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

这项研究的目的是促进我们对化学环境如何影响电子与生物分子结合的理解。电子附着过程在生物材料的辐射损伤中起着重要的作用。特别是，由局部分子(主要是水)电离释放的电子在附着到DNA的核碱基之前，可能会在一系列碰撞中损失能量。生成的负离子可能是不稳定的，因此产生活性物种的碎片。DNA中高密度的这种解离事件构成了一个聚集性病变，被认为是突变和癌症的关键先兆。因此，详细了解电子如何附着在生物分子上以及所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必不可少的。此外，表征低能电子与特定生物分子的相互作用可以揭示用掺杂剂操纵它们的化学环境如何影响它们的辐射敏感性，这在放射治疗和辐射保护方面具有重要应用。该项目将集中在开发一种原创的实验系统，以精确定义的能量(约1 meV至15 eV)用电子照射氢键生物分子簇，并用质谱仪分析生成的阴离子。关键的优势、新颖性和挑战将在于应用极性物种在不均匀电场中的偏转(斯塔克偏转)，以便在与电子相互作用之前提供对目标团簇构型的特殊控制。到目前为止，与理论的直接比较一直受到实验中中性星团大小扩散的限制。该计划将与领先的理论家(内布拉斯加州大学的戈芬基尔、俄亥俄大学和法布里坎特)密切合作，开创模拟电子从团簇分子散射/附着到团簇分子的新方法。因此，我们将首次在等效实验和计算中探讨电子与特定中性团簇的相互作用。最初的生物分子目标将是由水分子、DNA碱基和相关的氮苯分子吡啶组成的络合物。对引发生物材料辐射损伤的分子尺度过程的了解，最近推动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已经揭示了特定阴离子的电子附着点和碎裂模式的详细信息。然而，氢键可以极大地改变分子的电子亲和力，并引入从阴离子状态到能量耗散和电子损失的新途径。没有尺寸选择的生物分子团簇和浓缩生物分子上的实验的解释分别由于缺乏对目标的精确知识和介电表面电荷而受到影响。大小选定的中性团簇提供了一个强大的测试案例来探索氢键的影响，特别是通过研究关键生物分子产生的片段阴离子与相关水分子的精确数量的函数。总之，我的目标是发展一个独特的实验方案，并提供强有力的理论支持，以促进我们对尺寸选定的中性团簇中的电子附着过程作为模型多分子系统的理解。这项研究将有助于弥合在理解孤立分子和凝聚材料中的辐射诱导过程与在纳米尺度上模拟和潜在修改生物损伤过程方面的应用之间的复杂性差距。

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.