How to Find Out Whether a 5-Substituted Uracil Could Be a Potential DNA Radiosensitizer
How to Find Out Whether a 5-Substituted Uracil Could Be a Potential DNA Radiosensitizer
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DOI：
10.1021/jz401358w
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发表时间：
2013-09-05
影响因子：
5.7
通讯作者：
Bowen, Kit H.
中科院分区：
文献类型：
--
作者：
Chomicz, Lidia;Zdrowowicz, Magdalena;Bowen, Kit H.
5-取代尿嘧啶被整合到基因组DNA中，如果它们能被敏化，与水合电子反应解离，就可以用于人类癌症的放射治疗。采用B3LYP/6-31++G(d，p)方法，计算了一系列尿嘧啶类化合物的电子亲和能和与相应阴离子解离有关的能量分布。我们证明，要使尿嘧啶类似物成为有效的电子受体，尿嘧啶取代基必须具有显著的吸电子能力。另一方面，为了确保阴离子的有效解离，将取代基和尿嘧啶残基结合在一起的化学键应该相对较弱。我们的理论预测与我们的负离子光电子能谱实验结果非常一致。我们提出了两种新的潜在增敏剂，它们似乎具有所需的特性，尽管它们从未在放射生物学实验中进行过测试。
Incorporated into genomic DNA, 5-substituted uracils could be employed in human cancer radiotherapy if they could be sensitized to dissociate upon reaction with hydrated electrons. Using the B3LYP/6-31++G(d,p) method, we calculate electron affinities and energy profiles related to the dissociation of the respective anions for a series of uracil derivatives. We demonstrate that for a uracil analogue to be an efficient electron acceptor the uracil substituent has to possess significant electron-withdrawing power. On the other hand, in order to ensure effective dissociation of the anion, the chemical bond holding together the substituent and uracil residue should be relatively weak. Our theoretical predictions are in excellent agreement with the results of our negative ion photoelectron spectroscopy experiments. We propose two new potential sensitizers that seem to possess the required properties, although they have never been tested in radiobiological experiments.