Juliana Gonçalves De Abrantes

This thesis focuses on the investigation of nuclear quantum effects (NQE) on DNA’s stability and photostability, by modulating proton transfer in guanine–cytosine (GC) nucleobases in different contexts.

First, the double-proton transfer between canonical and methylated GC base pairs is analysed under conditions relevant to DNA replication, explicitly including solvent effects and strand separation. By combining density functional theory (DFT) with a nuclear–electronic orbital description of the transferring protons, it is found that NQE significantly enhance proton transfer rates. For the canonical GC pair, the resulting populations of mutagenic species become comparable to spontaneous point-mutation rates in DNA.

Next, photoinduced proton transfer in stacked (GC)2 tetramers is investigated using nonadiabatic surface-hopping dynamics. The simulations reveal an intricate interplay between charge transfer and proton transfer, in which interstrand proton transfer from guanine to cytosine provides an efficient non-radiative decay channel back to the ground state, thereby contributing to DNA photostability.

Finally, NQE on the first excited-state (S1) potential energy surface of the GC base pair are evaluated by combining time-dependent DFT with the nuclear–electronic orbital framework. It is found that NQE strongly stabilise conical intersection structures, steepening the S1 surface along the proton-transfer coordinate. This indicates that NQE facilitate the access to non-radiative decay pathways without altering the proton-coupled electron-transfer mechanism, but assisting photostability mechanisms in DNA. Overall, these studies demonstrate that the quantum nature of the protons in GC hydrogen bonds can play a dual role: under replication conditions, it can increase mutagenic species formation, whereas under photoexcitation the NQE promote an efficient relaxation pathway that leads to DNA photostability.