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1. Structural characterization of fatty acid anions via gas‐phase charge inversion using Mg(tri‐butyl‐terpyridine) ₂ ²⁺ reagent ions

   https://doi.org/10.1002/rcm.9741  

   Nsiah, Sarah_T; Fabijanczuk, Kimberly_C; McLuckey, Scott_A (April 2024, Rapid Communications in Mass Spectrometry)

   RationaleFree fatty acids and lipid classes containing fatty acid esters are major components of lipidome. In the absence of a chemical derivatization step, FA anions do not yield all of the structural information that may be of interest under commonly used collision‐induced dissociation (CID) conditions. A line of work that avoids condensed‐phase derivatization takes advantage of gas‐phase ion/ion chemistry to charge invert FA anions to an ion type that provides the structural information of interest using conventional CID. This work was motivated by the potential for significant improvement in overall efficiency for obtaining FA chain structural information. MethodsA hybrid triple quadrupole/linear ion‐trap tandem mass spectrometer that has been modified to enable the execution of ion/ion reaction experiments was used to evaluate the use of 4,4′,4″‐tri‐tert‐butyl‐2,2′:6′,2″‐terpyridine (ttb‐Terpy) as the ligand in divalent magnesium complexes for charge inversion of FA anions. ResultsMg(ttb‐Terpy)₂²⁺complexes provide significantly improved efficiency in producing structurally informative products from FA ions relative to Mg(Terpy)₂²⁺complexes, as demonstrated for straight‐chain FAs, branched‐chain FAs, unsaturated FAs, and cyclopropane‐containing FAs. It was discovered that most of the structurally informative fragmentation from [FA‐H + Mg(ttb‐Terpy)]⁺results from the loss of a methyl radical from the ligand followed by radical‐directed dissociation (RDD), which stands in contrast to the charge‐remote fragmentation (CRF) believed to be operative with the [FA‐H + Mg(Terpy)]⁺ions. ConclusionsThis work demonstrates that a large fraction of product ions from the CID of ions of the form [FA‐H + Mg(ttb‐Terpy)]⁺are derived from RDD of the FA backbone, with a very minor fraction arising from structurally uninformative dissociation channels. This ligand provides an alternative to previously used ligands for the structural characterization of FAs via CRF. 

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2. Atmospheric pressure neutral reionization mass spectrometry for structural analysis

   https://doi.org/10.1039/c7sc01999h  

   Liu, Pengyuan; Zhao, Pengyi; Cooks, R. Graham; Chen, Hao (January 2017, Chemical Science)

   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 naphthoylindole 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. 

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3. Charge transfer dissociation of a branched glycan with alkali and alkaline earth metal adducts

   https://doi.org/10.1002/jms.4774  

   Sasiene, Zachary_J; Ropartz, David; Rogniaux, Hélène; Jackson, Glen_P (June 2021, Journal of Mass Spectrometry)

   Abstract Alkali and alkaline earth metal adducts of a branched glycan, XXXG, were analyzed with helium charge transfer dissociation (He‐CTD) and low‐energy collision‐induced dissociation (LE‐CID) to investigate if metalation would impact the type of fragments generated and the structural characterization of the analyte. The studied adducts included 1+ and 2+ precursors involving one or more of the cations: H⁺, Na⁺, K⁺, Ca²⁺, and Mg²⁺. Regardless of the metal adduct, He‐CTD generated abundant and numerous glycosidic and cross‐ring cleavages that were structurally informative and able to identify the 1,4‐linkage and 1,6‐branching patterns. In contrast, the LE‐CID spectra mainly contained glycosidic cleavages, consecutive fragments, and numerous neutral losses, which complicated spectral interpretation. LE‐CID of [M + K + H]²⁺and [M + Na]⁺precursors generated a few cross‐ring cleavages, but they were not sufficient to identify the 1,4‐linkage and 1,6‐branching pattern of the XXXG xyloglucan. He‐CTD predominantly generated 1+ fragments from 1+ precursors and 2+ product ions from 2+ precursors, although both LE‐CID and He‐CTD were able to generate 1+ product ions from 2+ adducts of magnesium and calcium. The singly charged fragments derive from the loss of H⁺from the metalated product ions and the formation of a protonated complementary product ion; such observations are similar to previous reports for magnesium and calcium salts undergoing electron capture dissociation (ECD) activation. However, during He‐CTD, the [M + Mg]²⁺precursor generated more singly charged product ions than [M + Ca]²⁺, either because Mg has a higher second ionization potential than Ca or because of conformational differences and the locations of the charging adducts during fragmentation. He‐CTD of the [M + 2Na]²⁺and the [M + 2 K]²⁺precursors generated singly charged product ions from the loss of a sodium ion and potassium ion, respectively. In summary, although the metal ions influence the mass and charge state of the observed product ions, the metal ions had a negligible effect on the types of cross‐ring cleavages observed. 

