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

有了这个奖项，化学系的化学结构，动力学和机制（CSDM-A）计划资助纽约市立大学皇后学院的刘建波教授研究激发态氧与DNA鸟嘌呤碱基的反应。氧对鸟嘌呤的损伤是一个关键的化学步骤，其生物学后果从光裂解、诱变和致癌到细胞致死。具体来说，氧化产物涉及神经系统疾病如阿尔茨海默氏症和帕金森氏症的基本化学。本计画将探讨鸟嘌呤在不同环境中的氧化机制，并将决定鸟嘌呤氧化修饰对碱基配对及DNA-蛋白质交联的影响。该项目也有很强的教育成分，使本科生和研究生进入研究实验室。 预计这将有助于扩大参与，因为皇后学院为大量（40%）第一代大学生提供服务;其中约一半是少数民族背景。该项目使用电喷雾质谱（ESI-MS）和引导离子束散射探测鸟嘌呤及其衍生物在气相中的单线态氧氧化。反应截面测量质子化/去质子化鸟嘌呤离子和鸟嘌呤离子与水的集群作为碰撞能量的函数。气相实验后，相同的系统进行了研究，在水溶液中使用在线光谱和ESI-MS/MS。其他主要的实验推力是研究鸟嘌呤氧化的后果，其碱基配对与胞嘧啶和与赖氨酸的交联反应。这些实验的补充，电子结构计算的反应坐标，RRKM模拟复杂介导的途径，动力学行为的轨迹模拟。这些研究旨在探索和阐明这些单线态氧反应的机制。

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.