J. Heyrovsky Institute of Physical Chemistry of the Academy of Sciences of the Czech Republic, v.v.i., Dolejskova 3, 182 23 Prague, Czech Republic.
Bioelectrochemistry. 2010 Jun;78(2):118-23. doi: 10.1016/j.bioelechem.2009.08.008. Epub 2009 Aug 23.
Cytotoxic properties of radiosensitizers are due to the fact that, in the metabolic pathway, these compounds undergo one-electron reduction to generate radical anions. In this study we focused our interest on the electrochemical transfer of the first electron on radiosensitizer Etanidazole (ETN) and, consequently, on the ETN radical-anion formation in the buffered aqueous media. ETN was electrochemically treated in the broad pH range at various scan rates. Three reduction peaks and one oxidation peak were found. At strong alkaline pH the four-electron reduction peak was separated into one-electron and three-electron reductions. Under these conditions the standard rate constant k(0) for the redox couple ETN-NO(2)+e(-) <--> ETN-NO(2)(*-) was calculated. Moreover, the value of a so called E(7)(1) potential that accounts for the energy necessary to transfer the first electron to an electroactive group at pH=7 in aqueous medium to form a radical anion was also determined. The obtained value of E(7)(1) indicates that lower energy compared to the other possible chemical radiosensitizers is necessary for the system to transfer the first electron to ETN. On the other hand, the necessity of the strong alkaline pH may decrease the ability of ETN to act as hypoxic radiosensitizer in the human body.
增敏剂的细胞毒性特性是由于在代谢途径中，这些化合物经历单电子还原生成自由基阴离子。在这项研究中，我们将兴趣集中在增敏剂依替米硝唑（ETN）的第一电子电化学转移上，因此，我们关注了在缓冲水溶液介质中 ETN 自由基阴离子的形成。在不同的扫描速率下，在宽 pH 范围内对 ETN 进行了电化学处理。发现了三个还原峰和一个氧化峰。在强碱性 pH 下，四电子还原峰分为一电子和三电子还原。在这些条件下，计算了 ETN-NO(2)+e(-) <--> ETN-NO(2)(*-)氧化还原对的标准速率常数 k(0)。此外，还确定了所谓的 E(7)(1)电位的值，该值表示在 pH=7 的水溶液中向电活性基团转移第一个电子以形成自由基阴离子所需的能量。获得的 E(7)(1)值表明，与其他可能的化学增敏剂相比，系统向 ETN 转移第一个电子所需的能量更低。另一方面，强碱性 pH 的必要性可能会降低 ETN 在人体中作为乏氧增敏剂的能力。
