DNA/RNA photohydrates represent a class of well-known biomolecular lesions formed by the absorption of near- to mid-UV light. They are formed via a photoinduced nucleophilic hydrolysis reaction in which water is split (via nucleobase sensitisation) into H + OH radicals. These nascent radicals can then add across C5C6, saturating the preexisting double bond. If unrepaired, such lesions can lead to mutagenic carcinogenesis, which is responsible for several forms of cancer. Using high-level electronic structure theory (CASPT2), we map the key excited-state reaction paths associated with the reactivity of DNA (guanine and thymine) and RNA (uracil) nucleobases with water. At the outset, we consider the intrinsic reactivity in the isolated gas phase – in which the water (cluster) + chromophore complex is free from environmental perturbations. We then extrapolate the thymine nucleobase to the bulk DNA environment in aqueous solution in order to ascertain the relative importance of hydrate formation in a more complex biological environment. In this latter study we use high-level mixed quantum/classical (QM/MM: CASPT2/AMBER) methods.

中文翻译：

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关于气相和本体溶液中光诱导的DNA和RNA核碱基损伤的机理的见解

DNA / RNA光水合物代表一类由吸收近中紫外光形成的众所周知的生物分子损伤。它们是通过光诱导的亲核水解反应形成的，其中水被分裂（通过核碱基敏化）成H + OH自由基。这些新生的自由基可以在C5上加成C6，使先前存在的双键饱和。如果未修复，此类病变会导致致癌性致癌，这是多种癌症的原因。使用高级电子结构理论（CASPT2），我们绘制了与DNA（鸟嘌呤和胸腺嘧啶）和RNA（尿嘧啶）核碱基与水的反应性相关的关键激发态反应路径。首先，我们考虑了孤立气相中的固有反应性，其中水（簇）+生色团络合物不受环境干扰。然后，我们将胸腺嘧啶核苷外推到水溶液中的大量DNA环境中，以确定在更复杂的生物环境中水合物形成的相对重要性。在后面的研究中，我们使用高级混合量子/经典（QM / MM：CASPT2 / AMBER）方法。