Noncanonical Isomers of Nucleoside Cation Radicals: An Ab Initio Study of the Dark Matter of DNA Ionization.

ABSTRACT

Cation radicals of DNA nucleosides, 2'-deoxyadenosine, 2'-deoxyguanosine, 2'-deoxycytidine, and 2'-deoxythymidine, can exist in standard canonical forms or as noncanonical isomers in which the charge is introduced by protonation of the nucleobase, whereas the radical predominantly resides in the deoxyribose moiety. Density functional theory as well as correlated ab initio calculations with coupled clusters (CCSD(T)) that were extrapolated to the complete basis set limit showed that noncanonical nucleoside ion isomers were thermodynamically more stable than their canonical forms in both the gas phase and as water-solvated ions. This indicated the possibility of exothermic conversion of canonical to noncanonical forms. The noncanonical isomers were calculated to have very low adiabatic ion-electron recombination energies (REad) for the lowest-energy isomers 2'-deoxy-(N-3H)adenos-1'-yl (4.74 eV), 2'-deoxy-(N-7H)guanos-1'-yl (4.66 eV), 2'-deoxy-(N-3H)cytid-1'-yl (5.12 eV), and 2'-deoxy-5-methylene-(O-2H)uridine (5.24 eV). These were substantially lower than the REad value calculated for the canonical 2'-deoxyadenosine, 2'-deoxy guanosine, 2'-deoxy cytidine, and 2'-deoxy thymidine cation radicals, which were 7.82, 7.46, 8.14, and 8.20 eV, respectively, for the lowest-energy ion conformers of each type. Charge and spin distributions in noncovalent cation-radical dA⊂dT and dG⊂dC nucleoside pairs and dAT, dCT, dTC, and dGC dinucleotides were analyzed to elucidate the electronic structure of the cation radicals. Born-Oppenheimer molecular dynamics trajectory calculations of the dinucleotides and nucleoside pairs indicated rapid exothermic proton transfer from noncanonical T+· to A in both dAT+· and dA⊂dT+·, leading to charge and radical separation. Noncanonical T+· in dCT+· and dTC+· initiated rapid proton transfer to cytosine, whereas the canonical dCT+· dinucleotide ion retained the cation radical structure without isomerization. No spontaneous proton transfer was found in dGC+· and dG⊂dC+· containing canonical neutral and noncanonical ionized deoxycytidine.