Characterization of Glycerophospholipids at Multiple Isomer Levels Mn(II)-catalyzed Epoxidation

Overview

Journal Analyst

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2022 Sep 21

PMID 36128870

Authors

Xi Chen

Shuli Tang

Dallas Freitas

Erin Hirtzel

Heyong Cheng

Xin Yan

Affiliations

Soon will be listed here.

Abstract

Characterization of glycerophospholipid isomers is of significant importance as they play different roles in physiological and pathological processes. In this work, we present a novel and bifunctional derivatization method utilizing Mn(II)-catalyzed epoxidation to simultaneously identify carbon-carbon double bond (CC bond)- and stereonumbering ()-positional isomers of phosphatidylcholine. Mn(II) coordinates with picolinic acid and catalyzes epoxidation of unsaturated lipids by peracetic acid. Collision-induced dissociation (CID) of the epoxides generates diagnostic ions that can be used to locate CC bond positions. Meanwhile, CID of Mn(II) ion-lipid complexes produces characteristic ions for determination of positions. This bifunctional derivatization takes place in seconds, and the diagnostic ions produced in CID are clear and easy to interpret. Moreover, relative quantification of CC bond-and -positional isomers was achieved. The capability of this method in identifying lipids at multiple isomer levels was shown using lipid standards and lipid extracts from complex biological samples.

Citing Articles

Dual Metal Electrolysis in Theta Capillary for Lipid Analysis.

Sengupta A, Edwards M, Yan X Int J Mass Spectrom. 2024; 494.

PMID: 38911479 PMC: 11192522. DOI: 10.1016/j.ijms.2023.117137.

Lipid Isobaric Mass Tagging for Enhanced Relative Quantification of Unsaturated -Positional Isomers.

Yang T, Tang S, Feng J, Yan X ACS Meas Sci Au. 2024; 4(2):213-222.

PMID: 38645577 PMC: 11027206. DOI: 10.1021/acsmeasuresciau.3c00062.

In situ droplet-based on-tissue chemical derivatization for lipid isomer characterization using LESA.

Freitas D, Chen X, Hirtzel E, Edwards M, Kim J, Wang H Anal Bioanal Chem. 2023; 415(18):4197-4208.

PMID: 37017722 PMC: 10392465. DOI: 10.1007/s00216-023-04653-3.

References

Williams P, Klein D, Greer S, Brodbelt J . Pinpointing Double Bond and sn-Positions in Glycerophospholipids via Hybrid 193 nm Ultraviolet Photodissociation (UVPD) Mass Spectrometry. J Am Chem Soc. 2017; 139(44):15681-15690. PMC: 5760168. DOI: 10.1021/jacs.7b06416. View

Thomas M, Mitchell T, Harman D, Deeley J, Nealon J, Blanksby S . Ozone-induced dissociation: elucidation of double bond position within mass-selected lipid ions. Anal Chem. 2007; 80(1):303-11. DOI: 10.1021/ac7017684. View

Hancock S, Poad B, Batarseh A, Abbott S, Mitchell T . Advances and unresolved challenges in the structural characterization of isomeric lipids. Anal Biochem. 2016; 524:45-55. DOI: 10.1016/j.ab.2016.09.014. View

Zhao X, Zhang W, Zhang D, Liu X, Cao W, Chen Q . A lipidomic workflow capable of resolving - and C[double bond, length as m-dash]C location isomers of phosphatidylcholines. Chem Sci. 2020; 10(46):10740-10748. PMC: 7020929. DOI: 10.1039/c9sc03521d. View

Feider C, Macias L, Brodbelt J, Eberlin L . Double Bond Characterization of Free Fatty Acids Directly from Biological Tissues by Ultraviolet Photodissociation. Anal Chem. 2020; 92(12):8386-8395. PMC: 7433749. DOI: 10.1021/acs.analchem.0c00970. View

Cao W, Ma X, Li Z, Zhou X, Ouyang Z . Locating Carbon-Carbon Double Bonds in Unsaturated Phospholipids by Epoxidation Reaction and Tandem Mass Spectrometry. Anal Chem. 2018; 90(17):10286-10292. DOI: 10.1021/acs.analchem.8b02021. View

