(Fapy)dG in the Shadow of (OXO)dG—A Theoretical Study of Clustered DNA Lesions

Genetic information, irrespective of cell type (normal or cancerous), is exposed to a range of harmful factors, which can lead to more than 80 different types of DNA damage. Of these, (oxo)G and (Fapy)G have been identified as the most abundant in normoxic and hypoxic conditions, respectively. This article considers d[A(Fapy)GA(OXO)GA]*[TCTCT] (oligo-(Fapy)G) with clustered DNA lesions (CDLs) containing both the above types of damage at the M06-2x/6-31++G** level of theory in the condensed phase. Furthermore, the electronic properties of oligo-(Fapy)G were analysed in both equilibrated and non-equilibrated solvation–solute interaction modes. The vertical/adiabatic ionization potential (VIP, AIP) and electron affinity (VEA, AEA) of the investigated ds-oligo were found as follows in [eV]: 5.87/5.39 and −1.41/−2.09, respectively. The optimization of the four ds-DNA spatial geometries revealed that the trans(Fapy)dG was energetically privileged. Additionally, CDLs were found to have little influence on the ds-oligo structure. Furthermore, for the (Fapy)GC base-pair isolated from the discussed ds-oligo, the ionization potential and electron affinity values were higher than those assigned to (OXO)GC. Finally, a comparison of the influence of (Fapy)GC and (OXO)GC on charge transfer revealed that, in contrast to the (OXO)GC base-pair, which, as expected, acted as a radical cation/anion sink in the oligo-(Fapy)G structure, (Fapy)GC did not significantly affect charge transfer (electron–hole and excess–electron). The results presented below indicate that 7,8-dihydro-8-oxo-2′-deoxyguanosine plays a significant role in charge transfer through ds-DNA containing CDL and indirectly has an influence on the DNA lesion recognition and repair process. In contrast, the electronic properties obtained for 2,6-diamino-4-hydroxy-5-foramido-2′deoxypyrimidine were found to be too weak to compete with (OXO)G to influence charge transfer through the discussed ds-DNA containing CDL. Because increases in multi-damage site formation are observed during radio- or chemotherapy, understanding their role in the above processes can be crucial for the efficiency and safety of medical cancer treatment.