Premium
Reactions in Tirapazamine Induced by the Attachment of Low‐Energy Electrons: Dissociation Versus Roaming of OH
Author(s) -
ArthurBaidoo Eugene,
Ameixa João,
Ziegler Patrick,
Ferreira da Silva Filipe,
Ončák Milan,
Denifl Stephan
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202006675
Subject(s) - tirapazamine , chemistry , dissociation (chemistry) , photochemistry , ion , hydroxyl radical , roaming , radical , organic chemistry , telecommunications , biochemistry , cytotoxicity , computer science , in vitro
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 NH 2 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.