Interaction of Vacuum UV radiation (6 - 12 eV) with complex DNA targets

真空紫外线辐射 (6 - 12 eV) 与复杂 DNA 靶标的相互作用

• 批准号: 281049597
• 负责人: Professor Dr. Ilko Bald
• 金额: --
• 依托单位: Institut für Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/281049597?language=en
• 关键词: Interaction; Vacuum; UV; radiation; 12

The interaction of UV radiation with living organisms can lead for instance to mutations within the genome. The photophysics associated with the lowest pi-pi* transition (around 4.8 eV or 260 nm) in DNA nucleobases, which can result for example in the formation of thymine dimers, was studied in great detail during the last 10 - 15 years. The excitation of DNA at energies as low as 6 eV can already result in DNA strand breaks, which become the dominant form of DNA radiation damage at photon energies above the ionization threshold (> 8 - 9 eV). However, the processes leading to DNA strand breaks are barely explored. The aim of the present proposal is a detailed characterization of the excitation/ionization below and right above the ionization threshold of the DNA nucleobases (6 - 12 eV) and the quantification of the resulting DNA strand breakage. Oligonucleotides with well-defined sequences up to about 15 nucleotides will be studied both experimentally and theoretically to reveal the influence of DNA sequence and local environment on the vacuum UV (VUV) photon-induced DNA strand breakage. To approach this problem, the absolute cross sections for DNA strand breakage will be determined as a function of nucleotide sequence and photon energy using synchrotron radiation. A recently developed DNA origami based technique will be used to provide the target oligonucleotides, while analysis by atomic force microscopy (AFM) enables the determination of strand break cross sections. To further explore the mechanism of the photo-induced DNA strand breakage and its sequence dependence, the ionization potential (IP) of the respective DNA sequences will be determined by irradiation of gas phase oligonucleotide ions with synchrotron radiation in the VUV range in a tandem mass spectrometry setup. In parallel the IPs of oligonucleotides will be determined computationally using state-of-the-art electronic structure methods. Additionally, the ionization cross sections and the relative stability of ionized DNA stacks will be calculated from first principles. The joint experimental and theoretical approach will reveal the influence of DNA primary and secondary structure and environment on DNA excitation, ionization and strand breakage. The applied innovative methods and the obtained results can contribute to an optimization of tumor radiation therapy and will have implications also for related fields such as DNA charge transport.

紫外线辐射与生物体的相互作用可能导致例如基因组内的突变。在过去的10 - 15年里，人们对DNA核碱基中最低的π-π * 跃迁（约4.8 eV或260 nm）相关的电子物理学进行了非常详细的研究，这可能导致例如胸腺嘧啶二聚体的形成。在低至6 eV的能量下激发DNA已经可以导致DNA链断裂，这在高于电离阈值（> 8 - 9 eV）的光子能量下成为DNA辐射损伤的主要形式。然而，导致DNA链断裂的过程几乎没有探索。本提案的目的是详细表征低于和正好高于DNA核碱基的电离阈值（6 - 12 eV）的激发/电离以及对所产生的DNA链断裂进行定量。本文将从实验和理论两个方面研究具有最多约15个核苷酸的明确序列的寡核苷酸，以揭示DNA序列和局部环境对真空紫外（VUV）光子诱导的DNA链断裂的影响。为了解决这个问题，DNA链断裂的绝对截面将被确定为核苷酸序列和光子能量的函数，使用同步辐射。最近开发的基于DNA折纸的技术将用于提供靶寡核苷酸，而通过原子力显微镜（AFM）的分析使得能够确定链断裂横截面。为了进一步探索光诱导DNA链断裂的机制及其序列依赖性，将通过在串联质谱装置中用VUV范围内的同步辐射照射气相寡核苷酸离子来确定相应DNA序列的电离势（IP）。同时，将使用最先进的电子结构方法计算确定寡核苷酸的IP。此外，电离截面和电离的DNA堆栈的相对稳定性将从第一原理计算。实验和理论相结合的方法将揭示DNA的一级和二级结构和环境对DNA的激发，电离和链断裂的影响。所应用的创新方法和所获得的结果可以有助于优化肿瘤放射治疗，并将对相关领域如DNA电荷传输产生影响。

项目成果

Long-Range Corrected DFT Meets GW: Vibrationally Resolved Photoelectron Spectra from First Principles.

• DOI: 10.1021/acs.jctc.5b00820
• 发表时间: 2015-10
• 期刊: Journal of chemical theory and computation
• 影响因子: 5.5
• 作者: Lukas Gallandi;T. Körzdörfer

Vacuum-UV and Low-Energy Electron-Induced DNA Strand Breaks - Influence of the DNA Sequence and Substrate.

• DOI: 10.1002/cphc.201801152
• 发表时间: 2019-03
• 期刊: Chemphyschem : a European journal of chemical physics and physical chemistry
• 作者: Stefanie Vogel;Kenny Ebel;R. Schürmann;C. Heck;T. Meiling;A. Milosavljević;A. Giuliani;I. Bald