High-energy collision-induced dissociation of radiosensitizer anions: Nimorazole and metronidazole

International audienceThe formation of radical anions of nitroimidazolic radiosensitizers, nimorazole and metronidazole, and their unimolecular dissociation reactions upon high-energy collisions with He gas were investigated with a double focusing mass spectrometer equipped with an electrospray ionization (ESI) source. Radical anions of both, nimorazole and metronidazole, are readily formed in the ESI process, while for the metronidazole also the deprotonated anion is formed. A variety of dissociation channels is observed and the associated kinetic energy released in the dissociation for most of these channels is reported. The marker anion NO2 − is observed in the dissociation of all studied anions. The release of NO• radical from the radical anions is associated with surprisingly small kinetic energy release in comparison to simple nitroimidazoles. On the other hand, the highest kinetic energy release is noted for the release of the neutral side group from N1 position of the imidazole ring, which suggests that the substitution at the N1 plays a crucial role in the decomposition of anions of radiosensitizer

Understanding the action of radiosensitizers in radiotherapy by mass spectrometry and theory

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Binding preference of nitroimidazolic radiosensitizers to nucleobases and nucleosides probed by electrospray ionization mass spectrometry and density functional theory

International audienceNitroimidazolic radiosensitizers are used in radiation therapy to selectively sensitize cancer cells deprived of oxygen, and the actual mechanism of radiosensitization is still not understood. Selecting five radiosensitizers (1-methyl-5-nitroimidazole, ronidazole, ornidazole, metronidazole, and nimorazole) with a common 5-nitroimidazolic ring with different substitutions at N1 and C2 positions of the imidazole moiety, we investigate here their binding to nucleobases (A, T, G, and C) and nucleosides (As, Td, Gs, and Cd) via the positive electrospray ionization mass spectrometry experiments. In addition, quantum chemical calculations at the M062x/6-311+G(d,p) level of theory and basis set were used to determine binding energies of the proton bound dimers of a radiosensitizer and a nucleobase. The positive electrospray ionization leads to the formation of proton bound dimers of all radiosensitizers except 1-methyl-5-nitroimidazole in high abundance with C and smaller abundance with G. Ronidazole and metronidazole formed less abundant dimers also with A, while no dimers were observed to be formed at all with T. In contrast to the case of the nucleoside Td, the dimer intensity is as high as that with Cd, while the abundance of the dimer with Gs is smaller than that of the former. The experimental results are consistent with the calculations of binding energies suggesting proton bound dimers with C and G to be the strongest bound ones. Finally, a barrier-free proton transfer is observed when protonated G or C approaches the nitroimidazole ring

Nitroimidazolic radiosensitizers investigated by electrospray ionization time-of-flight mass spectrometry and density functional theory

International audienceRadiosensitizers are important compounds used in radiotherapy to enhance tumor control of radioresistant hypoxic tumors. Despite their use in biological applications, little is known about the fundamental properties of these compounds. Nevertheless, understanding the ionization reactions of these compounds is crucial in evaluating the potential of radiosensitizers and in developing new and more effective drugs. The present study investigates the positive and negative electrospray ionization and subsequent low-energy collision-induced dissociation reactions of ions derived from 1-methyl-5-nitroimidazole, metronidazole, ronidazole, ornidazole and nimorazole using a hybrid quadrupole time of flight mass spectrometer equipped with an electrospray ionization source (ESI-Q-TOF). Quantum chemical calculations are performed to obtain in addition the proton affinities, deprotonation energies, and electron affinities of the investigated compounds

2-Cyano-3-(2-thienyl)acrylic Acid as a New MALDI Matrix for the Analysis of a Broad Spectrum of Analytes

International audienceA low-cost synthetic 2-cyano-3-(2-thienyl)acrylic acid (CTA) is developed as a new MALDI matrix for the analysis of various classes of compounds such as lipids (e.g., fatty acids), peptides, proteins, saccharides, natural products (i.e., iridoids), PEGs, and organometallics in the positive-ion mode. The difficulty in the analysis of high molecular mass PEGs was overcome by using CTA as matrix even at low concentrations. Both high molecular mass proteins and peptides were successfully analyzed using CTA. The mass spectra of all of the studied analytes with CTA showed high signal-to-noise (S/N) ratios and spectral resolutions when compared to other conventional matrices such as SA, DHB, DT, and HCCA. However, in the case of peptide analysis with CTA, the resulting mass spectra are found to be similar to that of the well-established HCCA matrix. On the basis of the physicochemical properties of the analytes, the CTA works as a proton/cation or electron-transfer matrix. It proves that the CTA can be used as a common matrix for the analysis of majority classes of analytes instead of using a specific matrix for the particular class of analytes. Further, the CTA provides an advantage in the analysis of unknown samples as it rules out ambiguity in the selection of particular matrix and it may also offer a complete profile of the tissue surface in the MALDI-imaging experiments