The Influence of Oxidized Imino-Allantoin in the Presence of [sup.OXO]G on Double Helix Charge Transfer: A Theoretical Approach

The genome is continuously exposed to a variety of harmful factors that result in a significant amount of DNA damage. This article examines the influence of a multi-damage site containing oxidized imino-allantoin ([sup.OX]Ia) and 7,8-dihydro-8-oxo-2′-deoxyguanosine ([sup.OXO]dG) on the spatial geometry, electronic properties, and ds-DNA charge transfer. The ground stage of a d[A[sub.1] [sup.OX]Ia[sub.2]A[sub.3] [sup.OXO]G[sub.4]A[sub.5]]*d[T[sub.5]C[sub.4]T[sub.3]C[sub.2]T[sub.1]] structure was obtained at the M06-2X/6-D95**//M06-2X/sto-3G level of theory in the condensed phase, with the energies obtained at the M06-2X/6-31++G** level. The non-equilibrated and equilibrated solvent-solute interactions were also considered. Theoretical studies reveal that the radical cation prefers to settle on the [sup.OXO]G moiety, irrespective of the presence of [sup.OX]Ia in a ds-oligo. The lowest vertical and adiabatic ionization potential values were found for the [sup.OXO]G:::C base pair (5.94 and 5.52 [eV], respectively). Conversely, the highest vertical and adiabatic electron affinity was assigned for [sup.OX]IaC as follows: 3.15 and 3.49 [eV]. The charge transfers were analyzed according to Marcus’ theory. The highest value of charge transfer rate constant for hole and excess electron migration was found for the process towards the [sup.OXO]GC moiety. Surprisingly, the values obtained for the driving force and activation energy of electro-transfer towards [sup.OX]Ia[sub.2]C[sub.4] located this process in the Marcus inverted region, which is thermodynamically unfavorable. Therefore, the presence of [sup.OX]Ia can slow down the recognition and removal processes of other DNA lesions. However, with regard to anticancer therapy (radio/chemo), the presence of [sup.OX]Ia in the structure of clustered DNA damage can result in improved cancer treatment outcomes.