Collaborative Research: Tunable HDX and Ion-Molecule Interactions Using Doped-Gas Ion Mobility-Mass Spectrometry

在化学系化学测量和成像项目的支持下，Brian H. Clowers（华盛顿州立大学）和Christopher J. Hogan教授（明尼苏达大学）正在努力提高离子迁移谱（IMS）的性能和能力，IMS是一种化学分析方法，其应用范围从机场爆炸物的快速筛查到与健康和患病生物体相关的生物分子的结构和功能的详细了解。 该团队正在设计在国际监测系统仪器内使用与溶剂分子和其他气体添加剂的选择性相互作用的方法，以提高分离和识别复杂混合物中分子的能力。 通过将这些方法与质谱（一种强大的互补技术）和新的计算工具相结合，该研究旨在提供一种广泛适用于化学分析的创新工作流程。参与这项研究的学生获得独特的跨学科培训，并有机会在学习过程中进行“非学科”工作。 最近，Clowers教授和Hogan教授通过将气相离子和有机蒸气改性剂引入离子迁移率系统，证明了通过选择性相互作用可以增强分离因子。他们现在寻求更详细地了解离子-蒸气复合物的潜在相互作用，以预测并扩大IM-MS和串联IM实验的使用。他们的方法使用创新的多维离子迁移率/氢氘交换质谱策略和气相离子中性相互作用和蒸气吸收的第一原理建模。主要目的是确定（1）气相缔合的热力学是否依赖于氨基酸和简单肽离子的化学功能性;（2）结合的程度是否可以外推作为表现出已知二级结构的较大的多电荷离子的表征工具;（3）聚集动力学是否定量地描述高场和不对称波形实验中离子的行为;和（4）如果分子动力学可以准确地描述溶剂化离子传输。这个奖项反映了NSF的法定使命，并已被认为是值得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的支持。

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, the research groups of Professor Brian H. Clowers (Washington State University) and Professor Christopher J. Hogan (University of Minnesota) are working to improve the performance and capabilities of ion mobility spectrometry (IMS), a chemical analysis method with applications ranging from rapid screening for explosives in airports to detailed insight into the structure and function of biomolecules associated with healthy and diseased organisms. The team is devising means of using selective interactions with solvent molecules and other gaseous additives within the IMS instrument in order to enhance the ability to separate and identify molecules in complex mixtures. By combining these methods with mass spectrometry (a powerful complementary technique) and new computational tools, the research aims to provide an innovative workflow that is broadly applicable to chemical analysis. Students engaged in this research obtain unique interdisciplinary training enhanced by opportunities to work “out-of-discipline” as part of their studies. Research opportunities are also made available to undergraduate and high school students.Recently, Professors Clowers and Hogan have demonstrated enhanced separation factors through selective interactions between gas-phase ions and organic vapor modifiers introduced into ion mobility systems. They now seek to gain a more detailed understanding of the underlying interactions of ion-vapor complexes in order to predict and enable expanded use of IM-MS and tandem IM experiments. Their approach uses an innovative, multidimensional ion mobility/hydrogen-deuterium exchange mass spectrometry strategy and first-principles modeling of gas-phase ion-neutral interactions and vapor uptake. Primary aims are to determine (1) if thermodynamics of vapor association depend upon chemical functionality in amino acids and simple peptide ions; (2) if the extent of binding can be extrapolated as a characterization tool for larger, multiply charged ions exhibiting known secondary structure; (3) if clustering dynamics quantitatively describe the behavior of ions in high-field and asymmetric waveform experiments; and (4) if molecular dynamics can accurately describe solvated ion transport.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.