Gas-Phase Stability of Negatively Charged Organophosphate Metabolites Produced by Electrospray Ionization and Matrix-Assisted Laser Desorption/Ionization

Overview

Journal J Am Soc Mass Spectrom

Specialty Chemistry

Date 2017 Sep 7

PMID 28875264

Citations 1

Authors

Daiki Asakawa

Hajime Mizuno

Toshimasa Toyooka

Affiliations

Soon will be listed here.

Abstract

The formation mechanisms of singly and multiply charged organophosphate metabolites by electrospray ionization (ESI) and their gas phase stabilities were investigated. Metabolites containing multiple phosphate groups, such as adenosine 5'-diphosphate (ADP), adenosine 5'-triphosphate (ATP), and D-myo-inositol-1,4,5-triphosphate (IP) were observed as doubly deprotonated ions by negative-ion ESI mass spectrometry. Organophosphates with multiple negative charges were found to be unstable and often underwent loss of PO, although singly deprotonated analytes were stable. The presence of fragments due to the loss of PO in the negative-ion ESI mass spectra could result in the misinterpretation of analytical results. In contrast to ESI, matrix-assisted laser desorption ionization (MALDI) produced singly charged organophosphate metabolites with no associated fragmentation, since the singly charged anions are stable. The stability of an organophosphate metabolite in the gas phase strongly depends on its charge state. The fragmentations of multiply charged organophosphates were also investigated in detail through density functional theory calculations. Graphical Abstract.

Citing Articles

Gas-Phase Internal Ribose Residue Loss from Mg-ATP and Mg-ADP Complexes: Experimental and Theoretical Evidence for Phosphate-Mg-Adenine Interaction.

Franska M, Stzycka O, Jankowski W, Hoffmann M J Am Soc Mass Spectrom. 2022; 33(8):1474-1479.

PMID: 35796751 PMC: 9354248. DOI: 10.1021/jasms.2c00071.

References

Iavarone A, Jurchen J, Williams E . Effects of solvent on the maximum charge state and charge state distribution of protein ions produced by electrospray ionization. J Am Soc Mass Spectrom. 2000; 11(11):976-85. PMC: 1414794. DOI: 10.1016/S1044-0305(00)00169-0. View

Gabelica V, Schulz E, Karas M . Internal energy build-up in matrix-assisted laser desorption/ionization. J Mass Spectrom. 2004; 39(6):579-93. DOI: 10.1002/jms.651. View

ALBERTY R, Smith R, Bock R . The apparent ionization constants of the adenosinephosphates and related compounds. J Biol Chem. 1951; 193(1):425-34. View

Gross D, Schnier P, Rodriguez-Cruz S, Fagerquist C, Williams E . Conformations and folding of lysozyme ions in vacuo. Proc Natl Acad Sci U S A. 1996; 93(7):3143-8. PMC: 39776. DOI: 10.1073/pnas.93.7.3143. View

Dong Y, Guella G, Mattivi F, Franceschi P . High production of small organic dicarboxylate dianions by DESI and ESI. J Am Soc Mass Spectrom. 2015; 26(3):386-9. DOI: 10.1007/s13361-014-1065-y. View

Drahos , Heeren , Collette , De Pauw E , Vekey . Thermal energy distribution observed in electrospray ionization. J Mass Spectrom. 1999; 34(12):1373-9. DOI: 10.1002/(SICI)1096-9888(199912)34:12<1373::AID-JMS907>3.0.CO;2-#. View

Yamaguchi K . Cold-spray ionization mass spectrometry: principle and applications. J Mass Spectrom. 2003; 38(5):473-90. DOI: 10.1002/jms.488. View

Iavarone A, Williams E . Mechanism of charging and supercharging molecules in electrospray ionization. J Am Chem Soc. 2003; 125(8):2319-27. PMC: 1343448. DOI: 10.1021/ja021202t. View

Susa A, Xia Z, Tang H, Tainer J, Williams E . Charging of Proteins in Native Mass Spectrometry. J Am Soc Mass Spectrom. 2016; 28(2):332-340. PMC: 5283922. DOI: 10.1007/s13361-016-1517-7. View

10.

Luo G, Marginean I, Vertes A . Internal energy of ions generated by matrix-assisted laser desorption/ionization. Anal Chem. 2003; 74(24):6185-90. DOI: 10.1021/ac020339z. View

11.

Harrison A . Charge-separation reactions of doubly-protonated peptides: effect of peptide chain length. J Am Soc Mass Spectrom. 2009; 20(10):1890-5. DOI: 10.1016/j.jasms.2009.06.013. View

12.

Kharlamova A, Prentice B, Huang T, McLuckey S . Electrospray droplet exposure to gaseous acids for the manipulation of protein charge state distributions. Anal Chem. 2010; 82(17):7422-9. PMC: 2940272. DOI: 10.1021/ac101578q. View

13.

Iavarone A, Jurchen J, Williams E . Supercharged protein and peptide ions formed by electrospray ionization. Anal Chem. 2001; 73(7):1455-60. PMC: 1414801. DOI: 10.1021/ac001251t. View

14.

Kharlamova A, McLuckey S . Negative electrospray droplet exposure to gaseous bases for the manipulation of protein charge state distributions. Anal Chem. 2010; 83(1):431-7. PMC: 3012141. DOI: 10.1021/ac1027319. View

15.

Wang G, Colecor R . Effects of solvent and counterion on ion pairing and observed charge states of diquaternary ammonium salts in electrospray ionization mass spectrometry. J Am Soc Mass Spectrom. 2013; 7(10):1050-8. DOI: 10.1016/1044-0305(96)00051-7. View

16.

Karas M, Hillenkamp F . Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. Anal Chem. 1988; 60(20):2299-301. DOI: 10.1021/ac00171a028. View

17.

Ogorzalek Loo R, Smith R . Investigation of the gas-phase structure of electrosprayed proteins using ion-molecule reactions. J Am Soc Mass Spectrom. 2013; 5(4):207-20. DOI: 10.1016/1044-0305(94)85011-9. View

18.

Liigand P, Kaupmees K, Kruve A . Ionization Efficiency of Doubly Charged Ions Formed from Polyprotic Acids in Electrospray Negative Mode. J Am Soc Mass Spectrom. 2016; 27(7):1211-8. DOI: 10.1007/s13361-016-1384-2. View

19.

Fenn J, Mann M, Meng C, Wong S, Whitehouse C . Electrospray ionization for mass spectrometry of large biomolecules. Science. 1989; 246(4926):64-71. DOI: 10.1126/science.2675315. View

20.

Gabelica V, De Pauw E . Internal energy and fragmentation of ions produced in electrospray sources. Mass Spectrom Rev. 2004; 24(4):566-87. DOI: 10.1002/mas.20027. View