Electron and Hole Interactions with P, Z, and P:Z and the Formations of Mutagenic Products by Proton Transfer Reactions
P and Z are recently identified as promiscuous artificial nucleobases, which can behave as G and C respectively in the duplex DNA. These nucleobases have been shown to participate in the replication reaction and can form stable B-DNA. A short sequence of DNA containing P and Z has also been shown to help in the diagnosis of diseases. However, the behavior of P and Z exposed to radiation has not been explored. As electrons and holes are created during the interaction of radiation with DNA bases, it is desirable to understand the electron or hole trapping abilities of P and Z in the duplex DNA. To unravel these, electron affinities (EA) and ionization potentials (IP) of P and Z in bare and microhydrated complexes are computed and compared with those of G and C by using the B3LYP-D3 dispersion-corrected density functional theoretical method and the IEFPCM method to account for the bulk solvation in water. The computed EA and IP values of P and Z are found to be large positive and hence their anions (P.- and Z.-) and cations (P.+ and Z.+) would be stable in DNA. It is further found that the electron trapping ability of Z is significantly higher than that of P, G, and C. However, the hole trapping ability of P is slightly higher than that of Z but less than that of G. To account for the proton transfer abilities of Z, Z.+, and Z.-, stabilities of different proton transferred products and their tautomers are also explored. It is found that among the different products, the one formed by the transfer of the N3 proton would be the most stable. However, the N3 proton transfer from Z to P in the P:Z and P:Z.- complexes would be unfeasible due to high barrier and endothermic nature of the reaction. Remarkably, the same reaction in the P:Z.+ complex is found to be exothermic with low barrier energy. Hence, the conversion of Z to Z.+ would facilitate the N3 proton transfer from Z to P in the P:Z complex. As the proton transferred products were suggested to induce genetic mutations, we propose that the formations of Z(N3-H). and P(N1+H)+ in DNA would be mutagenic. These results are expected to help in the understanding of the radiation biology of P and Z in the single-stranded and double-stranded DNA.