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

在这个由化学部化学结构、动力学和机理B项目资助的项目中，西雅图华盛顿大学化学系的Frantisek Turecek教授正在开发新的方法，用于核酸的高活性电离成分的生成和光谱研究。这些中间体在引起DNA损伤的自由基反应中起作用。本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来了解DNA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。该项目涉及自然和合成DNA成分，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组分的生物分子复合物的结构和相互作用。因此，该项目非常适合对处于化学研究前沿的科学家进行教育。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。这些研究涉及两个化学领域，其中高活性中间体起着重要作用。其中一部分研究采用气相离子化学方法生成DNA核碱基、核苷和寡核苷酸阳离子自由基，以及来自非天然八果碱的阳离子自由基，并获得其紫外-可见光解（UVPD）作用谱。这提供了与DNA电离损伤初始阶段形成的活性中间体相关的孤立阳离子自由基的第一个无干扰电子谱。采用先进的离子化学方法生成自由基中间体，包括过渡金属配合物中多阶段碰撞诱导的电子转移，这是一个氧化过程，以及多电荷非共价配合物的电子转移解离，这是一个还原过程。编码DNA三核苷酸的61个氨基酸产生了阳离子自由基，并对其进行了表征，以建立易受电离损伤和自由基驱动重排的DNA代码。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 - ramspberger - kassel - marcus）动力学、激发态和振动谱。这些研究的另一部分旨在开发新的光敏标签，将其结合到特定的氨基酸残基中，并用于肽离子与核苷气相配合物的光解交联。串联质谱法用于测定光产物离子中的交联位点。实验研究得到BOMD （Born-Oppenheimer分子动力学）轨迹计算的辅助和补充，以确定低自由能构象并跟踪配合物中非共价相互作用的动力学。该奖项反映了美国国家科学基金会的法定使命，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。

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.