Houée-Levin C, Gardès-Albert M, Rouscilles A, Ferradini C, Hickel B
Laboratoire de Chimie Physique, URA 400, Université Paris V, France.
Biochemistry. 1991 Aug 20;30(33):8216-22. doi: 10.1021/bi00247a018.
The one-electron reduction of daunorubicin, a quinonic antitumor antibiotic, intercalated in DNA was studied by pulse radiolysis using carboxyl radicals as reductants. The reaction's first stage is the daunorubicin semiquinone formation (k = 1.9 x 10(8) mol-1.dm3.s-1) in a way entirely consistent with a simple competition between .COO- disproportionation and the drug reduction. The semiquinone drug disappears by a first-order reaction (k = 1340 s-1) producing the hydroquinone form. This reaction leads to an equilibrium similar to the one without DNA and the equilibrium constant is very close to its value free in water (Kc approximately 25). In addition, the stoichiometry of the first-order reaction is the one of a dismutation process. Therefore, it appears that the disproportionation occurs along an intramolecular path across DNA. This migration takes place under our experimental conditions, over a distance of ca. 100 base pairs, with a mobility of ca. 4.4 X 10(-11) m2.V-1.s-1, similar in magnitude to an excess electron mobility in doped organic polymers.
以羧基自由基作为还原剂，采用脉冲辐解技术研究了嵌入DNA中的醌类抗肿瘤抗生素柔红霉素的单电子还原反应。反应的第一阶段是柔红霉素半醌的形成（k = 1.9 x 10(8) mol-1.dm3.s-1），其方式与.COO-歧化反应和药物还原之间的简单竞争完全一致。半醌药物通过一级反应（k = 1340 s-1）消失，生成对苯二酚形式。该反应导致了一个类似于无DNA时的平衡，平衡常数非常接近其在水中的自由值（Kc约为25）。此外，一级反应的化学计量是歧化过程的化学计量。因此，似乎歧化反应是沿着穿过DNA的分子内路径发生的。在我们的实验条件下，这种迁移发生在约100个碱基对的距离上，迁移率约为4.4 X 10(-11) m2.V-1.s-1，其大小与掺杂有机聚合物中过量电子的迁移率相似。
