Electronic insights into the role of nuclear quantum effects in proton transfer reactions of nucleobase pairs

Double proton transfer in nucleobase pairs leads to point mutations in nucleic acids. A series of constrained nuclear-electronic orbital calculations combined with natural bond orbital and non-covalent interaction analyses, and kinetic studies have quantitatively revealed the importance of nuclear quantum effects (NQEs) in the reaction. Compared with the classical treatment of the nuclei, the probability of forming the tautomeric isomers of Cytosine-Guanine, when explicitly accounting for NQEs, increased by a factor of 8.0. This outcome can be attributed to enhancing the interaction between the orbitals at the reactive site due to NQEs, which increased the number of electrons occupying the antibonding orbitals.