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.

在这个由化学部化学结构、动力学机制B计划资助的项目中，西雅图华盛顿大学化学系的Frantisek Turecek教授正在开发用于产生和光谱研究核酸的高活性离子化组分的新方法。这些中间体在导致DNA损伤的自由基反应中发挥作用。本研究的目标是利用这些短寿命中间体的光谱特性和能量学来理解DNA中电离损伤的早期阶段。DNA电离对从事高空旅行、太空探索和放射性材料工作的个人以及用于DNA计算未来发展的材料产生不利影响。该项目涉及天然和合成DNA成分，并位于物理，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的结构和相互作用。因此，该项目非常适合化学研究前沿科学家的教育。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，并为K-12学生提供科学推广。这些研究涉及高活性中间体发挥重要作用的两个化学领域。在这些研究的一部分中，气相离子化学方法被用来产生DNA核碱基，核苷，和寡核苷酸阳离子自由基，以及那些从非天然八王子基地，并获得其紫外可见光解离（UVPD）的行动光谱。 这提供了第一个无干扰的电子光谱的孤立的阳离子自由基有关的活性中间体形成的DNA电离损伤的初始阶段。采用离子化学的先进方法来产生自由基中间体，其包括过渡金属络合物中的多级碰撞诱导电子转移，这是一种氧化过程，以及多电荷非共价络合物的电子转移解离，这是一种还原过程。产生并表征了编码DNA三核苷酸的61个氨基酸的阳离子自由基，以建立对电离损伤和自由基驱动的重排的脆弱性的DNA密码。实验研究得到了大规模计算的支持和补充，包括Born-Oppenheimer分子动力学，从头算热力学，RRKM（Rice-Ramsperger-Kassel-Marcus）动力学，激发电子态和振动光谱。这些研究的另一部分旨在开发新的光敏标签，以纳入特定的氨基酸残基，并用于肽离子与核苷的气相复合物中的光解离交联。串联质谱用于确定光产物离子中的交联位点。实验研究得到BOMD（Born-Oppenheimer molecular dynamics）轨道计算的辅助和补充，以识别低自由能构象并跟踪复合物中非共价相互作用的动力学。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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

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

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