碰撞激活诱导的双势阱势能面可以实现9-甲基-8-氧鸟嘌呤-9-甲基腺嘌呤碱基对阳离子自由基的质子转移  

Development of a Double-Well Potential upon Collisional Activation that Facilitates Proton Transfer in 9-Methyl-8-oxoguanine–9-Methyladenine Base-Pair Radical Cation

作　　者：May Myat Moe 刘剑波 May Myat Moe;Jianbo Liu(Department of Chemistry and Biochemistry,Queens College of the City University of New York,NY 11367,USA;The Ph.D.Program in Chemistry,the Graduate Center of the City University of New York,NY 10016,USA)

机构地区：[1]美国纽约城市大学皇后学院化学与生物化学系,纽约11367 [2]美国纽约城市大学研究生院,纽约10016

出　　处：《Chinese Journal of Chemical Physics》2024年第2期330-340,I0022-I0039,I0104,共30页化学物理学报（英文）

基　　金：This work was supported by National Science Foundation of USA(Grant No.CHE 1856362).

摘　　要：8-氧鸟嘌呤(OG)是最常见的核碱基氧化损伤,它在复制过程中可以用Hoogsteen的模式与腺嘌呤(A)错误配对.0G.A碱基对不仅可以诱发G·C→T·A的颠换突变,而且由于OG的电离势和氧化电位低于天然DNA碱基更容易受到电离辐射和单电子氧化的影响,本文报道了[9MOG·9MA]^(·+)碱華对阳离子自由基的形成.和碰撞诱导解离,该碱基对利用9-甲基8-氧鸟嘌呤(9MOG)和9-甲基腺嘌呤(9MA)模拟相对应的核苷酸.实验通过电喷雾产生Cu(Ⅱ)碱基复合物继之以氧化分离产生[9MOG·9MA]^(·+),并使用导向离子束串级质谱仪检测[9MOG·9MA]^(·+)的碰撞诱导解离、通过测量在不同碰撞能量下的解离产物和反应截面,可以得出[9MOG-H]+[9MA+H]^(+)(主要解离通道)和9MOG^(·+)+9MA(次要通道)的0 K解离阈能分别为1.8和1.65 eV.使用密度泛函理论对[9MOG·9MA]^(·+)的结构计算发现其所有重要构象都发生了质子转移生成[9MOG-H]^(·)·[9MA+H]^(+).另一方面,9MOG^(·+)+9MA的解离通道却需要9MOG^(·+)9MA作为中间体.看似矛盾的结果可以用碰撞活化后反应势能面上出现的双重势阱和由此触发的激发态质子转移平衡([9MOG-H]^(·)·[9MA+H]^(+))^(*)→←(9MOG6(·+)·9MA)^(*)来解释.本文实验和理论研究揭示了这种生物学上重要的非规范碱基对如何在氧化和电离损伤时发生解离.8-Oxoguanine(OG)is the most common oxidatively generated nucleobase damage and can mispair with adenine(A)in Hoogsteen mode during replication.Besides introducing the G·C→T·A transversion mutation,the OG·A base pair is vulnerable to ionizing radiation and one-electron oxidation owing to the lower ionization and oxidation potentials of OG than natural DNA nucleobases.Herein,we report the formation and collision-induced dissociation(CID)of the radical cation of a model base pair consisting of nucleoside-mimicking 9-methyl-8-oxoguanine(9MOG)and 9-methyladenine(9MA).The[9MOG·9MA]^(•+) radical cation is formed in the gas phase by redox-separation of electrospray ionization-produced CuII-nucleobase complexes,and its CID is examined using guided-ion beam tandem mass spectrometry.Measurement included kinetic energy-dependent dissociation product ions and cross sections,from which the product pairs of[9MOG–H]^(•)+[9MA+H]^(+)(major dissociation channel)and 9MOG^(•+)+9MA(minor)were detected with 0 K dissociation threshold energies of 1.8 and 1.65 eV,respectively.The[9MOG·9MA]^(•+) structures were examined using density functional theory,and important conformations were all featured by complete intra-base pair proton transfer as[9MOG–H]^(•)·[9MA+H]^(+).On the other hand,the production of 9MOG^(•+)+9MA in dissociation required a 9MOG^(•+)·9MA intermediate.The results were rationalized by the discovery of a double-well potential that evolves on the reaction potential energy surface of the collisionally activated base pair,leading to the proton-transfer equilibrium of excited([9MOG–H]^(•)·[9MA+H]^(+))^(*)→←(9MOG^(•+)·9MA)^(*).The combined experimental and theoretical work provides insight into the less intuitive aspects of this biologically-important,non-canonical base pair,especially its opening upon oxidative and ionization damage.

关 键 词：碱基对阳离子自由基 碰撞诱导解离 碱基对内质子转移 反应势能面 电喷雾电离质谱 导向离子束散射 

分 类 号：O62[理学—有机化学]