Study on singlet oxygen-mediated oxidation mechanism, dynamics and consequences of the guanine base of DNA using gas- and solution-phase techniques and dynamics simulations

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With this award, the Chemical Structure, Dynamics and Mechanisms (CSDM-A) Program of the Division of Chemistry is funding Professor Jianbo Liu of CUNY Queens College to study the reaction of an excited form of oxygen with the guanine base of DNA. Oxygen damage to guanine is a key chemical step with biological consequences that range from photocleavage, mutagenesis and carcinogenesis to cellular lethality. Specifically, the oxidation products are involved in the basic chemistry of neurological disorders such as Alzheimer's and Parkinson's diseases. This project will investigate the oxidation mechanisms in different environments, and will determine the consequences of guanine oxidative modifications on base pairing and DNA-protein cross-links. The project also has a strong educational component, bringing undergraduate and graduate students into the research laboratory. This is expected to help broaden participation as Queens College serves a large number (40%) of first generation college students; about half of these are of minority background. The project uses electrospray mass spectrometry (ESI-MS) and guided-ion-beam scattering to probe the singlet oxygen oxidation of guanine and its derivatives in the gas phase. Reaction cross sections are measured as a function of collision energy for protonated/deprotonated guanine ions and for guanine ions clustering with water. Following the gas-phase experiments, the same systems are to be investigated in aqueous solutions using on-line spectroscopy and ESI-MS/MS. The other major experimental thrust is to study the consequences of guanine oxidation on its base pairing with cytosine and on cross-linking reactions with lysine. These experiments are complemented by electronic structure calculations of reaction coordinates, RRKM modeling of complex mediated pathways, and trajectory simulations of dynamics behaviors. These studies are directed at exploring and elucidating the mechanism of these singlet oxygen reactions.