Reactions in Tirapazamine Induced by the Attachment of Low-Energy Electrons: Dissociation Versus Roaming of OH

Eugene Arthur-Baidoo, João Ameixa, Patrick Ziegler, Filipe Ferreira da Silva, Milan Ončák, Stephan Denifl

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
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Abstract

Tirapazamine (TPZ) has been tested in clinical trials on radio-chemotherapy due to its potential highly selective toxicity towards hypoxic tumor cells. It was suggested that either the hydroxyl radical or benzotriazinyl radical may form as bioactive radical after the initial reduction of TPZ in solution. In the present work, we studied low-energy electron attachment to TPZ in the gas phase and investigated the decomposition of the formed TPZ anion by mass spectrometry. We observed the formation of the (TPZ–OH) anion accompanied by the dissociation of the hydroxyl radical as by far the most abundant reaction pathway upon attachment of a low-energy electron. Quantum chemical calculations suggest that NH2 pyramidalization is the key reaction coordinate for the reaction dynamics upon electron attachment. We propose an OH roaming mechanism for other reaction channels observed, in competition with the OH dissociation.

Original languageEnglish
Pages (from-to)17177-17181
Number of pages5
JournalAngewandte Chemie - International Edition
Volume59
Issue number39
DOIs
Publication statusPublished - 21 Sep 2020

Keywords

  • dissociative electron attachment
  • gas-phase
  • hypoxic cytotoxins
  • radiosensitizers
  • tirapazamine

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