skip to main content

Title: Field induced fragmentation spectra from reactive stage-tandem differential mobility spectrometry
A planar tandem differential mobility spectrometer was integrated with a middle reactive stage to fragment ions which were mobility selected in a first analyzer stage using characteristic compensation and separation fields. Fragmentation occurred in air at ambient pressure of 660 Torr (8.8 kPa) with electric fields of 10 to 35 kV cm −1 (E/N of 52 to 180 Td) between two 1 mm wide metal strips, located on each analyzer plate between the first and second mobility stages. Field induced fragmentation (FIF) spectra were produced by characterizing, in a last stage, the mobilities of fragment ions from protonated monomers of 43 oxygen-containing volatile organic compounds from five chemical classes. The extent of fragmentation was proportional to E/N with alcohols, aldehydes, and ethers undergoing multiples steps of fragmentation; acetates fragmented only to a single ion, protonated acetic acid. In contrast, fragmentation of ketones occurred only for methyl i-butyl ketone and 2-hexanone. Fragment ion identities were supported by mass-analysis and known fragmentation routes and suggested that field induced fragmentation at ambient pressure can introduce structural information into FIF spectra, establishing a foundation for chemical identification using mobility methods.
; ; ;
Award ID(s):
Publication Date:
Journal Name:
The Analyst
Page Range or eLocation-ID:
5314 to 5324
Sponsoring Org:
National Science Foundation
More Like this
  1. The valence photoionization of light and deuterated methanol dimers was studied by imaging photoelectron photoion coincidence spectroscopy in the 10.00–10.35 eV photon energy range. Methanol clusters were generated in a rich methanol beam in nitrogen after expansion into vacuum. They generally photoionize dissociatively to protonated methanol cluster cations, (CH 3 OH) n H + . However, the stable dimer parent ion (CH 3 OH) 2 + is readily detected below the dissociation threshold to yield the dominant CH 3 OH 2 + fragment ion. In addition to protonated methanol, we could also detect the water- and methyl-loss fragment ions of the methanol dimer cation for the first time. These newly revealed fragmentation channels are slow and cannot compete with protonated methanol cation formation at higher internal energies. In fact, the water- and methyl-loss fragment ions appear together and disappear at a ca. 150 meV higher energy in the breakdown diagram. Experiments with selectively deuterated methanol samples showed H scrambling involving two hydroxyl and one methyl hydrogens prior to protonated methanol formation. These insights guided the potential energy surface exploration to rationalize the dissociative photoionization mechanism. The potential energy surface was further validated by a statistical model including isotope effects tomore »fit the experiment for the light and the perdeuterated methanol dimers simultaneously. The (CH 3 OH) 2 + parent ion dissociates via five parallel channels at low internal energies. The loss of both CH 2 OH and CH 3 O neutral fragments leads to protonated methanol. However, the latter, direct dissociation channel is energetically forbidden at low energies. Instead, an isomerization transition state is followed by proton transfer from a methyl group, which leads to the CH 3 (H)OH + ⋯CH 2 OH ion, the precursor to the CH 2 OH-, H 2 O-, and CH 3 -loss fragments after further isomerization steps, in part by a roaming mechanism. Water loss yields the ethanol cation, and two paths are proposed to account for m/z 49 fragment ions after CH 3 loss. The roaming pathways are quickly outcompeted by hydrogen bond breaking to yield CH 3 OH 2 + , which explains the dominance of the protonated methanol fragment ion in the mass spectrum.« less
  2. We investigated the collision-induced dissociation (CID) reactions of a protonated Hoogsteen 9-methylguanine–1-methylcytosine base pair (HG-[9MG·1MC + H] + ), which aims to address the mystery of the literature reported “anomaly” in product ion distributions and compare the kinetics of a Hoogsteen base pair with its Watson-Crick isomer WC-[9MG·1MC + H] + (reported recently by Sun et al. ; Phys. Chem. Chem. Phys. , 2020, 22 , 24986). Product ion cross sections and branching ratios were measured as a function of center-of-mass collision energy using guided-ion beam tandem mass spectrometry, from which base-pair dissociation energies were determined. Product structures and energetics were assessed using various theories, of which the composite DLPNO-CCSD(T)/aug-cc-pVTZ//ωB97XD/6-311++G(d,p) was adopted as the best-performing method for constructing a reaction potential energy surface. The statistical Rice–Ramsperger–Kassel–Marcus theory was found to provide a useful framework for rationalizing the dominating abundance of [1MC + H] + over [9MG + H] + in the fragment ions of HG-[9MG·1MC + H] + . The kinetics analysis proved the necessity for incorporating into kinetics modeling not only the static properties of reaction minima and transition states but more importantly, the kinetics of individual base-pair conformers that have formed in collisional activation. The analysis also pinpointedmore »the origin of the statistical kinetics of HG-[9MG·1MC + H] + vs. the non-statistical behavior of WC-[9MG·1MC + H] + in terms of their distinctively different intra-base-pair hydrogen-bonds and consequently the absence of proton transfer between the N1 position of 9MG and the N3′ of 1MC in the Hoogsteen base pair. Finally, the Hoogsteen base pair was examined in the presence of a water ligand, i.e. , HG-[9MG·1MC + H] + ·H 2 O. Besides the same type of base-pair dissociation as detected in dry HG-[9MG·1MC + H] + , secondary methanol elimination was observed via the S N 2 reaction of water with nucleobase methyl groups.« less
