Mechanisms of direct and indirect DNA damages induced by stimuli from environment such as radiation and active oxygen

为了研究辐射对DNA碱基直接损伤的机制，我们研究了模型分子2-氨基-3甲基吡啶在碳和氮k边的断裂。我们发现，在氮的k壳电离能处，发生了一个特定的反应，在这个反应中，氮原子周围产生了大量破碎的碎片离子。以2-、3-和4-吡啶为样品的实验支持了该体系的破碎机理。利用红外光谱结合量子化学计算，研究了低温氩气基质中2-氨基吡啶及其衍生物的光致互变异构现象。在340 >λ（大于等于300 nm）的紫外照射下，氨基互变异构体转变为亚氨基互变异构体，而在较长波长（370 >λ（大于等于340 nm））的紫外照射下，氨基互变异构体发生逆反应。还鉴定了T_1态氨基互变异构体的光诱导瞬态红外带。从不同的理论层面对8-氧鸟嘌呤（80G）和鸟嘌呤(G)互变异构体的相对稳定性进行了全面研究。我们发现，在任何理论水平下，80G中C6位置的烯醇形态的居布率都高于G。利用红外光谱和量子化学计算系统地研究了溶剂对2-吡啶酮（2PY）酮-烯醇互变异构的影响。在低温氩气基体中，2PY的酮类和烯类互变异构体共存，而在室温下，2PY的酮类互变异构体主要存在于稀四氯化碳溶液中。烯醇互变异构体随着温度的升高而轻微出现。2PY的互变异构很大程度上取决于环境。量子化学计算预测的2PY酮互变异构体的稳定性与实验结果定性一致。

To investigate the mechanisms of direct damage to DNA bases induced by radiation, we studied the fragmentation of a model molecule, 2-amino-3methylpyridine, at the carbon and nitrogen K-edges. We found that at the nitrogen K-shell ionization energies a specific reaction occurs in which fragment ions with the breakup around the nitrogen atoms are significantly produced. The proposed fragmentation mechanism for this system is supported by the experiments with 2-, 3-, and 4-picolines as samples.The photo-induced tautomerism of 2-aminopyridine and its derivatives was investigated in a low temperature argon matrix by infrared spectroscopy combined with quantum chemical calculations. The amino tautomer changes to the imino tautomer by UV irradiation (340 >λ【greater than or equal】 300 nm), and the reverse reaction occurs by that with a longer wavelength (370 >λ【greater than or equal】340 nm). Photo-induced transient IR bands assigned to the amino tautomer in the T_1 state were also identified.The relative stabilities of tautomers of 8-oxoguanine (80G) and guanine (G) were investigated comprehensively at various levels of theory. We found that the population of the enol form at C6 position in 80G is higher than that in G at any level of theory which we used. This may partly account for the high mutagenicity of 80GThe solvent-effects on the keto-enol tautomerism of 2-pyridone (2PY) were systematically investigated by infrared spectroscopy and quantum chemical calculations. In a low temperature argon matrix, the keto and enol tautomers of 2PY coexist, while the keto tautomer of 2PY is predominantly observed in the dilute carbon tetrachloride solution at room temperature. The enol tautomer slightly appears as temperature goes up. The tautomerism of 2PY strongly depends on the environment. The stability of the keto tautomer of 2PY predicted by quantum chemical calculation is qualitatively in good agreements with the experimental result.