Advanced X-ray Spectroscopy for Biological Chemistry

X射线吸收光谱(XAS)使用同步辐射来探测几乎任何基质中目标元素周围其他原子的电子结构和物理排列。虽然XAS已经很成熟，在一系列学科中带来了重要的见解，但与任何方法一样，它有限制其实用性的固有限制。在这项提案中，我计划推动这项重要的同步加速器技术的发展，并将这些进展提供给更广泛的研究社区。 XAS的四个局限性包括：(1)较差的键长分辨率；(2)很少或没有几何信息；(3)较差的光谱分辨率；(4)无法获得极低浓度。我以前的工作探索了克服限制(1)和(2)的方法；在这里，我专注于通过一套统称为高级X射线光谱分析(AXS)的方法来解决限制(3)和(4)。AXS方法是光子输入/光子输出光谱仪，其中入射和发射的光子都以非常高的能量分辨率进行测量。所谓的高能量分辨率荧光检测(HERFD)克服了固有的光谱展宽，这是由于电子被激发时产生的核心空穴的寿命造成的。相反，HERFD对发射时产生的芯孔的寿命要长得多很敏感。HERFD产生的精致锐利的光谱允许对化学形式的物种形成和电子结构的研究更敏感。同时，极大地改善了背景抑制，允许进入超稀释浓缩区域，这是一个不同寻常的光谱双赢！ 目标和科学方法：我寻求开发软(2-5keV)和硬(5keV)X射线能量区域的AXS方法，将其从高度专业化的技术转变为主流技术。我通过使用AXS的有针对性的研究项目来实现这一点，这些项目符合我对生物无机和生物化学的职业兴趣。这些研究包括研究生命所必需的元素，如钼、钨和铜；以及有毒元素，如砷和汞，以及它们与基本元素硒的关系。 新颖性和预期意义：AXS提供的机遇不亚于革命性，有望改变XAS在环境和健康科学等许多学科中的使用。由于AXS设施现在正在全球同步加速器设施中涌现，我们拟议的工作将使加拿大社区成为该领域的世界领导者之一，并为处于同步加速器技术开发前沿的高素质人员提供无与伦比的跨学科培训机会。

X-ray absorption spectroscopy (XAS) uses synchrotron radiation to probe the electronic structure and physical arrangement of other atoms around a target element in almost any matrix. While XAS is well-established, bringing important insights in a range of disciplines, like any method it has inherent limitations that curb its utility. In this proposal I lay out plans to push the boundaries of this important synchrotron technique and to make these advances available to the wider research community. Four limitations of XAS include: (1) poor bond-length resolution; (2) little or no geometrical information; (3) poor spectroscopic resolution; and (4) lack of access to very low concentrations. My previous work explored methods of overcoming limitations (1) and (2); here I focus on addressing limitations (3) and (4), through a suite of methods known collectively as advanced X-ray spectroscopy (AXS). AXS methods are photon-in/photon-out spectroscopies, where both incident and emitted photons are measured with very high energy resolution. The so-called high energy resolution fluorescence detection (HERFD) overcomes the inherent broadening of the spectra, which is due to the lifetime of the core-hole created when an electron is excited. Instead HERFD is sensitive to the much longer lifetime of the core-hole created upon emission. The exquisitely sharper spectra that result from HERFD allow greater sensitivity to speciation of chemical forms and studies of electronic structure. At the same time, the enormously improved background rejection allows access to the ultra-dilute concentration regime an unusual spectroscopic win-win! OBJECTIVES AND SCIENTIFIC APPROACH: I seek to develop AXS methodology in both tender (2-5 keV) and hard (>5keV) X-ray energy regimes, moving it from a highly-specialized to a mainstream technique. I achieve this through targeted research projects using AXS in my career interests of bioinorganic and biological chemistry. These include studies of elements essential for life such as Mo, W, and Cu; and of toxic elements such as As and Hg, and their relationship with the essential element Se. NOVELTY AND EXPECTED SIGNIFICANCE: The opportunities afforded by AXS are no less than revolutionary, poised to transform the use of XAS in environmental and health science, amongst many other disciplines. Since AXS facilities are now emerging at synchrotron facilities worldwide, our proposed work will position the Canadian community to be among the world leaders in this area, and provide unparalleled opportunities for cross-disciplinary training of highly qualified personnel at the forefront of synchrotron technique development.