Department of Chemistry and Biochemistry, Queens College of the City University of New York, 65-30 Kissena Blvd., Queens, New York 11367, United States.
Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, 365 5th Avenue, New York, New York 10016, United States.
J Phys Chem B. 2022 Jul 28;126(29):5458-5472. doi: 10.1021/acs.jpcb.2c03748. Epub 2022 Jul 18.
In DNA, guanine is the most susceptible to oxidative damage by exogenously and endogenously produced electronically excited singlet oxygen (O). The reaction mechanism and the product outcome strongly depend on the nucleobase ionization state and structural context. Previously, exposure of a monomeric 9-methylguanine radical cation (9MG, a model guanosine compound) to O was found to result in the formation of an 8-peroxide as the initial product. The present work explores the O oxidation of 9MG and its dehydrogenated neutral form [9MG - H] within a Watson-Crick base pair consisting of one-electron-oxidized 9-methylguanine-1-methylcytosine [9MG·1MC]. Emphasis is placed on entangling the base pair structural context and intra-base pair proton transfer with and consequences thereof on the singlet oxygenation of guanine radical species. Electrospray ionization coupled with guided-ion beam tandem mass spectrometry was used to study the formation and reaction of guanine radical species in the gas phase. The O oxidation of both 9MG and [9MG - H] is exothermic and proceeds barrierlessly either in an isolated monomer or within a base pair. Single- and multi-referential theories were tested for treating spin contaminations and multi-configurations occurring in radical-O interactions, and reaction potential energy surfaces were mapped out to support experimental findings. The work provides a comprehensive profile for the singlet oxygenation of guanine radicals in different charge states and in the absence and the presence of base pairing. All results point to an 8-peroxide as the major oxidation product in the experiment, and the oxidation becomes slightly more favorable in a neutral radical form. On the basis of a variety of reaction pathways and product profiles observed in the present and previous studies, the interplay between guanine structure, base pairing, and singlet oxygenation and its biological implications are discussed.
在 DNA 中，鸟嘌呤最容易受到外源性和内源性产生的电子激发单线态氧 (O) 的氧化损伤。反应机制和产物结果强烈依赖于核碱基的离子化状态和结构环境。以前，暴露于单体 9-甲基鸟嘌呤自由基阳离子 (9MG，一种模型鸟嘌呤化合物) 中时，发现 O 会导致形成 8-过氧化物作为初始产物。本工作探讨了在由单电子氧化的 9-甲基鸟嘌呤-1-甲基胞嘧啶 [9MG·1MC] 组成的 Watson-Crick 碱基对中，9MG 和其脱氢中性形式 [9MG - H] 的 O 氧化。重点是将碱基对结构环境和碱基对内质子转移及其对鸟嘌呤自由基物种的单线态氧合作用的纠缠。使用电喷雾电离结合引导离子束串联质谱法研究了气相中鸟嘌呤自由基物种的形成和反应。9MG 和 [9MG - H] 的 O 氧化都是放热的，无论是在孤立的单体中还是在碱基对中，都可以无障碍地进行。单参考和多参考理论都用于处理在自由基-O 相互作用中发生的自旋污染和多构型，并绘制了反应势能面以支持实验结果。该工作为不同电荷状态以及在没有和存在碱基配对的情况下，鸟嘌呤自由基的单线态氧合作用提供了全面的概况。所有结果都表明，在实验中，8-过氧化物是主要的氧化产物，而在中性自由基形式中，氧化变得稍微更有利。基于本研究和以前研究中观察到的各种反应途径和产物概况，讨论了鸟嘌呤结构、碱基配对和单线态氧合作用及其生物学意义之间的相互作用。
