Institut für Ionenphysik und Angewandte Physik, Leopold-Franzens-Universität Innsbruck, Technikerstrasse 25, A-6020, Innsbruck, Austria.
Center for Biomolecular Sciences Innsbruck (CMBI), Leopold-Franzens-Universität Innsbruck, Technikerstrasse 25, A-6020, Innsbruck, Austria.
Angew Chem Int Ed Engl. 2020 Sep 21;59(39):17177-17181. doi: 10.1002/anie.202006675. Epub 2020 Aug 4.
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 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.
替拉扎明（TPZ）因其对缺氧肿瘤细胞具有潜在的高度选择性毒性，已在放射化学疗法的临床试验中进行了测试。据推测，TPZ 在溶液中的初始还原后，可能会形成羟基自由基或苯并三嗪基自由基等生物活性自由基。在本工作中，我们研究了气相中低能电子对 TPZ 的附着，并通过质谱研究了形成的 TPZ 阴离子的分解。我们观察到（TPZ-OH）阴离子的形成伴随着羟基自由基的解离，这是附着低能电子时迄今为止最丰富的反应途径。量子化学计算表明，NH 三角化是电子附着后反应动力学的关键反应坐标。我们提出了 OH 漫游机制，用于竞争 OH 解离的其他观察到的反应通道。
