Using differential mobility spectrometry to measure ion solvation: an examination of the roles of solvents and ionic structures in separating quinoline-based drugs

Abstract

Understanding 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.

Analyzing Glycopeptide Isomers by Combining Differential Mobility Spectrometry with Electron- and Collision-Based Tandem Mass Spectrometry

“…How could these sites of protonation influence the DMS separation (or lack thereof) for the glycopeptides studied here? For the case of the separated doubly protonated species, the more negative CV shift by the MUC5AC-13 isomer suggests that it binds more strongly with the acetonitrile vapor added to the DMS cell than does the MUC5AC-3 isomer [34][35][36]. When considering the structural variation between isomers that could cause such a CV shift, the presence of possible intramolecular hydrogen bonds (IMHBs) in the MUC5AC-3 isomer that internally solvate a site of protonation could be proposed (vide infra).…”

Recommendations for reporting ion mobility Mass Spectrometry measurements

“…The development of FAIMS science since the introduction of these ion types in early work by Guevremont has brought forward a deeper understanding and re‐evaluation of these definitions in several aspects. First, all “ion types” are actually “ion‐gas pair” types—the same ions can assume different types in different gases based upon the ion/molecule interactions between these species (Barnett et al, ; Levin et al, ; Campbell, Zhu, & Hopkins, ; Liu et al, ; Liu et al, ). Generally, increasing the mass and polarizability of gas molecules shifts ions from type C to B to A.…”

Fine adjustment of gas modifier loadings for separation of epimeric glycopeptides using differential ion mobility spectrometry mass spectrometry

“…Many studies have been carried out to examine the fundamental aspects of ion separation under DMS conditions. [20][21][22][23][24] The effects of the gas modifier and other experimental conditions on the compensation voltage (CoV) of different analyte ions have been extensively studied. 25,26 The CoV shift of the analyte ions has been shown to correlate well with the square root of the inverse of the reduced mass of the "modifierclustered" analyte ions 27 and the Gibbs free energy for the cluster formation.…”

“…25,26 The CoV shift of the analyte ions has been shown to correlate well with the square root of the inverse of the reduced mass of the "modifierclustered" analyte ions 27 and the Gibbs free energy for the cluster formation. 23,28 The amino acid sequence of the peptide used in this study was derived from one of the tryptic digested fragments of the Arginine Deiminase (ARD) protein and was modified with galactose (Gal), glucose (Glc) and mannose (Man) at the threonine residue to give EIDYIT (Gal)PAR, EIDYIT (Glc)PAR and EIDYIT (Man)PAR, respectively. These glycopeptides were custom-synthesized commercially (RoYo Biotech Co., Ltd, Shanghai, China) and were used without further purification.…”