Effects of Intra‐Base Pair Proton Transfer on Dissociation and Singlet Oxygenation of 9‐Methyl‐8‐Oxoguanine−1‐Methyl‐Cytosine Base‐Pair Radical Cations
Effects of Intra‐Base Pair Proton Transfer on Dissociation and Singlet Oxygenation of 9‐Methyl‐8‐Oxoguanine−1‐Methyl‐Cytosine Base‐Pair Radical Cations
复制标题
碱基对内质子转移对 9-甲基-8-氧鸟嘌呤-1-甲基-胞嘧啶碱基-自由基阳离子解离和单线态氧化的影响
DOI：
10.1002/cphc.202300511
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发表时间：
2023
期刊：
影响因子：
2.9
通讯作者：
Liu, Jianbo
中科院分区：
文献类型：
--
作者：
Moe, May Myat;Tsai, Midas;Liu, Jianbo
8-氧代鸟苷是最常见的氧化产生的碱基损伤，并与双链 DNA 内的互补胞苷配对。 8-氧代鸟苷-胞苷损伤如果不被识别和去除，不仅会导致 G-to-T 颠换突变，而且会使碱基对更容易受到电离辐射和单线态氧 (1O2) 损伤。在此，使用质谱法结合电喷雾电离检查了由 9-甲基-8-氧代鸟嘌呤自由基阳离子 (9MOG⋅+) 和 1-甲基半胱氨酸 (1MC) 组成的原型 Watson-Crick 碱基对 [9MOG ⋅ 1MC]⋅+ 的反应动力学。我们首先检测到与 Xe 气体碰撞时的碱基对解离，这为了解 9MOG⋅+⋅ 1MC [9MOG − HN1]⋅ ⋅ [1MC+HN3′]+ 的碱基对内质子转移以及随后的非统计碱基对分离提供了见解。然后我们测量了 [9MOG ⋅ 1MC]⋅+ 与 1O2 的反应，揭示了两个最可能的途径，即 9MOG 时的 C5-O2 加成和 HN7-抽象。反应与两种形式的 9MOG 自由基和碱基对结构以及开壳自由基和 1O2（具有混合单线态/三线态特征）之间的多重构型纠缠在一起。通过利用近似自旋投影密度泛函理论、耦合团簇理论和多参考电子结构建模来解开这些问题。该工作描述了碱基对结构背景效应，并确定了对 1O2 的相对反应性为 [9MOG − H]⋅>9MOG⋅+>[9MOG − HN1]⋅ ⋅ [1MC+HN3′]+≥9MOG⋅+⋅ 1MC。
8‐Oxoguanosine is the most common oxidatively generated base damage and pairs with complementary cytidine within duplex DNA. The 8‐oxoguanosine−cytidine lesion, if not recognized and removed, not only leads to G‐to‐T transversion mutations but renders the base pair being more vulnerable to the ionizing radiation and singlet oxygen (1O2) damage. Herein, reaction dynamics of a prototype Watson−Crick base pair [9MOG ⋅ 1MC]⋅+, consisting of 9‐methyl‐8‐oxoguanine radical cation (9MOG⋅+) and 1‐methylcystosine (1MC), was examined using mass spectrometry coupled with electrospray ionization. We first detected base‐pair dissociation in collisions with the Xe gas, which provided insight into intra‐base pair proton transfer of 9MOG⋅+⋅ 1MC [9MOG − HN1]⋅ ⋅ [1MC+HN3′]+and subsequent non‐statistical base‐pair separation. We then measured the reaction of [9MOG ⋅ 1MC]⋅+with1O2, revealing the two most probable pathways, C5‐O2addition and HN7‐abstraction at 9MOG. Reactions were entangled with the two forms of 9MOG radicals and base‐pair structures as well as multi‐configurations between open‐shell radicals and1O2(that has a mixed singlet/triplet character). These were disentangled by utilizing approximately spin‐projected density functional theory, coupled‐cluster theory and multi‐referential electronic structure modeling. The work delineated base‐pair structural context effects and determined relative reactivity toward1O2as [9MOG − H]⋅>9MOG⋅+>[9MOG − HN1]⋅ ⋅ [1MC+HN3′]+≥9MOG⋅+⋅ 1MC.