The 2Ih and G Proximity Consequences on Charge Transfer through -DNA: Theoretical Studies of Clustered DNA Damage.

Genetic information is continuously exposed to harmful factors, both intra- and extracellular. Their activity can lead to the formation of different types of DNA damage. Clustered lesions (CDL) are problematic for DNA repair systems. In this study, the short ds-oligos with a CDL containing () or () 2Ih and G in their structure were chosen as the most frequent in vitro lesions. In the condensed phase, the spatial structure was optimized at the M062x/D95**:M026x/sto-3G level of theory, while the electronic properties were optimized at the M062x/6-31++G** level. The influence of equilibrated and non-equilibrated solvent-solute interactions was then discussed. It was found that the presence of ()2Ih in the ds-oligo structure causes a greater increase in structure sensitivity towards charge adoption than ()2Ih, while G shows high stability. Moreover, the analysis of charge and spin distribution reveals the different effects of 2Ih diastereomers. Additionally, the adiabatic ionization potential was found as follows for ()-2Ih and ()-2Ih in eV: 7.02 and 6.94. This was in good agreement with the AIP of the investigated ds-oligos. It was found that the presence of ()-2Ih has a negative influence on excess electron migration through ds-DNA. Finally, according to the Marcus theory, the charge transfer constant was calculated. The results presented in the article show that both diastereomers of 5-carboxamido-5-formamido-2-iminohydantoin should play a significant role in the CDL recognition process via electron transfer. Moreover, it should be pointed out that even though the cellular level of ( and )-2Ih has been obscured, their mutagenic potential should be at the same level as other similar guanine lesions found in different cancer cells.