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

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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.