Due to the lower redox potential comparing with guanine, it is the 8-azaguanine (8-AG) as the hole trap to form 8-azaguanine radical cation (8-AG^·+) after one-electron oxidation of DNA containing 8-azaguanine. In generally, the 8-AG^·+ may suffer from deprotonation to generate 8-AG(-H)·. In this text, we were stimulated to investigate the deprotonation reaction of 8-AG^·+ generating by one-electron oxidation at M06-2X/6-31+G(d) level with explicit water molecules and polarized continuum model (PCM) to simulate the solvent effect. By building deprotonation model with different number of explicit water molecules, we found that these four water molecules locating around N(1)-H, O(6), N(2)-H of 8-AG^·+ as well as the one locating in the second water shell which was hydrogen-bonding with the water around O(6) were necessary. If the water in the second water shell was not included, the imino proton (N(1)-H) would not transfer into the bulk water. In parallel, the N(1)-H would transfer to the O(6) of 8-AG^·+ by intramolecular proton transfer. If the water molecule locating around N(2)-H was removed, the 8-AG^·+ deprotonation would continue but the energy barrier would be lowered from 24.8 kJ/mol to 16.3 kJ/mol. In addition, the site of the water molecule in the second water shell was also studied. If putting the water in the second water shell around N(2)-H of 8-AG^·+, the proton would be stabilized between the N(1) of 8-AG^·+ and the oxygen of water molecule around N(1)-H meaning the proton would not be transferred into bulk water. Further, in order to test the influence of water number on 8-AG^·+ deprotonation, the fifth water molecule, which is hydrogen-bonding with the water molecule around N(2)-H and another N(2)-H, was added. The potential energy surface with 5H₂O revealed that it is almost no effect on the deprotonation pathway and energy barrier (25.5 kJ/mol). Lastly, so as to obtain the exact energy barrier of 8-AG^·+ deprotonation, the deprotonation model with more explicit water molecules (9H₂O) was proposed, where the additional water molecules were placed around N(2)-H, N(3), O(6), N(7) and N(8). From the potential energy surface, the deprotonation energy barrier of 8-AG^·+ was confirmed to be 19.5 kJ/mol. These theoretical results provide valuable dynamics information and mechanistic insights for further understanding the properties of nucleic acid base analogues and one-electron oxidation of DNA.

Key words: 8-azaguanine, one-electron oxidation, deprotonation reaction, potential energy surface