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4. Decoding the Fucose Migration Product during Mass‐Spectrometric analysis of Blood Group Epitopes

   https://doi.org/10.1002/anie.202302883  

   Lettow, Maike; Greis, Kim; Mucha, Eike; Lambeth, Tyler R.; Yaman, Murat; Kontodimas, Vasilis; Manz, Christian; Hoffmann, Waldemar; Meijer, Gerard; Julian, Ryan R.; et al (May 2023, Angewandte Chemie International Edition)

   Abstract Fucose is a signaling carbohydrate that is attached at the end of glycan processing. It is involved in a range of processes, such as the selectin‐dependent leukocyte adhesion or pathogen‐receptor interactions. Mass‐spectrometric techniques, which are commonly used to determine the structure of glycans, frequently show fucose‐containing chimeric fragments that obfuscate the analysis. The rearrangement leading to these fragments—often referred to as fucose migration—has been known for more than 25 years, but the chemical identity of the rearrangement product remains unclear. In this work, we combine ion‐mobility spectrometry, radical‐directed dissociation mass spectrometry, cryogenic IR spectroscopy of ions, and density‐functional theory calculations to deduce the product of the rearrangement in the model trisaccharides Lewis x and blood group H2. The structural search yields the fucose moiety attached to the galactose with anα(1→6) glycosidic bond as the most likely product. 

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5. Mass spectrometry and computational study of collision-induced dissociation of 9-methylguanine–1-methylcytosine base-pair radical cation: intra-base-pair proton transfer and hydrogen transfer, non-statistical dissociation, and reaction with a water ligand

   https://doi.org/10.1039/d0cp01788d  

   Sun, Yan; Moe, May Myat; Liu, Jianbo (July 2020, Physical Chemistry Chemical Physics)

   null (Ed.)

   A combined experimental and theoretical study is presented on the collision-induced dissociation (CID) of 9-methylguanine–1-methylcytosine base-pair radical cation (abbreviated as [9MG·1MC]˙ + ) and its monohydrate ([9MG·1MC]˙ + ·H 2 O) with Xe and Ar gases. Product ion mass spectra were measured as a function of collision energy using guided-ion beam tandem mass spectrometry, from which cross sections and threshold energies for various dissociation pathways were determined. Electronic structure calculations were performed at the DFT, RI-MP2 and DLPNO-CCSD(T) levels of theory to identify product structures and map out reaction potential energy surfaces. [9MG·1MC]˙ + has two structures: a conventional structure 9MG˙ + ·1MC (population 87%) consisting of hydrogen-bonded 9-methylguanine radical cation and neutral 1-methylcytosine, and a proton-transferred structure [9MG − H]˙·[1MC + H] + (less stable, population 13%) formed by intra-base-pair proton transfer from the N1 of 9MG˙ + to the N3 of 1MC within 9MG˙ + ·1MC. The two structures have similar dissociation energies but can be distinguished in that 9MG˙ + ·1MC dissociates into 9MG˙ + and 1MC whereas [9MG – H]˙·[1MC + H] + dissociates into neutral [9MG – H]˙ radical and protonated [1MC + H] + . An intriguing finding is that, in both Xe- and Ar-induced CID of [9MG·1MC]˙ + , product ions were overwhelmingly dominated by [1MC + H] + , which is contrary to product distributions predicted using a statistical reaction model. Monohydration of [9MG·1MC]˙ + reversed the populations of the conventional structure (43%) vs. the proton-transferred structure (57%) and induced new reactions upon collisional activation, of which intra-base-pair hydrogen transfer produced [9MG + H] + and the reaction of the water ligand with a methyl group in [9MG·1MC]˙ + led to methanol elimination from [9MG·1MC]˙ + ·H 2 O. 

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