Nuclear Coupled Electronic States Analyses Expose Nuclear Quantum Effects in Nucleobase Pairs

Tautomerization by double proton transfer of nucleobase pairs leads to point mutations of nucleic acids. A series of constrained nuclear-electronic orbital calculations, combined with natural bond orbital and kinetic analyses, has quantitatively revealed the importance of nuclear quantum effects in the reaction. Compared to the case where the nuclei are treated classically, the probability of the formation of the tautomeric isomers of Cytosine-Guanine, explicitly taking into account the NQEs, increased by a factor of 8.0 in the gas phase and by a factor of 20.5 in water. This could be explained by the increase in the number of electrons occupying the reaction site’s antibonding orbitals. The proportion of Cytosine-Guanine tautomeric isomers formed by double proton transfer was estimated to be 246 pairs per human genome.