  3. Decavanadate (V 10 O 28 6− or V10) is a paradigmatic member of the polyoxidometalate (POM) family, which has been attracting much attention within both materials/inorganic and biomedical communities due to its unique structural and electrochemical properties. In this work we explored the utility of high-resolution electrospray ionization (ESI) mass spectrometry (MS) and ion exclusion chromatography LC/MS for structural analysis of V10 species in aqueous solutions. While ESI generates abundant molecular ions representing the intact V10 species, their isotopic distributions show significant deviations from the theoretical ones. A combination of high-resolution MS measurements and hydrogen/deuterium exchange allows these deviations to be investigated and interpreted as a result of partial reduction of V10. While the redox processes are known to occur in the ESI interface and influence the oxidation state of redox-active analytes, the LC/MS measurements using ion exclusion chromatography provide unequivocal evidence that the mixed-valence V10 species exist in solution, as extracted ion chromatograms representing V10 molecular ions at different oxidation states exhibit distinct elution profiles. The spontaneous reduction of V10 in solution is seen even in the presence of hydrogen peroxide and has not been previously observed. The susceptibility to reduction of V10 is likely to be shared bymore »other redox active POMs. In addition to the molecular V10 ions, a high-abundance ionic signal for a V 10 O 26 2− anion was displayed in the negative-ion ESI mass spectra. None of the V 10 O 26 cations were detected in ESI MS, and only a low-abundance signal was observed for V 10 O 26 anions with a single negative charge, indicating that the presence of abundant V 10 O 26 2− anions in ESI MS reflects gas-phase instability of V 10 O 28 anions carrying two charges. The gas-phase origin of the V 10 O 26 2− anion was confirmed in tandem MS measurements, where mild collisional activation was applied to V10 molecular ions with an even number of hydrogen atoms (H 4 V 10 O 28 2− ), resulting in a facile loss of H 2 O molecules and giving rise to V 10 O 26 2− as the lowest-mass fragment ion. Water loss was also observed for V 10 O 28 anions carrying an odd number of hydrogen atoms ( e.g. , H 5 V 10 O 28 − ), followed by a less efficient and incomplete removal of an OH˙ radical, giving rise to both HV 10 O 26 − and V 10 O 25 − fragment ions. Importantly, at least one hydrogen atom was required for ion fragmentation in the gas phase, as no further dissociation was observed for any hydrogen-free V10 ionic species. The presented workflow allows a distinction to be readily made between the spectral features revealing the presence of non-canonical POM species in the bulk solution from those that arise due to physical and chemical processes occurring in the ESI interface and/or the gas phase.« less
  4. Ion dissociation is the usual basis for tandem MS analysis but a significant limitation is that only charged fragments from ion dissociation events are detected while neutral fragments are simply lost. This study reports our continued effort to solve this problem by developing atmospheric pressure neutral reionization mass spectrometry (APNR). In APNR, analyte ions are thermally dissociated (atmospheric pressure thermal dissociation, APTD) followed by soft reionization using electrosonic spray ionization (ESSI). Our results show that APNR is a powerful method for structural analysis of various biomolecules such as peptides, saccharides and nucleotides, as well as for elucidating unimolecular ion dissociation mechanisms. It was found that APNR provides extensive fragment ions including a series of y ions in peptides, which benefit sequencing and provide complementary information to collision induced dissociation (CID). In particular, direct cleavage of disulfide bonds of peptides occurs during APTD, facilitating peptide sequencing and disulfide bond mapping. In addition, many cross-ring cleavage fragments are detected during APNR analysis of oligosaccharides, indicating that the APTD dissociation process is energetic and potentially useful for identifying glycan linkage sites. Fragmentation patterns of oligosaccharide isomers can be used for their differentiation. Furthermore, in the cases of dissociation of nucleotides and synthetic naphthoylindolemore »drugs, the putative neutral, phosphorylated riboses and indoles, were successfully detected using APNR, providing strong evidence to confirm previously proposed unimolecular ion dissociation mechanisms. We believe this APNR technique along with APTD should be of high value in structure determination of biomolecules.« less
  5. Recent studies have illuminated connections between spontaneous chemical reactions that cause isomerization at specific protein residues and various age-related diseases including cataracts and Alzheimer's. These discoveries provide impetus for better analytical methods to detect and characterize isomerization in proteins, which will enable a more complete understanding of the underlying relationship between these modifications and biology. Herein we employ a two-dimensional approach for identification of peptides isomers that also includes pinpointing of the modified residue. Collision-induced dissociation is used to fragment ions in the first dimension, followed by separation of the fragments with travelling-wave ion mobility. By comparing data obtained from both isomers, differences in either fragment-ion intensities or arrival-time distributions can be used to identify isomeric forms and the specific site of modification within the peptides. Synthetic peptide standards with sequences derived from long-lived proteins in the eye lens and isomerization at serine, aspartic acid, and glutamic acid were examined. Although both dimensions are capable of isomer identification, ion mobility is much better at determining the site of modification. In general, separation of isomeric forms by ion mobility is possible but does not follow predictable trends dictated by sequence or fragment-ion length. In most cases, however, the site of isomerizationmore »can be precisely determined.« less