PDF(Pubmed)
Abstract：
The genome-the source of life and platform of evolution-is continuously exposed to harmful factors, both extra- and intra-cellular. Their activity causes different types of DNA damage, with approximately 80 different types of lesions having been identified so far. In this paper, the influence of a clustered DNA damage site containing imidazolone (Iz) or oxazolone (Oz) and 7,8-dihydro-8-oxo-2\'-deoxyguanosine (OXOdG) on the charge transfer through the double helix as well as their electronic properties were investigated. To this end, the structures of oligo-Iz, d[A1Iz2A3OXOG4A5]*d[T5C4T3C2T1], and oligo-Oz, d[A1Oz2A3OXOG4A5]*d[T5C4T3C2T1], were optimized at the M06-2X/6-D95**//M06-2X/sto-3G level of theory in the aqueous phase using the ONIOM methodology; all the discussed energies were obtained at the M06-2X/6-31++G** level of theory. The non-equilibrated and equilibrated solvent-solute interactions were taken into consideration. The following results were found: (A) In all the discussed cases, OXOdG showed a higher predisposition to radical cation formation, and B) the excess electron migration toward Iz and Oz was preferred. However, in the case of oligo-Oz, the electron transfer from Oz2 to complementary C4 was noted during vertical to adiabatic anion relaxation, while for oligo-Iz, it was settled exclusively on the Iz2 moiety. The above was reflected in the charge transfer rate constant, vertical/adiabatic ionization potential, and electron affinity energy values, as well as the charge and spin distribution. It can be postulated that imidazolone moiety formation within the CDL ds-oligo structure and its conversion to oxazolone can significantly influence the charge migration process, depending on the C2 carbon hybridization sp2 or sp3. The above can confuse the single DNA damage recognition and removal processes, cause an increase in mutagenesis, and harm the effectiveness of anticancer therapy.
摘要：
基因组——生命之源和进化平台——不断暴露于有害因素，细胞外和细胞内。它们的活动会导致不同类型的DNA损伤，到目前为止，已经确定了大约80种不同类型的病变。在本文中,研究了含有咪唑酮（Iz）或恶唑酮（Oz）和7,8-二氢-8-氧代-2'-脱氧鸟苷（OXOdG）的簇状DNA损伤位点对通过双螺旋的电荷转移及其电子性质的影响。为此,oligo-Iz的结构,d[A1Iz2A3OXOG4A5]*d[T5C4T3C2T1],和寡核苷酸-Oz,d[A1Oz2A3OXOG4A5]*d[T5C4T3C2T1],使用ONIOM方法在水相中的理论的M06-2X/6-D95**/M06-2X/sto-3G水平下进行了优化；所有讨论的能量均在理论的M06-2X/6-31G**水平下获得。考虑了非平衡和平衡的溶剂-溶质相互作用。发现以下结果：（A）在所有讨论的情况下，OXOdG显示出更高的自由基阳离子形成倾向，和B)朝向Iz和Oz的过量电子迁移是优选的。然而,在oligo-Oz的情况下,在垂直绝热阴离子弛豫过程中，注意到从Oz2到互补C4的电子转移，而对于oligo-Iz,它只固定在Iz2部分上。上述内容反映在电荷转移速率常数中，垂直/绝热电离电势,和电子亲和能量值，以及电荷和自旋分布。可以推测，CDLds-oligo结构中咪唑酮部分的形成及其向恶唑酮的转化可以显着影响电荷迁移过程，取决于C2碳杂交sp2或sp3。以上可以混淆单个DNA损伤识别和去除过程，导致诱变增加，并损害抗癌治疗的有效性。
