Collision Cross Section of a Small Molecule Determined by its Polarizability rather than its Mass and Shape

Abstract

Abstract The rotationally averaged collision cross section (CCS), measured by ion mobility mass spectrometry (IM-MS), facilitates the identification of various types of biomolecules. Thus far, the CCS value is known to depend on the shape and size of the molecule, while other physiochemical quantities for determining the CCS values are yet to be explored. In this study, using quantum chemistry and 197 model compounds, we discovered and validated that the CCS value primarily depends on the polarizability of the molecule, a quantity representing both the spatial size and dipole-dipole interaction with buffer gas molecules. Contrary to popular belief, at a constant polarizability, a molecule’s CCS value is completely independent of its mass (m/z) and shape (ovality). The findings of this study deepened our understanding of the CCS values of small molecules, and their application will considerably improve the CCS prediction model accuracy.