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计划的支持下，华盛顿州立大学的Brian H.Clowers教授和明尼苏达大学的Christopher J.Hogan教授的研究小组正在努力提高离子迁移率光谱(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选到详细了解与健康和患病生物相关的生物分子的结构和功能。该团队正在设计一种方法，在IMS仪器中使用与溶剂分子和其他气体添加剂的选择性相互作用，以增强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学(一种强大的补充技术)和新的计算工具相结合，这项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了独特的跨学科培训，作为他们学习的一部分，他们有机会进行“学科外”的工作。研究机会也为本科生和高中生提供。最近，Clowers和Hogan教授展示了通过在离子迁移率系统中引入气相离子和有机蒸气改进剂之间的选择性相互作用来增强分离系数。他们现在试图更详细地了解离子-蒸汽复合体的潜在相互作用，以便预测和扩大IM-MS和串联IM实验的使用。他们的方法采用了一种创新的多维离子迁移率/氢-氚交换质谱学策略，并对气相离子-中性相互作用和蒸汽吸收进行了第一原理建模。主要目的是确定(1)蒸气缔合热力学是否取决于氨基酸和简单多肽离子的化学功能；(2)结合程度是否可以外推为展示已知二级结构的较大、多电荷离子的表征工具；(3)聚集动力学是否能定量描述离子在高场和不对称波形实验中的行为；以及(4)分子动力学是否能准确描述溶剂化离子的传输。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.