Hybrid 213 nm photodissociation of cationized Sterol lipid ions yield [M]+. Radical products for improved structural characterization using multistage tandem mass spectrometry

West, Henry; Reid, Gavin E.

doi:10.1016/j.aca.2020.10.013

Cited by 25 publications

(23 citation statements)

References 40 publications

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“…In two recent studies, the commercially available 213 nm UVPD unit for the Orbitrap Fusion Lumos Tribrid (Thermo Fisher Scientific) was used to study organic micro-pollutants (OMPs) and steroids. In particular, West and Reid utilized the multistage tandem MS capabilities of the instrument to generate radical cations from sodiated steroids via 213 nm UVPD and subsequently activate radical ions via vendor-specific CID (higher-collisional dissociation; HCD) [68]. Corresponding MS n tandem mass spectra for isomeric species 4β-OH cholesterol, 7α-OH cholesterol, and 25-OH cholesterol are shown in Fig.…”

Section: Photon-based Fragmentationmentioning

confidence: 99%

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Advanced tandem mass spectrometry in metabolomics and lipidomics—methods and applications

Heiles

2021

Anal Bioanal Chem

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Metabolomics and lipidomics are new drivers of the omics era as molecular signatures and selected analytes allow phenotypic characterization and serve as biomarkers, respectively. The growing capabilities of untargeted and targeted workflows, which primarily rely on mass spectrometric platforms, enable extensive charting or identification of bioactive metabolites and lipids. Structural annotation of these compounds is key in order to link specific molecular entities to defined biochemical functions or phenotypes. Tandem mass spectrometry (MS), first and foremost collision-induced dissociation (CID), is the method of choice to unveil structural details of metabolites and lipids. But CID fragment ions are often not sufficient to fully characterize analytes. Therefore, recent years have seen a surge in alternative tandem MS methodologies that aim to offer full structural characterization of metabolites and lipids. In this article, principles, capabilities, drawbacks, and first applications of these “advanced tandem mass spectrometry” strategies will be critically reviewed. This includes tandem MS methods that are based on electrons, photons, and ion/molecule, as well as ion/ion reactions, combining tandem MS with concepts from optical spectroscopy and making use of derivatization strategies. In the final sections of this review, the first applications of these methodologies in combination with liquid chromatography or mass spectrometry imaging are highlighted and future perspectives for research in metabolomics and lipidomics are discussed. Graphical abstract

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Section: Photon-based Fragmentationmentioning

confidence: 99%

“…Fig.3A, C MS3 and B MS 4 of sodiated A 4β-OH cholesterol, B 7a-OH cholesterol, and C 25-OH cholesterol employing 213 nm UVPD followed by HCD allow to distinguish steroid isomers. Reprinted with permission from[68], copyright 2020 Elsevier B.V.…”

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confidence: 99%

Advanced tandem mass spectrometry in metabolomics and lipidomics—methods and applications

Heiles

2021

Anal Bioanal Chem

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“…We also used the extensive tabulated data for rat (adult, male Wistar) sciatic nerve lipids that were analyzed by imaging MS [32]. In our current study, the conditions we used for analyzing the lipids were not sufficient to detect cholesterol, a major myelin constituent, which is usually cationized via alkaline hydrolysis and detected, for example, as ammoniated, lithiated, or sodiated adducts [33]. Spectral accuracy of our original data was determined using MassWorks (Version 6,0,0,0) software from Cerno Bioscience (LasVegas, NV 89144) [34,35].…”

Section: Lipid Analysis By Mass Spectrometrymentioning

confidence: 99%

Metabolically-Incorporated Deuterium in Myelin Localized by Neutron Diffraction and Identified by Mass Spectrometry

