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.
Phys Chem Chem Phys. 2022 Apr 20;24(16):9263-9276. doi: 10.1039/d2cp00312k.
It has been shown previously in protonated, deprotonated and ionized guanine-cytosine base pairs that intra-base pair proton transfer from the N1-H at the Watson-Crick edge of guanine to the complementary nucleobase prompts non-statistical dissociation of the base-pair system, and the dissociation of a proton-transferred base-pair structure is kinetically more favored than that of the starting, conventional base-pair structure. However, the fundamental chemistry underlying this anomalous and intriguing kinetics has not been completely revealed, which warrants the examination of more base-pair systems in different structural contexts in order to derive a generalized base-pair structure-kinetics correlation. The purpose of the present work is to expand the investigation to the non-canonical homodimeric and heterodimeric radical cations of 9-methylguanine (9MG) and 9-methyl-8-oxoguanine (9MOG), , [9MG·9MG]˙, [9MOG·9MG]˙ and [9MOG·9MOG]˙. Experimentally, collision-induced dissociation tandem mass spectrometry coupled with an electrospray ionization (ESI) source was used for the formation of base-pair radical cations, followed by detection of dissociation product ions and cross sections in the collisions with Xe gas under single ion-molecule collision conditions and as a function of the center-of-mass collision energy. Computationally, density functional theory and coupled cluster theory were used to calculate and identify probable base-pair structures and intra-base pair proton transfer and hydrogen transfer reactions, followed by kinetics modeling to explore the properties of dissociation transition states and kinetic factors. The significance of this work is twofold: it provides insight into base-pair opening kinetics in three biologically-important, non-canonical systems upon oxidative and ionization damage; and it links non-statistical dissociation to intra-base pair proton-transfer originating from the N1-H at the Watson-Crick edge of 8-oxoguanine, enhancing understanding towards the base-pair fragmentation assisted by proton transfer.
先前已经在质子化、去质子化和离子化的鸟嘌呤-胞嘧啶碱基对中表明，从鸟嘌呤 Watson-Crick 边缘的 N1-H 到互补核碱基的碱基对内质子转移促使碱基对系统的非统计解离，并且质子转移碱基对结构的解离在动力学上比起始的常规碱基对结构更有利。然而，这种异常和有趣的动力学背后的基本化学尚未完全揭示，这需要在不同的结构背景下检查更多的碱基对系统，以得出广义的碱基对结构-动力学相关性。本工作的目的是将研究扩展到 9-甲基鸟嘌呤（9MG）和 9-甲基-8-氧鸟嘌呤（9MOG）的非规范同源二聚体和杂二聚体自由基阳离子，即[9MG·9MG]˙，[9MOG·9MG]˙和[9MOG·9MOG]˙。实验上，采用碰撞诱导解离串联质谱与电喷雾电离（ESI）源联用，形成碱基对自由基阳离子，然后在单离子-分子碰撞条件下和作为质心碰撞能量函数，用 Xe 气体检测解离产物离子和截面。理论上，采用密度泛函理论和耦合簇理论计算和识别可能的碱基对结构以及碱基对内质子转移和氢转移反应，然后进行动力学建模以探索解离过渡态的性质和动力学因素。这项工作的意义有两个方面：它提供了在氧化和电离损伤下三个重要的、非规范的系统中碱基对打开动力学的深入了解；并将非统计解离与源自 8-氧鸟嘌呤 Watson-Crick 边缘的 N1-H 的质子转移联系起来，增强了对质子转移辅助碱基对断裂的理解。
