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

化学系化学结构、动力学和机理（CSDM-A）项目将资助纽约市立大学皇后学院刘建波教授研究一种激发态氧与DNA鸟嘌呤碱基的反应。氧损伤鸟嘌呤是一个关键的化学步骤，具有从光裂解、诱变、致癌到细胞致死等一系列生物学后果。具体来说，氧化产物与阿尔茨海默病和帕金森病等神经系统疾病的基本化学反应有关。该项目将研究不同环境下的氧化机制，并将确定鸟嘌呤氧化修饰对碱基配对和dna -蛋白质交联的影响。该项目还具有很强的教育成分，将本科生和研究生带入研究实验室。由于皇后学院为大量（40%）的第一代大学生提供服务，预计这将有助于扩大参与；其中大约一半是少数民族背景。该项目使用电喷雾质谱法（ESI-MS）和引导离子束散射来探测鸟嘌呤及其衍生物在气相中的单线态氧氧化。反应截面作为质子化/去质子化鸟嘌呤离子和鸟嘌呤离子与水聚集的碰撞能量的函数来测量。在气相实验之后，同样的系统将在水溶液中使用在线光谱和ESI-MS/MS进行研究。另一个主要的实验重点是研究鸟嘌呤氧化对其与胞嘧啶的碱基配对以及与赖氨酸的交联反应的影响。这些实验由反应坐标的电子结构计算、复杂介导途径的RRKM建模和动力学行为的轨迹模拟来补充。这些研究旨在探索和阐明这些单线态氧反应的机理。

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.