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Unusual odd-electron fragments from even-electron protonated prodiginine precursors using positive-ion electrospray tandem mass spectrometry

Journal of the American Society for Mass Spectrometry volume 19, pages 1856–1866 (2008)Cite this article

Abstract

Reports of anticancer and immunosuppressive properties have spurred recent interest in the bacterially produced prodiginines. We use electrospray tandem mass spectrometry (ES-MS/MS) to investigate prodigiosin, undecylprodiginine, and streptorubin B (butyl-meta-cycloheptylprodiginine) and to explore their fragmentation pathways to explain the unusual methyl radical loss and consecutive fragment ions that dominate low-energy collision-induced dissociation (CID) mass spectra. The competition between the formation of even-electron ions and radical ions is examined in detail. Theoretical calculations are used to optimize the structures and calculate the energies of both reactants and products using the Gaussian 03 program. Results indicate that protonation occurs on the nitrogen atom that initially held no hydrogen, thus allowing formation of a pseudo-seven-membered ring that constitutes the most stable ground state [M+H]+ structure. From this precursor, experimental data show that methyl radical loss has the lowest apparent threshold but, alternatively, even-electron fragment ions can be formed by loss of a methanol molecule. Computational modeling indicates that methyl radical loss is the more endothermic process in this competition, but the lower apparent threshold associated with methyl radical loss points to a lower kinetic barrier. Additionally, this characteristic and unusual loss of methyl radical (in combination with weaker methanol loss) from each prodiginine is useful for performing constant neutral loss scans to quickly and efficiently identify all prodiginines in a complex biological mixture without any clean-up or purification. The feasibility of this approach has been proven through the identification of a new, low-abundance prodigiosin analog arising from Hahella chejuensis.

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Authors and Affiliations

  1. Department of Chemistry, University of New Orleans, 2000 Lakeshore Dr., 70148, New Orleans, LA, USA

    Kan Chen, Nalaka S. Rannulu, Yang Cai, Pat Lane & Richard B. Cole

  2. The Research Institute for Children, Children’s Hospital of New Orleans, New Orleans, Louisiana, USA

    Yang Cai

  3. Department of Biological Sciences, University of New Orleans, New Orleans, Louisiana, USA

    Andrea L. Liebl & Bernard B. Rees

  4. Department of Chemistry, University of Warwick, Coventry, United Kingdom

    Christophe Corre & Gregory L. Challis

Authors
  1. Kan Chen
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  2. Nalaka S. Rannulu
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  3. Yang Cai
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  4. Pat Lane
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  5. Andrea L. Liebl
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  7. Christophe Corre
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  8. Gregory L. Challis
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  9. Richard B. Cole
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Correspondence to Richard B. Cole.

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Published online August 9, 2008

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Chen, K., Rannulu, N.S., Cai, Y. et al. Unusual odd-electron fragments from even-electron protonated prodiginine precursors using positive-ion electrospray tandem mass spectrometry. J Am Soc Mass Spectrom 19, 1856–1866 (2008). https://doi.org/10.1016/j.jasms.2008.08.002

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  • DOI: https://doi.org/10.1016/j.jasms.2008.08.002

Keywords

  • Neutral Loss
  • Fragmentation Pathway
  • Tandem Mass Spectrum
  • Prodigiosin
  • Electrospray Tandem Mass Spectrometry