Transient Intermediates by Photodissociation and UV-Vis Action Spectroscopy in the Gas Phase

通过气相光解离和紫外-可见作用光谱法制备瞬态中间体

• 批准号: 1951518
• 负责人: Frantisek Turecek
• 金额: $ 56万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1951518&HistoricalAwards=false
• 关键词: Transient; Intermediates; Photodissociation; UV; Vis

In this project funded by the Chemical Structure, Dynamics & Mechanisms B Program of the Chemistry Division, Professor Frantisek Turecek of the Department of Chemistry at University of Washington, Seattle, is developing new methods for the generation and spectroscopic studies of highly reactive ionized components of nucleic acids. These intermediates play a role in radical reactions causing DNA damage. The goal of this research is to exploit the spectroscopic properties and energetics of these short-lived intermediates for the understanding of the early stages of ionization damage in DNA. DNA ionization adversely affects individuals engaged in high-altitude travel, space exploration, and work with radioactive materials, as well as materials used for the future development of DNA computing. The project addresses natural as well as synthetic DNA components and lies at the interface of physical, organic, and computational chemistry. Another part of the project is aimed at determining structure and interactions in biomolecular complexes of protein and DNA components. The project is therefore well suited to the education of scientists at the forefront of chemical research. The research group is dedicated to provide high levels of education and professional training for graduate and undergraduate students, as well as science outreach to K-12 students.These studies address two areas of chemistry where highly reactive intermediates play an important role. In one part of these studies, gas-phase ion chemistry methods are used to generate DNA nucleobase, nucleoside, and oligonucleotide cation radicals, as well as those from unnatural hachimoji bases, and obtain their UV-Vis photodissociation (UVPD) action spectra. This provides the first interference-free electronic spectra of isolated cation radicals relevant to reactive intermediates formed in the initial stages of DNA ionization damage. Advanced methods of ion chemistry are employed to generate radical intermediates that include multistage collision-induced electron transfer in transition metal complexes, which is an oxidative process, and electron-transfer dissociation of multiply charged non-covalent complexes, which is a reductive process. Cation-radicals of 61 amino-acid encoding DNA trinucleotides are generated and characterized to establish the DNA code of vulnerability to ionization damage and radical-driven rearrangements. The experimental studies are supported and complemented by large-scale computations, including Born-Oppenheimer molecular dynamics, ab initio thermodynamics, RRKM (Rice–Ramsperger–Kassel–Marcus) kinetics, excited electronic states, and vibronic spectra. Another part of these studies is aimed at developing new photosensitive tags to be incorporated into specific amino acid residues and utilized for photodissociative cross linking in gas-phase complexes of peptide ions with nucleosides. Tandem mass spectrometry is used to determine the crosslink sites in the photoproduct ions. The experimental studies are aided and complemented by BOMD (Born-Oppenheimer molecular dynamics) trajectory calculations to identify low-free energy conformers and track the dynamics of non-covalent interactions in the complexes.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学结构资助的该项目中，化学部的动力学和机制B计划，西雅图华盛顿大学化学系教授Frantisek Turecek教授正在开发用于高度反应性电离成分的核酸成分的生成和光谱研究的新方法。这些中间体在导致DNA损伤的根部反应中起作用。这项研究的目的是利用这些短寿命中间体的光谱特性和能量学，以理解DNA中电离损伤的早期阶段。 DNA电离对从事高空旅行，太空探索以及使用放射性材料的个人以及用于DNA计算的未来开发的材料的个人。该项目涉及自然和合成DNA成分，并且位于物理，有机和计算化学的界面。该项目的另一部分旨在确定蛋白质和DNA成分的生物分子复合物中的结构和相互作用。因此，该项目非常适合在化学研究的最前沿的科学家教育。该研究小组致力于为研究生和本科生提供高水平的教育和专业培训，以及对K-12学生的科学宣传。这些研究涉及化学方面的两个领域，高反应性中间体发挥了重要作用。在这些研究的一部分中，使用气相化学方法来产生DNA核碱基，核苷和寡核苷酸阳离子自由基，以及来自非天然hachimoji碱基的DNA核苷酶，并获得其UV-VIS光发射（UVPD）动作光谱。这提供了与DNA电离损伤初始阶段形成的反应性中间体相关的分离阳离子自由基的第一个无干扰电子光谱。采用高级离子化学方法来产生自由基中间体，其中包括多阶段碰撞诱导的电子转移在过渡金属复合物中，这是氧化物过程，以及对多个带电的非共价复合物的电子转移分离，这是一个减少的过程。产生并表征了61个氨基酸编码DNA三核苷酸的阳离子 - 激进分子，以建立对电离损伤和自由基驱动重排的DNA脆弱性。实验研究得到了大规模计算的支持和完成，包括出生的分子动力学，初始热力学，RRKM（水稻 - ramsperger-kassel – marcus）动力学，激发的电子状态和振动光谱。这些研究的另一部分旨在开发新的光敏标签，以掺入特定的氨基酸残基中，并用于在肽离子与核平面的肽离子气相复合物中的光解剖交叉连接。串联质谱法用于确定光产物离子中的交联位点。 The experimental studies are aided and completed by BOMD (Born-Oppenheimer molecular dynamics) trajectory calculations to identify low-free energy conformers and track the dynamics of non-covalent interactions in the complexes.This award reflects NSF's statutory mission and has been deemed precious of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

项目成果

Resolution of Identity in Gas-Phase Dissociations of Mono- and Diprotonated DNA Trinucleotide Codons by 15 N-Labeling and Computational Structure Analysis

通过 15 N 标记和计算结构分析解析单质子化和二质子化 DNA 三核苷酸密码子气相解离的同一性

• DOI: 10.1021/jasms.2c00194
• 发表时间: 2022
• 期刊: Journal of the American Society for Mass Spectrometry
• 影响因子: 3.2
• 作者: Wan, Jiahao;Brož, Břetislav;Liu, Yue;Huang, Shu R.;Marek, Aleš;Tureček, František
• 通讯作者: Tureček, František

Low‐scale syringe‐made synthesis of 15 N‐labeled oligonucleotides

低规模注射器合成 15 个 N 标记寡核苷酸

• DOI: 10.1002/jlcr.4000
• 发表时间: 2022
• 期刊: Journal of Labelled Compounds and Radiopharmaceuticals
• 影响因子: 1.8
• 作者: Brož, Břetislav;Tureček, František;Marek, Aleš
• 通讯作者: Marek, Aleš

UV‐vis spectroscopy of gas‐phase ions

气相离子的紫外可见光谱

• DOI: 10.1002/mas.21726
• 发表时间: 2023
• 期刊: Mass Spectrometry Reviews
• 影响因子: 6.6
• 作者: Tureček, František

Flying DNA Cation Radicals in the Gas Phase: Generation and Action Spectroscopy of Canonical and Noncanonical Nucleobase Forms

气相中飞行的 DNA 阳离子自由基：规范和非规范核碱基形式的生成和作用光谱

• DOI: 10.1021/acs.jpcb.1c03674
• 发表时间: 2021
• 期刊: The Journal of Physical Chemistry B
• 作者: Tureček, František

Radical Cascade Dissociation Pathways to Unusual Nucleobase Cation Radicals

异常核碱基阳离子自由基的自由基级联解离途径

• DOI: 10.1021/jasms.2c00098
• 发表时间: 2022
• 期刊: Journal of the American Society for Mass Spectrometry
• 影响因子: 3.2
• 作者: Zima, Václav;Liu, Yue;Tureček, František
• 通讯作者: Tureček, František