Electron‐Induced Reactions in 3‐Bromopyruvic Acid

Silva, F. Ferreira da; Varella, Márcio T. do N.; Jones, Nykola C.; Hoffmann, Søren Vrønning; Denifl, Stephan; Bald, Ilko; Kopyra, Janina

doi:10.1002/chem.201806132

Cited by 8 publications

(6 citation statements)

References 45 publications

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“…Previous studies showed that DEA can be an effective process in breaking bonds and hence generates radicals at electron energies considerably below typical bond dissociation energies [10,11,12,13,14]. Such behavior was also observed in DEA studies with radiosensitizers like modified nucleobases [5,6,17,18,19,20]. By modification of the native nucleobase by highly electron affinic side groups, an increase of the DEA cross section can be achieved.…”

Section: Introductionmentioning

confidence: 75%

Reactions in the Radiosensitizer Misonidazole Induced by Low-Energy (0–10 eV) Electrons

Meißner

Feketeová

Illenberger

et al. 2019

IJMS

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Misonidazole (MISO) was considered as radiosensitizer for the treatment of hypoxic tumors. A prerequisite for entering a hypoxic cell is reduction of the drug, which may occur in the early physical-chemical stage of radiation damage. Here we study electron attachment to MISO and find that it very effectively captures low energy electrons to form the non-decomposed molecular anion. This associative attachment (AA) process is exclusively operative within a very narrow resonance right at threshold (zero electron energy). In addition, a variety of negatively charged fragments are observed in the electron energy range 0–10 eV arising from dissociative electron attachment (DEA) processes. The observed DEA reactions include single bond cleavages (formation of NO2−), multiple bond cleavages (excision of CN−) as well as complex reactions associated with rearrangement in the transitory anion and formation of new molecules (loss of a neutral H2O unit). While any of these AA and DEA processes represent a reduction of the MISO molecule, the radicals formed in the course of the DEA reactions may play an important role in the action of MISO as radiosensitizer inside the hypoxic cell. The present results may thus reveal details of the molecular description of the action of MISO in hypoxic cells.

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Section: Introductionmentioning

confidence: 75%

Reactions in the Radiosensitizer Misonidazole Induced by Low-Energy (0–10 eV) Electrons

Meißner

Feketeová

Illenberger

et al. 2019

IJMS

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“…3-BP treatment probably leads to generation of ROS through its cellular metabolism, by damaging mitochondria and as a result of GSH depletion [20,26,27]. Recent studies also show that 3-BP may directly disrupt the OXPHOS electron transport chain in mitochondria and thereby induce ROS [65]. It is also known that at least some chemical oxidants such as H 2 O 2 or bleomycin are able to induce both SSBs and DSBs [66][67][68].…”

Section: Discussionmentioning

confidence: 99%

“…3-BP exhibits broad activities, from anticancer [3,69], antifungal [65,70] to antibacterial [71] and anti-algal [72]. 3-BP, in the cell, acts pleiotropically by disrupting various processes (Figure 8).…”

Section: Discussionmentioning

confidence: 99%

The Anticancer Drug 3-Bromopyruvate Induces DNA Damage Potentially Through Reactive Oxygen Species in Yeast and in Human Cancer Cells

Cal

Matyjaszczyk

Litwin

et al. 2020

Cells

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3-bromopyruvate (3-BP) is a small molecule with anticancer and antimicrobial activities. 3-BP is taken up selectively by cancer cells’ mono-carboxylate transporters (MCTs), which are highly overexpressed by many cancers. When 3-BP enters cancer cells it inactivates several glycolytic and mitochondrial enzymes, leading to ATP depletion and the generation of reactive oxygen species. While mechanisms of 3-BP uptake and its influence on cell metabolism are well understood, the impact of 3-BP at certain concentrations on DNA integrity has never been investigated in detail. Here we have collected several lines of evidence suggesting that 3-BP induces DNA damage probably as a result of ROS generation, in both yeast and human cancer cells, when its concentration is sufficiently low and most cells are still viable. We also demonstrate that in yeast 3-BP treatment leads to generation of DNA double-strand breaks only in S-phase of the cell cycle, possibly as a result of oxidative DNA damage. This leads to DNA damage, checkpoint activation and focal accumulation of the DNA response proteins. Interestingly, in human cancer cells exposure to 3-BP also induces DNA breaks that trigger H2A.X phosphorylation. Our current data shed new light on the mechanisms by which a sufficiently low concentration of 3-BP can induce cytotoxicity at the DNA level, a finding that might be important for the future design of anticancer therapies.

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“…The reaction enthalpy of electron-induced dehydrogenation of HCOOH can be described as a balance between the electron affinity of the HCOO (i.e., 3.17 eV [ 31 ]) and the HCOO-H bond dissociation energy (i.e., 4.47 eV [ 31 ]). In contrast, for the acetic acid, the pyruvic acid, the benzoic acid and the bromopyruvic acid this threshold is considerably below 1 eV [ 32 , 33 , 34 , 35 ]. In the present case, for both molecules, we observe the threshold for the molecular dehydrogenation near 0 eV ( Figure 2 a, m/z 131 and Figure 3 a, m/z 191).…”

Section: Resultsmentioning

confidence: 99%

Experimental and Theoretical Studies of Dissociative Electron Attachment to Metabolites Oxaloacetic and Citric Acids

Kopyra

Wierzbicka

Tulwin

et al. 2021

IJMS

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In this contribution the dissociative electron attachment to metabolites found in aerobic organisms, namely oxaloacetic and citric acids, was studied both experimentally by means of a crossed-beam setup and theoretically through density functional theory calculations. Prominent negative ion resonances from both compounds are observed peaking below 0.5 eV resulting in intense formation of fragment anions associated with a decomposition of the carboxyl groups. In addition, resonances at higher energies (3–9 eV) are observed exclusively from the decomposition of the oxaloacetic acid. These fragments are generated with considerably smaller intensities. The striking findings of our calculations indicate the different mechanism by which the near 0 eV electron is trapped by the precursor molecule to form the transitory negative ion prior to dissociation. For the oxaloacetic acid, the transitory anion arises from the capture of the electron directly into some valence states, while, for the citric acid, dipole- or multipole-bound states mediate the transition into the valence states. What is also of high importance is that both compounds while undergoing DEA reactions generate highly reactive neutral species that can lead to severe cell damage in a biological environment.

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Electron‐Induced Reactions in 3‐Bromopyruvic Acid

Cited by 8 publications

References 45 publications

Reactions in the Radiosensitizer Misonidazole Induced by Low-Energy (0–10 eV) Electrons

Reactions in the Radiosensitizer Misonidazole Induced by Low-Energy (0–10 eV) Electrons

The Anticancer Drug 3-Bromopyruvate Induces DNA Damage Potentially Through Reactive Oxygen Species in Yeast and in Human Cancer Cells

Experimental and Theoretical Studies of Dissociative Electron Attachment to Metabolites Oxaloacetic and Citric Acids

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