Details
| Original language | English |
|---|---|
| Pages (from-to) | 310-320 |
| Number of pages | 11 |
| Journal | Journal of the American Society for Mass Spectrometry |
| Volume | 37 |
| Issue number | 1 |
| Early online date | 15 Dec 2025 |
| Publication status | Published - 7 Jan 2026 |
Abstract
Field-induced ion activation in medium to high pressure regions of a mass spectrometer or ion mobility spectrometer can lead to changes in the ion structure, namely unfolding, tautomerization, or fragmentation. To either prevent mislabeling of spectra or utilize these effects efficiently, the underlying ion dynamics need to be understood. Hydroxyl-containing compounds in particular show significant fragmentation (loss of H2O), yet the energetics and mechanisms are not well studied. This is particularly true for primary hydroxyl groups, as the presumably formed primary carbocations are highly instable. In this study, we investigate the dynamics of the field-induced fragmentation of protonated primary and secondary alcohols using a combined theoretical and experimental approach. Specifically, we combine density functional theory and reaction kinetics modeling with fragmentation measurements using a HiKE-IMS-MS and tandem IMS device. We find that the fragmentation mechanism of both primary and secondary protonated alcohols proceeds via a protonated cyclopropane (PCP+) moiety. Especially for primary alcohols, this moiety enables an intramolecular SN2 reaction where the neutral H2O at the terminal carbon is substituted by an H-shift, directly yielding a secondary carbocation. Our results suggest quite high fragmentation rates, even at moderate ion activations, rendering protonated alcohols very unstable. However, we also find that neutral background water can form ion–solvent clusters with the protonated alcohols that effectively prevent the fragmentation. This could also help stabilize other labile ions in the future.
Keywords
- Density Functional Theory, Ion Fragmentation Mechanism, Ion Heating, Ion Mobility, Transition State Theory
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Structural Biology
- Chemistry(all)
- Spectroscopy
Cite this
- Standard
- Harvard
- Apa
- Vancouver
- BibTeX
- RIS
In: Journal of the American Society for Mass Spectrometry, Vol. 37, No. 1, 07.01.2026, p. 310-320.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Exploring Field-Induced Fragmentation of Protonated Alcohols
T2 - Mechanistic Insights and Stabilizing Ion–Solvent Clusters
AU - Timmermann, Philip
AU - G C Paudel, Anjita
AU - Eiceman, Gary
AU - Zimmermann, Stefan
AU - Haack, Alexander
N1 - Publisher Copyright: © 2025 The Authors. Published by American Chemical Society
PY - 2026/1/7
Y1 - 2026/1/7
N2 - Field-induced ion activation in medium to high pressure regions of a mass spectrometer or ion mobility spectrometer can lead to changes in the ion structure, namely unfolding, tautomerization, or fragmentation. To either prevent mislabeling of spectra or utilize these effects efficiently, the underlying ion dynamics need to be understood. Hydroxyl-containing compounds in particular show significant fragmentation (loss of H2O), yet the energetics and mechanisms are not well studied. This is particularly true for primary hydroxyl groups, as the presumably formed primary carbocations are highly instable. In this study, we investigate the dynamics of the field-induced fragmentation of protonated primary and secondary alcohols using a combined theoretical and experimental approach. Specifically, we combine density functional theory and reaction kinetics modeling with fragmentation measurements using a HiKE-IMS-MS and tandem IMS device. We find that the fragmentation mechanism of both primary and secondary protonated alcohols proceeds via a protonated cyclopropane (PCP+) moiety. Especially for primary alcohols, this moiety enables an intramolecular SN2 reaction where the neutral H2O at the terminal carbon is substituted by an H-shift, directly yielding a secondary carbocation. Our results suggest quite high fragmentation rates, even at moderate ion activations, rendering protonated alcohols very unstable. However, we also find that neutral background water can form ion–solvent clusters with the protonated alcohols that effectively prevent the fragmentation. This could also help stabilize other labile ions in the future.
AB - Field-induced ion activation in medium to high pressure regions of a mass spectrometer or ion mobility spectrometer can lead to changes in the ion structure, namely unfolding, tautomerization, or fragmentation. To either prevent mislabeling of spectra or utilize these effects efficiently, the underlying ion dynamics need to be understood. Hydroxyl-containing compounds in particular show significant fragmentation (loss of H2O), yet the energetics and mechanisms are not well studied. This is particularly true for primary hydroxyl groups, as the presumably formed primary carbocations are highly instable. In this study, we investigate the dynamics of the field-induced fragmentation of protonated primary and secondary alcohols using a combined theoretical and experimental approach. Specifically, we combine density functional theory and reaction kinetics modeling with fragmentation measurements using a HiKE-IMS-MS and tandem IMS device. We find that the fragmentation mechanism of both primary and secondary protonated alcohols proceeds via a protonated cyclopropane (PCP+) moiety. Especially for primary alcohols, this moiety enables an intramolecular SN2 reaction where the neutral H2O at the terminal carbon is substituted by an H-shift, directly yielding a secondary carbocation. Our results suggest quite high fragmentation rates, even at moderate ion activations, rendering protonated alcohols very unstable. However, we also find that neutral background water can form ion–solvent clusters with the protonated alcohols that effectively prevent the fragmentation. This could also help stabilize other labile ions in the future.
KW - Density Functional Theory
KW - Ion Fragmentation Mechanism
KW - Ion Heating
KW - Ion Mobility
KW - Transition State Theory
UR - http://www.scopus.com/inward/record.url?scp=105026665817&partnerID=8YFLogxK
U2 - 10.1021/jasms.5c00348
DO - 10.1021/jasms.5c00348
M3 - Article
C2 - 41397696
AN - SCOPUS:105026665817
VL - 37
SP - 310
EP - 320
JO - Journal of the American Society for Mass Spectrometry
JF - Journal of the American Society for Mass Spectrometry
SN - 1044-0305
IS - 1
ER -