Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences , ETH Zurich , Zurich 8093 , Switzerland.
Anal Chem. 2019 May 21;91(10):6624-6631. doi: 10.1021/acs.analchem.9b00541. Epub 2019 Apr 30.
Taken individually, chemical labeling and mass spectrometry are two well-established tools for the structural characterization of biomolecular complexes. A way to combine their respective advantages is to perform gas-phase ion-molecule reactions (IMRs) inside the mass spectrometer. This is, however, not so well developed because of the limited range of usable chemicals and the lack of commercially available IMR devices. Here, we modified a traveling wave ion mobility mass spectrometer to enable IMRs in the trapping region of the instrument. Only one minor hardware modification is needed to allow vapors of a variety of liquid reagents to be leaked into the trap traveling wave ion guide of the instrument. A diverse set of IMRs can then readily be performed without any loss in instrument performance. We demonstrate the advantages of implementing IMR capabilities in general, and to this quadrupole-ion mobility-time-of-flight (Q-IM-TOF) mass spectrometer in particular, by exploiting the full functionality of the instrument, including mass selection, ion mobility separation, and post-mobility fragmentation. The potential to carry out gas-phase IMR kinetics experiments is also illustrated. We demonstrate the versatility of the setup using gas-phase IMRs of established utility for biological mass spectrometry, including hydrogen-deuterium exchange, ion-molecule proton transfer reactions, and covalent modification of DNA anions using trimethylsilyl chloride.
单独来看，化学标记和质谱分析是两种用于生物分子复合物结构特征分析的成熟工具。一种结合它们各自优势的方法是在质谱仪内进行气相离子-分子反应（IMR）。然而，由于可用化学物质的范围有限以及缺乏商业可用的 IMR 设备，这种方法的发展并不完善。在这里，我们修改了飞行波离子淌度质谱仪，以使其能够在仪器的捕获区域内进行 IMR。只需进行一项较小的硬件修改，就可以将各种液体试剂的蒸气泄漏到仪器的捕获飞行波离子导中。然后，可以毫不损失仪器性能地轻松进行多种 IMR。我们展示了在一般情况下，特别是在四极杆-离子淌度-飞行时间（Q-IM-TOF）质谱仪中实现 IMR 功能的优势，充分利用了仪器的全部功能，包括质量选择、离子淌度分离和淌度后碎片化。还说明了进行气相 IMR 动力学实验的潜力。我们使用生物质谱学中已建立的有用的气相 IMR 来演示该设置的多功能性，包括氢-氘交换、离子-分子质子转移反应以及使用三甲基氯硅烷对 DNA 阴离子的共价修饰。
