Liu, ChangLe Blanc, J. C. YvesShields, JefryJaniszewski, John S.Ieritano, ChristianYe, Gene F.Hawes, Gillian F.Hopkins, W. ScottCampbell, J. Larry2020-10-262020-10-262015https://doi.org/10.1039/C5AN00842Ehttp://hdl.handle.net/10012/16472Understanding the mechanisms and energetics of ion solvation is critical in many scientific areas. Here, we present a methodlogy for studying ion solvation using differential mobility spectrometry (DMS) coupled to mass spectrometry. While in the DMS cell, ions experience electric fields established by a high frequency asymmetric waveform in the presence of a desired pressure of water vapor. By observing how a specific ion's behavior changes between the high- and low-field parts of the waveform, we gain knowledge about the aqueous microsolvation of that ion. In this study, we applied DMS to investigate the aqueous microsolvation of protonated quinoline-based drug candidates. Owing to their low binding energies with water, the clustering propensity of 8-substituted quinolinium ions was less than that of the 6- or 7-substituted analogues. We attribute these differences to the steric hinderance presented by subtituents in the 8-position. In addition, these experimental DMS results were complemented by extensive computational studies that determined cluster structures and relative thermodynamic stabilities.endifferential mobility spectrometryArticle