Enol Tautomers of Watson−Crick Base Pair Models Are Metastable Because of Nuclear Quantum Effects

Intermolecular enol tautomers of Watson−Crick base pairs could emerge spontaneously via interbase double proton transfer. It has been hypothesized that their formation could be facilitated by thermal fluctuations and proton tunneling, and possibly be relevant to DNA damage. Theoretical and computational studies, assuming classical nuclei, have confirmed the dynamic stability of these rare tautomers. However, by accounting for nuclear quantum effects explicitly through Car−Parrinello path integral molecular dynamics calculations, we find the tautomeric enol form to be dynamically metastable, with lifetimes too insignificant to be implicated in DNA damage.

沃森-克里克碱基对（Watson−Crick base pairs）的分子间烯醇式互变异构体可通过碱基间双质子转移自发产生。已有假说提出，这类互变异构体的形成可受热涨落与质子隧穿效应促进，且可能与DNA损伤相关。假定原子核为经典粒子的理论与计算研究，已证实这类稀有互变异构体的动态稳定性。然而，通过卡-帕里内罗路径积分分子动力学（Car−Parrinello path integral molecular dynamics）计算显式考虑核量子效应后，我们发现该烯醇式互变异构体仅为动态亚稳态，其寿命极短，不足以参与DNA损伤过程。