Moe May Myat, Tsai Midas, Liu Jianbo
Department of Chemistry and Biochemistry, Queens College of the City University of New York, 65-30 Kissena Blvd., Queens, NY 11367, USA.
Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, 365 5th Ave., New York, NY 10016, USA.
Chemphyschem. 2023 Dec 1;24(23):e202300511. doi: 10.1002/cphc.202300511. Epub 2023 Oct 6.
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 ( O ) 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 - H ]⋅ ⋅ [1MC+H ] and subsequent non-statistical base-pair separation. We then measured the reaction of [9MOG ⋅ 1MC]⋅ with O , revealing the two most probable pathways, C5-O addition and H -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 and O (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 toward O as [9MOG - H]⋅>9MOG⋅ >[9MOG - H ]⋅ ⋅ [1MC+H ] ≥9MOG⋅ ⋅ 1MC.
8-氧代鸟苷是最常见的氧化产生的碱基损伤，在双链DNA中与互补的胞嘧啶配对。8-氧代鸟苷-胞嘧啶损伤若未被识别和去除，不仅会导致G到T的颠换突变，还会使碱基对更容易受到电离辐射和单线态氧（O）的损伤。在此，使用质谱联用电喷雾电离技术研究了由9-甲基-8-氧代鸟嘌呤自由基阳离子（9MOG⋅ ）和1-甲基胞嘧啶（1MC）组成的原型沃森-克里克碱基对[9MOG ⋅ 1MC]⋅ 的反应动力学。我们首先检测到与氙气碰撞时碱基对的解离，这为了解9MOG⋅ ⋅ 1MC [9MOG - H ]⋅ ⋅ [1MC+H ]的碱基对内质子转移及随后的非统计性碱基对分离提供了线索。然后我们测量了[9MOG ⋅ 1MC]⋅ 与O的反应，揭示了两条最可能的途径，即9MOG处的C5 - O加成和H - 夺取。反应与9MOG自由基的两种形式、碱基对结构以及开壳层自由基与O（具有混合单重态/三重态特征）之间的多种构型相互纠缠。通过利用近似自旋投影密度泛函理论、耦合簇理论和多参考电子结构建模，这些纠缠得以解开。这项工作描绘了碱基对结构背景效应，并确定了对O的相对反应活性为[9MOG - H]⋅>9MOG⋅ >[9MOG - H ]⋅ ⋅ [1MC+H ] ≥9MOG⋅ ⋅ 1MC。
