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

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-metacycloheptylprodiginine) 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 ϩ H] ϩ 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

Derivatization of bisphenol A and its analogues with pyridine‐3‐sulfonyl chloride: multivariate optimization and fragmentation patterns by liquid chromatography/Orbitrap mass spectrometry

“…Odd‐electron dissociations, which involve homolytic bond cleavages to yield radical product ions, are commonly observed in electron ionization (EI)‐MS, but they are less common in collision‐induced dissociation under ESI and atmospheric pressure chemical ionization (APCI) conditions 33, 34. Several exceptions to the 'even‐electron rule' have, however, been reported to involve radical eliminations leading to odd‐electron product ions of high stability 35, 36. Other less abundant product ions were obtained after the initial cleavage of the C–C bond between the methylene group and one of the aromatic rings.…”

Synthetic Prodiginine Obatoclax (GX15‐070) and Related Analogues: Anion Binding, Transmembrane Transport, and Cytotoxicity Properties

“…These compounds are well suited to interact with anions such as chloride and bicarbonate. The aniontransport properties of the compounds synthesized were assayed in model phospholipid liposomes by using a chloride-selective-electrode technique and 13 C NMR spectroscopy. The results demonstrated that these compounds are efficient anion exchangers that promote chloride, bicarbonate, and nitrate transport through lipid bilayers at very low concentrations.…”

N-Centered Odd-Electron Ions Formation from Collision-Induced Dissociation of Electrospray Ionization Generated Even-Electron Ions: Single Electron Transfer via Ion/Neutral Complex in the Fragmentation of ProtonatedN,N′-Dibenzylpiperazines and ProtonatedN-Benzylpiperazines

“…When these closed-shell ions are subjected to CID, they commonly dissociate to daughter closed-shell ions and neutral fragments based on 'even-electron rule' [1]. It is rare that an electrospray ionization generated even-electron (EE) ion directly dissociates to form an odd-electron (OE) ion, though exceptions are more common in electron ionization (EI) [1][2][3][4] than in ESI mass spectrometry [5][6][7][8][9][10][11][12]. It is significant and desirable to investigate the underlying mechanism of formation of OE ions from EE ions because such considerations are important for a better understanding of ESI mass spectrometry.…”