Collision Cross Section Measurements Using Fourier Transform Ion Cyclotron Resonance Techniques

使用傅里叶变换离子回旋共振技术进行碰撞截面测量

• 批准号: 1904838
• 负责人: David Dearden
• 金额: $ 49.5万
• 依托单位: Brigham Young University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1904838&HistoricalAwards=false
• 关键词: Collision; Cross; Section; Measurements; Using

With support from the Chemical Measurement and Imaging program in the Chemistry Division, Professors David Dearden and Matthew Asplund of Brigham Young University and their students are devising a new approach to measuring the shapes of molecules, including the way that biological molecules like proteins are folded. While superb techniques exist for such measurements, those techniques require specialized instrumentation. This team is developing new techniques to extend these capabilities to an additional class of existing instrumentation with only minimal modification, making these measurements more widely available. Their approach may also offer enhanced performance for some applications. These measurements are important because just as a misshapen, misfolded parachute may not unfurl correctly, misfolded protein molecules (for example) do not function properly and are believed to be among the root causes of debilitating conditions like Alzheimer?s or Parkinson?s diseases. Sensitive detection of the shape is essential to understanding how molecules fit together and function, and what can go wrong at the molecular level. Students carrying out this work are trained in skills essential to the 21st century science that is the foundation of the U.S. economy.In this project, graduate and undergraduate students are developing techniques designed to measure the collision cross sections of gas phase ions, without requiring a dedicated ion mobility instrument. Two independent approaches to these measurements are taken. The first examines signal decay as ions are scattered out of a coherently-orbiting ensemble in a Fourier transform ion cyclotron resonance mass spectrometer (FTICR/MS). The decay rate (and the corresponding FTICR linewidth) depends on the collision cross section. The second approach measures the phase lag between the radiofrequency electric field used to excite the ions and the ion motion in the presence of a damping buffer gas. This approach overcomes mass-to-charge and energy limits that are inherent in the linewidth method. The utility of these techniques is demonstrated by examining problems in supramolecular chemistry and structural biochemistry. In the course of this work, graduate students are trained in advanced techniques for high performance mass spectrometry that are vital for the biotechnology industry and the emerging field of proteomics. Many of the talented undergraduate students engaged in this research subsequently pursue graduate studies. The instrumentation used in this study is also made available for undergraduate courses in general, analytical and physical chemistry at BYU, which is a significant supplier of B.S. chemistry and biochemistry students to U.S. graduate programs.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.

在化学系化学测量和成像项目的支持下，杨百翰大学的大卫·迪尔登（David Dearden）和马修·阿斯普伦德（Matthew Asplund）教授及其学生正在设计一种测量分子形状的新方法，包括蛋白质等生物分子的折叠方式。虽然此类测量存在精湛的技术，但这些技术需要专门的仪器。 该团队正在开发新技术，只需进行最少的修改即可将这些功能扩展到现有仪器的另一类，从而使这些测量得到更广泛的应用。 他们的方法还可以为某些应用程序提供增强的性能。 这些测量很重要，因为就像畸形、错误折叠的降落伞可能无法正确展开一样，错误折叠的蛋白质分子（例如）也无法正常发挥作用，并且被认为是导致阿尔茨海默氏症或帕金森氏症等衰弱疾病的根本原因。对形状的灵敏检测对于了解分子如何组合和发挥作用以及在分子水平上可能出现的问题至关重要。从事这项工作的学生接受了作为美国经济基础的 21 世纪科学所必需的技能培训。在这个项目中，研究生和本科生正在开发旨在测量气相离子碰撞截面的技术，而无需专用的离子淌度仪器。 采用两种独立的方法进行这些测量。第一个检查当离子从傅里叶变换离子回旋共振质谱仪 (FTICR/MS) 中的相干轨道系综中散射出来时的信号衰减。衰减率（以及相应的 FTICR 线宽）取决于碰撞截面。第二种方法测量用于激发离子的射频电场与阻尼缓冲气体存在下的离子运动之间的相位滞后。这种方法克服了线宽方法固有的质荷比和能量限制。通过检查超分子化学和结构生物化学中的问题证明了这些技术的实用性。在这项工作的过程中，研究生接受了高性能质谱先进技术的培训，这对于生物技术行业和新兴的蛋白质组学领域至关重要。 许多从事这项研究的优秀本科生随后继续攻读研究生。 本研究中使用的仪器也可用于杨百翰大学的普通、分析和物理化学本科课程，杨百翰大学是理学学士课程的重要供应商。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Ion Mobility and Fourier Transform Ion Cyclotron Resonance Collision Cross Section Techniques Yield Long-Range and Hard-Sphere Results, Respectively

离子淌度和傅里叶变换离子回旋共振碰撞截面技术分别产生长程和硬球结果

• DOI: 10.1021/jasms.2c00112
• 发表时间: 2022
• 期刊: Journal of the American Society for Mass Spectrometry
• 影响因子: 3.2
• 作者: Heravi, Tina;Arslanian, Andrew J.;Johnson, Spencer D.;Dearden, David V.
• 通讯作者: Dearden, David V.

Multi-CRAFTI: Relative Collision Cross Sections from Fourier Transform Ion Cyclotron Resonance Mass Spectrometric Line Width Measurements

Multi-CRAFTI：傅里叶变换离子回旋共振质谱线宽测量的相对碰撞截面

• DOI: 10.1021/jasms.1c00297
• 发表时间: 2022
• 期刊: Journal of the American Society for Mass Spectrometry
• 影响因子: 3.2
• 作者: Pope, Brigham L.;Joaquin, Daniel;Hickey, Jacob T.;Mismash, Noah;Heravi, Tina;Shrestha, Jamir;Arslanian, Andrew J.;Anupriya;Mortensen, Daniel N.;Dearden, David V.
• 通讯作者: Dearden, David V.

Halide Size-Selective Binding by Cucurbit[5]uril–Alkali Cation Complexes in the Gas Phase

气相中葫芦[5]uril-碱金属阳离子配合物的卤化物尺寸选择性结合

• DOI: 10.1021/acs.jpca.1c05060
• 发表时间: 2021
• 期刊: The Journal of Physical Chemistry A
• 作者: Heravi, Tina;Shen, Jiewen;Johnson, Spencer;Asplund, Matthew C.;Dearden, David V.
• 通讯作者: Dearden, David V.

Collision Cross-Section Measurements of Collision-Induced Dissociation Precursor and Product Ions in an FTICR-MS and an IM-MS: A Comparative Study

FTICR-MS 和 IM-MS 中碰撞诱导解离母离子和子离子的碰撞截面测量：比较研究

• DOI: 10.1021/jasms.2c00089
• 发表时间: 2022
• 期刊: Journal of the American Society for Mass Spectrometry
• 影响因子: 3.2
• 作者: Arslanian, Andrew J.;Mismash, Noah;Dearden, David V.
• 通讯作者: Dearden, David V.

Prototypical Allosterism in a Simple Ditopic Ligand: Gas-Phase Topologies of Cucurbit[n]uril· n -Alkylammonium Complexes Controlled by Binding in the Second Site

简单双位配体中的典型变构现象：由第二位点结合控制的葫芦[n]脲·n-烷基铵配合物的气相拓扑

• DOI: 10.1021/acs.jpca.2c01703
• 发表时间: 2022
• 期刊: The Journal of Physical Chemistry A
• 作者: Shrestha, Jamir;Porter, Savannah R.;Tinsley, Caleb;Arslanian, Andrew J.;Dearden, David V.
• 通讯作者: Dearden, David V.