Baumann

Denninger

Domin

et al. 2021

Preprint

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Myelin is a natural and dynamic multilamellar membrane structure that continues to be of significant biological and neurological interest, especially its biosynthesis and assembly in the context of its normal formation and renewal, and pathological breakdown. To explore further the usefulness of neutron diffraction in the structural analysis of myelin, we investigated the use of in vivo labeling by metabolically incorporating via drinking water nontoxic levels of deuterium (2H; D) into pregnant dams and their developing embryos. All of the mice were sacrificed when the pups were about 60 days old. Myelinated nerves were dissected, fixed in glutaraldehyde and examined by neutron diffraction. Parallel samples that were unfixed were frozen for mass spectrometry (MS). Analysis of the neutron diffraction patterns of the sciatic nerves from deuterium-fed mice (D mice) versus the controls (H mice) showed no appreciable differences in myelin periodicity, but major differences in the intensities of the Bragg peaks. The neutron scattering density profiles showed an appreciable increase in density at the center of the membrane bilayer in the D mice, particularly in the pups. MS analysis of the lipids isolated from the trigeminal nerves demonstrated that the level of D was greater in the pups compared to their mother: 97.6% +/- 2.0% (n=54; range 89.6% to 99.6%) versus 60.6% +/- 26.4% (n=27; range 11.4% to 97.3%). Deuteration in the mother also varied by lipid species, and among lipid subspecies. Three molecular species of phosphatidylcholine (PC), phosphatidylinositol (PI), and diglycerol (DG) were the most deuterated lipids, and sulfatide (SHexCer), one species of sphingomyelin (SM), and triacylglycerol (TG) were the least deuterated. The distribution pattern of deuterium in the D pups was always bell-shaped, and the average number of D atoms ranged from a low of ~4 in fatty acid (FA), to a high of ~9 in cerebroside (HexCer). By contrast, in D dam only about one third of the lipids had symmetric bell-shaped distributions; most had more complex, overlapping distributions that were weighted toward a lower average number of D atom labels. The average number of D atoms ranged from a low of ~3 to 4 in FA and in one species of SHexCer, to a high of 6 to 7 in HexCer and SM. In D pups, the consistently high level of deuteration can be attributed to their de novo lipogenesis during gestation and continuation of rapid myelination postnatally. In D dam, the widely varying levels of deuteration of lipids likely depends on the relative metabolic stability of the particular lipid species during myelin maintenance in the mature animal. Our current findings demonstrate that stably-incorporated D label can be detected and localized using neutron diffraction in a complex tissue such as myelin; and moreover, that MS can be used to screen a broad range of deuterated lipid species to monitor differential rates of lipid turnover. In addition to helping to develop a comprehensive understanding of the de novo synthesis and turnover of specific lipids in normal and abnormal myelin, our results also suggest application to myelin proteins, as well as more broadly to the molecular constituents of other biological tissues.

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“…Thus, site-specific derivatization on C=C bonds, such as epoxidation [13][14][15][16], singlet oxygen ene reaction [17], and the Paternò-Büchi (PB) reaction [18,19], have been developed to enable double bond localization in conjunction with CID. Ultraviolet photodissociation (UVPD) as an alternative ion activation method has been utilized independently for providing detailed structural characterization of intact lipids [20][21][22]. UVPD MS/MS at 193 nm has previously been implemented in shotgun and HPLC workflows capable of assigning sn-positions of fatty acyls and resolving C=C positional isomers of glycerophospholipids (GPLs) [23,24] and sphingolipids [25].…”

Section: Introductionmentioning

confidence: 99%

Site-Specific Photochemical Reaction for Improved C=C Location Analysis of Unsaturated Lipids by Ultraviolet Photodissociation

Zhao

Cao

et al. 2022

Research

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Unraveling the complexity of the lipidome requires the development of novel approaches to facilitate structural identification and characterization of lipid species with isomer-level discrimination. Ultraviolet photodissociation tandem mass spectrometry (UVPD MS/MS) is a promising tool for structure determination of lipids. The sensitivity of UVPD for lipid analysis however is limited mainly due to weak absorption of UV photons by a C=C. Herein, a C=C site-specific derivatization, the Paternò-Büchi (PB) reaction, was used to incorporate a chromophore to the C=C moiety in fatty acyls, leading to significantly improved UVPD efficiency and sensitivity for pinpointing C=C locations. The wavelength-dependent photodissociation of the PB products demonstrated 4-CF3-benzophenone as the best reagent for UVPD in terms of the efficiency of generating C=C diagnostic fragments and simplicity for C=C location assignments. We demonstrated the effectiveness of this approach for the shotgun profiling of C=C location isomers in different lipid classes from complex lipid extracts, highlighting its potential to advancing the identification of the C=C bond locations in unsaturated lipids.

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Hybrid 213 nm photodissociation of cationized Sterol lipid ions yield [M]+. Radical products for improved structural characterization using multistage tandem mass spectrometry

Cited by 25 publications

References 40 publications

Advanced tandem mass spectrometry in metabolomics and lipidomics—methods and applications

Advanced tandem mass spectrometry in metabolomics and lipidomics—methods and applications

Metabolically-Incorporated Deuterium in Myelin Localized by Neutron Diffraction and Identified by Mass Spectrometry

Site-Specific Photochemical Reaction for Improved C=C Location Analysis of Unsaturated Lipids by Ultraviolet Photodissociation

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