Measurement and Theory of Gas-Phase Ion Mobility Shifts Resulting from Isotopomer Mass Distribution Changes

Abstract

The unanticipated discovery of recent ultra-high-resolution ion mobility spectrometry (IMS) measurements revealing that isotopomers compounds that differ only in the isotopic substitution sitescan be separated has raised questions as to the physical basis for their separation. A study comparing IMS separations for two isotopomer sets in conjunction with theory and simulations accounting for ion rotational effects provides the first-ever prediction of rotation-mediated shifts. The simulations produce observable mobility shifts due to differences in gas−ion collision frequency and translational-to-rotational energy transfer. These differences can be attributed to distinct changes in the moment of inertia and center of mass between isotopomers. The simulations are in broad agreement with the observed experiments and consistent with relative mobility differences between isotopomers. These results provide a basis for refining IMS theory and a new foundation to obtain additional structural insights through IMS.

Isomer and Conformer-Specific Mass Distribution-Based Isotopic Shifts in High-Resolution Cyclic Ion Mobility Separations

“…21,34 In addition to these experimental measurements, computational modeling in IMoS 2.0 also validated that mass distribution-based effects were the cause for the observed isotopomer separations. 34 While there have been fewer demonstrations of isotopologue and isotopomer separations with TWIMS, it is important to discuss contributions from groups utilizing other IMS-based techniques, such as field asymmetric ion mobility spectrometry. Additionally, it is necessary to mention that atmospheric pressure DTIMS has also been utilized to separate isotopologues of small molecules (e.g., acetone and benzenelike compounds).…”

“…SLIM IMS-MS demonstrated that various tandem mass tag (TMT) isotopomers were resolved after >1 km of separation. 21,34 From these studies, it was hypothesized that mass distribution-based effects (i.e., contributions from both changes in the center of mass and moments of inertia) were the basis for the isotopomer separations. 21,34 In addition to these experimental measurements, computational modeling in IMoS 2.0 also validated that mass distribution-based effects were the cause for the observed isotopomer separations.…”

“…21,34 From these studies, it was hypothesized that mass distribution-based effects (i.e., contributions from both changes in the center of mass and moments of inertia) were the basis for the isotopomer separations. 21,34 In addition to these experimental measurements, computational modeling in IMoS 2.0 also validated that mass distribution-based effects were the cause for the observed isotopomer separations. 34 While there have been fewer demonstrations of isotopologue and isotopomer separations with TWIMS, it is important to discuss contributions from groups utilizing other IMS-based techniques, such as field asymmetric ion mobility spectrometry.…”

Experimental Measurements of Relative Mobility Shifts Resulting from Isotopic Substitutions with High-Resolution Cyclic Ion Mobility Separations

“…Specifically, FAIMS-based methods have separated amino acid and peptide isotopomers, 33,36 while SLIM IMS-based separations have resolved TMT ones. 25,37 Although the separation mechanism in FAIMS remains unclear, in the SLIM IMS isotopomer separations, it was hypothesized that shifts in mass distribution (i.e., contributions from changes in the center of mass and moments of inertia) were the basis for their mobility differences. 25,37 These exciting results potentially imply that the scientific community should redefine IMS theory to include additional mass distribution-based terms.…”

Evaluating the Utility of Temporal Compression in High-Resolution Traveling Wave-Based Cyclic Ion Mobility Separations

“…Since IMS resolution scales approximately by the square root of the separation pathlength (e.g., a 100 m separation would provide 10 times higher resolution than a 1 m separation), longer IMS separations are very attractive for resolving very structurally similar molecules, such as cis/trans lipid isomers, peptide epimers, oligosaccharide anomers, and isotopologues/isotopomers. ,− These longer pathlength implementations are made possible by the lower voltage requirements in TWIMS and not possible in other IMS modalities, such as the large voltage drop required in DTIMS to achieve even a few meters of separation. − Currently, two commercially available traveling wave-based IMS-MS platforms (structures for lossless ion manipulations, MOBIE, from MOBILion, and the Select Series Cyclic IMS, cIMS, from Waters Corporation) have exploited this and achieved separation pathlengths >10 m and up to 2 km in a homebuilt platform. , Both SLIM IMS-MS and cIMS-MS utilize traveling wave separations, giving added flexibility and customization for experiments (e.g., IMS/IMS, peak selection, etc. ).…”