The Influence of Clustered DNA Damage Containing Iz/Oz and OXO dG on the Charge Transfer through the Double Helix: A Theoretical Study.

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 ( OXO dG) 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[A 1 Iz 2 A 3 OXO G 4 A 5 ]*d[T 5 C 4 T 3 C 2 T 1 ], and oligo-Oz , d[A 1 Oz 2 A 3 OXO G 4 A 5 ]*d[T 5 C 4 T 3 C 2 T 1 ], 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, OXO dG 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 Oz 2 to complementary C 4 was noted during vertical to adiabatic anion relaxation, while for oligo-Iz , it was settled exclusively on the Iz 2 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 sp 2 or sp 3 . The above can confuse the single DNA damage recognition and removal processes, cause an increase in mutagenesis, and harm the effectiveness of anticancer therapy.