Unusual odd-electron fragments from even-electron protonated prodiginine precursors using positive-ion electrospray tandem mass spectrometry.
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.
Chen
Kan
K
Department of Chemistry, University of New Orleans, New Orleans, Louisiana 70148, USA.
Rannulu
Nalaka S
NS
Cai
Yang
Y
Lane
Pat
P
Liebl
Andrea L
AL
Rees
Bernard B
BB
Corre
Christophe
C
Challis
Gregory L
GL
Cole
Richard B
RB
D000900:Anti-Bacterial Agents / Q000737:chemistry; D004583:Electrons; D007477:Ions; D015394:Molecular Structure; D010860:Pigments, Biological / Q000737:chemistry; D011353:Prodigiosin / Q000031:analogs & derivatives* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013816:Thermodynamics
D000900:Anti-Bacterial Agents; D007477:Ions; D010860:Pigments, Biological; C528939:streptorubin B; C528938:undecylprodiginine; C010307:prodiginine; D011353:Prodigiosin
Biochem Biophys Res Commun. 1997 Aug 28;237(3):543-7
9299400
Adv Appl Microbiol. 2000;47:1-32
12876793
Toxicol Sci. 2005 Jun;85(2):870-9
15788728
Chem Commun (Camb). 2006 Oct 14;(38):3981-3
17003872
J Org Chem. 1999 Oct 29;64(22):8275-8280
11674748
Transplant Proc. 2001 Nov-Dec;33(7-8):3272-3
11750401
J Mass Spectrom. 2007 Aug;42(8):1024-44
17605143
J Antibiot (Tokyo). 1971 Sep;24(9):636-40
5132249
Biochem Pharmacol. 2003 Oct 15;66(8):1447-52
14555220
Drug Metab Dispos. 2004 Feb;32(2):272-9
14744951
Chem Biol. 2008 Feb;15(2):137-48
18291318
J Antibiot (Tokyo). 1991 Feb;44(2):187-91
2010358
Biochem Biophys Res Commun. 1960 Aug;3:146-9
13843029
Nucleic Acids Res. 2005 Dec 13;33(22):7066-73
16352867
Biochem Pharmacol. 2004 Oct 1;68(7):1345-52
15345324
Curr Med Chem Anticancer Agents. 2001 Aug;1(2):195-218
12678767
Angew Chem Int Ed Engl. 2003 Aug 11;42(31):3582-603
12916029
Curr Cancer Drug Targets. 2003 Feb;3(1):57-65
12570661
Ann N Y Acad Sci. 2003 Dec;1010:178-81
15033716
CRC Crit Rev Microbiol. 1975 May;3(4):469-85
1095305
Appl Microbiol. 1973 Mar;25(3):396-402
4572893
Phys Rev B Condens Matter. 1992 Nov 15;46(20):12947-12954
10003333
J Immunol. 1999 Jun 15;162(12):7102-9
10358154
Biochem Biophys Res Commun. 2007 Nov 16;363(2):322-8
17869216
Chem Biol. 2001 Aug;8(8):817-29
11514230
J Am Soc Mass Spectrom. 2008 Dec;19(12):1856-66
18774733
J Mass Spectrom. 2006 Oct;41(10):1277-86
16983735