Electron attachment to biomolecular clusters: probing the role of multiple scattering in radio-sensitivity.

电子附着在生物分子簇上：探讨多重散射在放射敏感性中的作用。

• 批准号: EP/J002577/1
• 负责人: Samuel Eden
• 金额: $ 78.79万
• 依托单位: The Open University
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FJ002577%2F1
• 关键词: Electron; attachment; biomolecular; clusters; probing

The aim of this fellowship is to advance our understanding of how the chemical environment affects electron attachment to biomolecules. Electron attachment processes play an important role in radiation damage to biological material. In particular, electrons released by the ionization of local molecules (mainly water) can lose energy in a series of collisions before attaching to nucleobases in DNA. The resultant negative ions may be unstable and hence fragment yielding reactive species. A high density of such dissociation events in DNA constitutes a clustered lesion, recognised as a key precursor to mutations and cancers. Detailed knowledge of how electrons attach to biomolecules and the stabilities of the resultant anionic states is therefore essential to understand radiation damage on the molecular scale. Moreover characterising low-energy electron interactions with specific biomolecules can inform how manipulating their chemical environment with dopants can affect their radio-sensitivity with important applications in radiotherapy and radiation protection.The project will be centred on the development of an original experimental system to irradiate hydrogen-bonded biomolecular clusters with electrons at precisely defined energies (around 1meV to 15eV) and analyse the resultant anions by mass spectrometry. The key strength, novelty, and challenge will lie in applying the deflection of polar species in inhomogeneous electric fields (Stark deflection) to provide exceptional control over the target cluster configurations before the interactions with electrons. To date, direct comparisons with theory have been limited by the spread of neutral cluster sizes in experiments. The programme will be carried out in close collaboration with leading theoreticians (Gorfinkiel, OU, and Fabrikant, University of Nebraska) pioneering new methods to simulate electron scattering from / attachment to molecules within clusters. Electron interactions with specific neutral clusters will therefore be probed in equivalent experiments and calculations for the first time. The initial biomolecular targets will be complexes comprising water molecules, DNA bases, and a related azabenzene molecule, pyridine. Understanding the molecular-scale processes that initiate radiation damage in biological material has recently motivated extensive research into low-energy electron interactions with biomolecules. Experimental and theoretical studies of gas-phase biomolecules have revealed detailed information about the electron attachment sites and fragmentation patterns of specific anions. However hydrogen bonding can dramatically change the electron affinities of molecules as well as introducing new pathways for energy dissipation and electron loss from anionic states. The interpretation of experiments on biomolecular clusters without size selection and on condensed biomolecules is compromised by the lack of precise knowledge of the target and by dielectric surface charging, respectively. Size-selected neutral clusters provide a powerful test case to probe the effects of hydrogen bonding, notably by studying fragment anion production from a key biomolecule as a function of the precise number of associated water molecules. In summary, my objective is to develop a unique programme of experiments with strong theoretical support to advance our understanding of electron attachment processes in size-selected neutral clusters as model multi-molecular systems. This research will help to bridge the complexity gap between understanding radiation-induced processes in isolated molecules and in condensed material, with applications in modelling and potentially modifying biological damage processes on the nanoscale.

该奖学金的目的是促进我们对化学环境如何影响电子附着到生物分子的理解。电子附着过程在生物材料的辐射损伤中起着重要作用。特别是，由局部分子（主要是水）电离释放的电子在附着到DNA中的核碱基之前会在一系列碰撞中失去能量。所得到的负离子可能是不稳定的，因此产生反应性物质的碎片。DNA中高密度的这种解离事件构成了聚集性病变，被认为是突变和癌症的关键前兆。因此，详细了解电子如何附着在生物分子上以及由此产生的阴离子状态的稳定性对于理解分子尺度上的辐射损伤是至关重要的。此外，表征低能电子与特定生物分子的相互作用可以告知掺杂剂如何操纵它们的化学环境，从而影响它们的辐射敏感性，这在放射治疗和辐射防护方面具有重要应用。该项目将集中于开发一个原始实验系统，以精确定义的能量用电子照射氢键生物分子簇（约1 meV至15 eV），并通过质谱法分析所得阴离子。关键的力量，新奇和挑战将在于应用极性物种在非均匀电场（斯塔克偏转）的偏转，以提供特殊的控制目标集群配置之前与电子的相互作用。到目前为止，与理论的直接比较受到实验中中性团簇大小分布的限制。该计划将与领先的理论家（Gorfinkiel，Nebraska大学的Gorfinkiel和Fabrikant）密切合作，开创新的方法来模拟电子从/附着到簇内分子的散射。因此，电子与特定的中性团簇的相互作用将首次在等效实验和计算中进行探测。最初的生物分子靶标将是包含水分子、DNA碱基和相关的氮杂苯分子吡啶的复合物。了解引发生物材料辐射损伤的分子尺度过程最近激发了对低能电子与生物分子相互作用的广泛研究。气相生物分子的实验和理论研究揭示了有关特定阴离子的电子附着位点和碎片模式的详细信息。然而，氢键可以显着改变分子的电子亲合势，以及引入新的途径，能量耗散和电子损失的阴离子状态。没有大小选择的生物分子簇和凝聚的生物分子上的实验的解释是妥协的目标和介电表面充电，分别缺乏精确的知识。大小选择的中性簇提供了一个强大的测试案例，以探测氢键的影响，特别是通过研究片段阴离子生产从一个关键的生物分子作为相关的水分子的精确数量的函数。总之，我的目标是开发一个独特的实验方案，强有力的理论支持，以促进我们的理解，在大小选择的中性集群模型多分子系统的电子附着过程。这项研究将有助于弥合理解孤立分子和凝聚材料中辐射诱导过程之间的复杂性差距，并应用于纳米尺度上的建模和潜在修改生物损伤过程。

项目成果

Electronic State Spectroscopy of Halothane As Studied by ab Initio Calculations, Vacuum Ultraviolet Synchrotron Radiation, and Electron Scattering Methods.

通过从头计算、真空紫外同步辐射和电子散射方法研究氟烷的电子态光谱。

• DOI: 10.1021/acs.jpca.5b05308
• 发表时间: 2015
• 期刊: The journal of physical chemistry. A
• 作者: Da Silva FF

Mapping the complex metastable fragmentation pathways of excited 3-aminophenol+

绘制激发的 3-氨基苯酚复杂的亚稳态裂解途径

• DOI: 10.1016/j.ijms.2019.05.006
• 发表时间: 2019
• 期刊: International Journal of Mass Spectrometry
• 影响因子: 1.8
• 作者: Bockova J

Thermal desorption effects on fragment ion production from multi-photon ionized uridine and selected analogues.

• DOI: 10.1039/d1ra01873f
• 发表时间: 2021-06-09
• 期刊: RSC advances
• 影响因子: 3.9

Multi-photon and electron impact ionisation studies of reactivity in adenine-water clusters

• DOI: 10.1016/j.ijms.2014.01.007
• 发表时间: 2014-05-15
• 期刊: INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
• 影响因子: 1.8
• 作者: Barc, B.;Ryszka, M.;Eden, S.
• 通讯作者: Eden, S.