Pushing the limits of mass spectrometry for the separation and identification of analytes using ion mobility and mass accuracy

The structural characterization and elucidation of compounds is one of the main fields of the physical chemistry that is based on the determination of the spatial organization of the compound particles. From the available techniques allowing the investigation of the three-dimensional structure of compounds, ion mobility mass spectrometry has undeniable advantages for the structural studies in the gas phase. The reconciliation of ion mobility mass spectrometry experiment and theoretical simulations is often considered for de-novo structure elucidation based on the determination of the experimental and theoretical collision cross section values. However, this approach requires accurate experimental determination and confident prediction of collision cross section to ensure relevant structure characterization based on collision cross section values matching. Here, we report in this work the development of analytical strategies for a better understanding of structural characterization of molecular systems by pushing the current limits of mass spectrometry and ion mobility mass spectrometry. These new strategies have allowed increasing the confidence level of the structure characterisation involving the increase of ion mobility separation and the refinement of the experimental collision cross section determination by refining the raw data reprocessing. New structure descriptors are also be investigated for helping the reconciliation of experimental and predicted collision cross section values. Finally, the reliability of ion mobility mass spectrometry for the investigation of native physicochemical properties is discussed in regard with data obtained from capillary zone electrophoresis. This work highlights that the use of ion mobility mass spectrometry for structural characterization and de-novo structure elucidation has a bright future.