大学的。 该研究项目的教育和培训方面对增加多样性和扩大参与有直接影响。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 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.