Decomposition of nitroimidazole ions: experiment and theory

Abstract

Nitroimidazoles are important compounds with chemotherapeutic applications as antibacterial drugs or as radiosensitizers in radiotherapy. Despite their use in biological applications, little is known about the fundamental properties of these compounds. Understanding the ionization reactions of these compounds is crucial in evaluating the radiosensitization potential and in developing new and more effective drugs. Thus, the present study investigates the decomposition of negative and positive ions of 2-nitroimidazole and 4(5)-nitroimidazole using low- and high-energy Collision-Induced Dissociation (CID) and Electron-Induced Dissociation (EID) by two different mass spectrometry techniques and is supported by quantum chemistry calculations. EID of [M+H](+) leads to more extensive fragmentation than CID and involves many radical cleavages including loss of H˙ leading to the formation of the radical cation, M˙(+). The stability (metastable decay) and the fragmentation (high-energy CID) of the radical cation M˙(+) have been probed in a crossed-beam experiment involving primary electron ionization of the neutral nitroimidazole. Thus, fragments in the EID spectra of [M+H](+) that come from further dissociation of radical cation M˙(+) have been highlighted. The loss of NO˙ radical from M˙(+) is associated with a high Kinetic Energy Release (KER) of 0.98 eV. EID of [M-H](-) also leads to additional fragments compared to CID, however, with much lower cross section. Only EID of [M+H](+) leads to a slight difference in the decomposition of 2-nitroimidazole and 4(5)-nitroimidazole.

Isomer Selectivity in Low‐Energy Electron Attachment to Nitroimidazoles

“…In this case, two electrons are presenti nf ormerly unoccupied orbitals. [19] Simple bond cleavages related to loss of neutralHC,NO 2 C, HONO,and formation of NO 2 À À In the following we discuss formation of anionsw hich can be formed by simple bond cleavages, that is, the loss of aH C radical [Eq. [10] The loss of NOC radical [Eq.…”

“…(4)],w hich is ah ighly exothermic DEA channel ( Figure S3 and Ta ble S1), was also observed in DEA to other aromatic nitro compounds, [18] andw as shown to be one of the dominant channels in the decomposition of nitroimidazoles irrespective of the charges tate of the precursor. [19] Simple bond cleavages related to loss of neutralHC,NO 2 C, HONO,and formation of NO 2 À À In the following we discuss formation of anionsw hich can be formed by simple bond cleavages, that is, the loss of aH e À þ NI !½NI*C À !½NI À H À þ HC ð5Þ e À þ NI !½NI*C À ! NO 2 À þ½NI À NO 2 C ð6Þ e À þ NI !½NI*C À !½NI À NO 2 À þ NO 2 C ð7Þ e À þ NI !½NI*C À !½NI À HONOC À þ HONO ð8Þ…”

Fragmentation patterns of 4(5)‐nitroimidazole and 1‐methyl‐5‐nitroimidazole—The effect of the methylation

“…Shortly after this, Tanzer et al showed that methylation of nitroimidazole at the N1 site completely blocks the rich chemistry induced by the attachment of low energy free electrons . In 2015, a study on 2‐ and 4(5)‐nitroimidazole ions using collision induced dissociation and electron induced dissociation reported different fragmentation in 2‐ and 4(5)‐nitroimidazole in the case of electron induced dissociation …”

“…The skeletal formulae of the sample molecules are presented in Figure ; 5NIZ isomer does not exist in the condensed phase, but tautomerizes spontaneously to its 4NIZ isomer . Upon evaporation, however, 4NIZ partially undergoes isomerization into 5‐nitroimidazole resulting in the molecular ratio of 1:0.70 of 4NIZ to 5NIZ .…”

Electron‐induced dissociation (EID) for structure characterization of glycerophosphatidylcholine: determination of double‐bond positions and localization of acyl chains

“…The application of electron‐based dissociation techniques for singly charged gaseous ions, referred here as EID, has received notable interest of late but has a rich history dating back to the work of Cody and Freiser . We present the use of EID to structurally characterize PC ions produced via matrix‐assisted laser desorption ionization (MALDI) on a Fourier transform ion cyclotron resonance (FT‐ICR) mass spectrometer.…”