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首页> 外文期刊>Journal of Physical Organic Chemistry >Theoretical prediction of size-expansion effect on the C8-site activity in the modified guanine-cytosine analogs
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Theoretical prediction of size-expansion effect on the C8-site activity in the modified guanine-cytosine analogs

机译：修饰的鸟嘌呤-胞嘧啶类似物的C8位点活性的尺寸扩展效应的理论预测

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Homo/hetero ring-expanded DNA analogs have been shown to be rationally modified DNA motifs with improvedphysical or biological properties. In this work, using density functional theory, the stability of these artificial DNA basepairs was examined with regard to three aspects associated with DNA damage, namely deprotonation, H-abstraction,and H-radical addition. The effect of size expansion on C8 activity was investigated because C8-oxidative guanine (G)is one of the most important products of DNA damage. Computational results indicate that the insertion of anaromatic spacer ring in G considerably decreases the electron density over the C8 site, leading to easier deprotonationor H-abstraction from the C8 site and more difficult ft-radical attack on the C8 site. However, the oppositephenomenon is observed if the spacer ring is antiaromatic, because of the increased electron density over the C8site. Moreover, these effects are more prominent the larger the aromaticity or antiaromaticity of the spacer ring.Further analyses, using natural bond orbitals (NBOs) and the nucleus-independent chemical shift (NICS) index ofaromaticity, indicate that the changes of the electron distribution over the C8 site arise because the aromatic spacerring, involved in the conjugation structure, increases the electron delocalization from the electron-rich imidazole ringto the diatropic six-membered rings, while the antiaromatic spacer ring acts as an electron-donating group, not onlyinhibiting the above electron delocalization, but also slightly increasing the electron density over the C8 site. Theimproved stability of these size-expanded base pairs in different DNA-damaged environments may encourage theiruse in practical applications.
机译：同源/杂环扩展的DNA类似物已被证明是合理修​​饰的DNA基序，具有改善的物理或生物学特性。在这项工作中，使用密度泛函理论，从与DNA损伤相关的三个方面，即去质子化，H吸收和H自由基加成，研究了这些人工DNA碱基对的稳定性。由于C8氧化鸟嘌呤（G）是DNA损伤的最重要产物之一，因此研究了尺寸扩展对C8活性的影响。计算结果表明，在G中插入芳族间隔环会大大降低C8位上的电子密度，从而导致更容易的去质子化或从C8位上吸氢，并在C8位上产生更难的ft自由基攻击。然而，如果间隔环是抗芳族的，则会观察到相反的现象，这是因为在C8位上电子密度增加。此外，间隔环的芳香性或抗芳香性越大，这些作用越显着。使用自然键轨道（NBO）和原子核的独立于核的化学位移（NICS）指数进行的进一步分析表明，电子分布在整个C8位点的出现是因为参与共轭结构的芳族间隔环增加了电子从富电子的咪唑环到变径六元环的离域，而抗芳族间隔环充当了一个供电子基团，不仅抑制了上述反应电子离域，但也会稍微增加C8位置上的电子密度。这些大小扩展的碱基对在不同的DNA破坏的环境中提高的稳定性可能会鼓励它们在实际应用中的使用。

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