Unsihuay D, Su P, Hu H, Qiu J, Kuang S, Li Y . Imaging and Analysis of Isomeric Unsaturated Lipids through Online Photochemical Derivatization of Carbon-Carbon Double Bonds*. Angew Chem Int Ed Engl. 2021; 60(14):7559-7563. PMC: 8815435. DOI: 10.1002/anie.202016734. View

Yoo H, Hakansson K . Determination of double bond location in fatty acids by manganese adduction and electron induced dissociation. Anal Chem. 2010; 82(16):6940-6. DOI: 10.1021/ac101217x. View

Thomas M, Mitchell T, Harman D, Deeley J, Murphy R, Blanksby S . Elucidation of double bond position in unsaturated lipids by ozone electrospray ionization mass spectrometry. Anal Chem. 2007; 79(13):5013-22. PMC: 3083263. DOI: 10.1021/ac0702185. View

10.

Pechlaner R, Kiechl S, Mayr M . Potential and Caveats of Lipidomics for Cardiovascular Disease. Circulation. 2016; 134(21):1651-1654. DOI: 10.1161/CIRCULATIONAHA.116.025092. View

11.

Feng G, Gao M, Wang L, Chen J, Hou M, Wan Q . Dual-resolving of positional and geometric isomers of C=C bonds via bifunctional photocycloaddition-photoisomerization reaction system. Nat Commun. 2022; 13(1):2652. PMC: 9098869. DOI: 10.1038/s41467-022-30249-z. View

12.

Poad B, Zheng X, Mitchell T, Smith R, Baker E, Blanksby S . Online Ozonolysis Combined with Ion Mobility-Mass Spectrometry Provides a New Platform for Lipid Isomer Analyses. Anal Chem. 2017; 90(2):1292-1300. PMC: 5771865. DOI: 10.1021/acs.analchem.7b04091. View

13.

Becher S, Esch P, Heiles S . Relative Quantification of Phosphatidylcholine sn-Isomers Using Positive Doubly Charged Lipid-Metal Ion Complexes. Anal Chem. 2018; 90(19):11486-11494. DOI: 10.1021/acs.analchem.8b02731. View

14.

Thomas M, Mitchell T, Blanksby S . Ozonolysis of phospholipid double bonds during electrospray ionization: a new tool for structure determination. J Am Chem Soc. 2006; 128(1):58-9. DOI: 10.1021/ja056797h. View

15.

Lu H, Zhang H, Xu S, Li L . Review of Recent Advances in Lipid Analysis of Biological Samples via Ambient Ionization Mass Spectrometry. Metabolites. 2021; 11(11). PMC: 8623600. DOI: 10.3390/metabo11110781. View

16.

Cao W, Cheng S, Yang J, Feng J, Zhang W, Li Z . Large-scale lipid analysis with C=C location and sn-position isomer resolving power. Nat Commun. 2020; 11(1):375. PMC: 6969141. DOI: 10.1038/s41467-019-14180-4. View

17.

Zheng X, Smith R, Baker E . Recent advances in lipid separations and structural elucidation using mass spectrometry combined with ion mobility spectrometry, ion-molecule reactions and fragmentation approaches. Curr Opin Chem Biol. 2017; 42:111-118. PMC: 5828972. DOI: 10.1016/j.cbpa.2017.11.009. View

18.

Mesa-Herrera F, Taoro-Gonzalez L, Valdes-Baizabal C, Diaz M, Marin R . Lipid and Lipid Raft Alteration in Aging and Neurodegenerative Diseases: A Window for the Development of New Biomarkers. Int J Mol Sci. 2019; 20(15). PMC: 6696273. DOI: 10.3390/ijms20153810. View

19.

Macias L, Garza K, Feider C, Eberlin L, Brodbelt J . Relative Quantitation of Unsaturated Phosphatidylcholines Using 193 nm Ultraviolet Photodissociation Parallel Reaction Monitoring Mass Spectrometry. J Am Chem Soc. 2021; 143(36):14622-14634. PMC: 8579512. DOI: 10.1021/jacs.1c05295. View

20.

Hsu F, Turk J . Structural characterization of unsaturated glycerophospholipids by multiple-stage linear ion-trap mass spectrometry with electrospray ionization. J Am Soc Mass Spectrom. 2008; 19(11):1681-91. PMC: 2639777. DOI: 10.1016/j.jasms.2008.07.023. View