Francés-Monerris Antonio, Gattuso Hugo, Roca-Sanjuán Daniel, Tuñón Iñaki, Marazzi Marco, Dumont Elise, Monari Antonio
Université de Lorraine , CNRS , LPCT , Nancy F-54000 , France . Email:
Theoretical Physical Chemistry , Research Unit Molecular Systems (UR MOLSYS) , University of Liège , 4000 Liège , Belgium.
Chem Sci. 2018 Sep 18;9(41):7902-7911. doi: 10.1039/c8sc03252a. eCollection 2018 Nov 7.
The intrinsic photostability of nucleic acids is intimately related to evolution of life, while its understanding at the molecular and electronic levels remains a challenge for modern science. Among the different decay pathways proposed in the last two decades, the excited-state hydrogen transfer between guanine-cytosine base pairs has been identified as an efficient non-reactive channel to dissipate the excess of energy provided by light absorption. The present work studies the dynamics of such phenomena taking place in a (dG)·(dC) B-DNA homopolymer in water solution using state-of-the-art molecular modelling and simulation methods. A dynamic effect that boosts the photostability of the inter-strand hydrogen atom transfers, inherent to the Watson-Crick base pairing, is unveiled and ascribed to the energy released during the proton transfer step. Our results also reveal a novel mechanism of DNA decay named four proton transfer (FPT), in which two protons of two adjacent G-C base pairs are transferred to form a biradical zwitterionic intermediate. Decay of the latter intermediate to the ground state triggers the transfer of the protons back to the guanine molecules recovering the Watson-Crick structure of the tetramer. This FPT process is activated by the close interaction of a nearby Na counterion with the oxygen atoms of the guanine nucleobases and hence represents a photostable channel operative in natural nucleic acids.
核酸的内在光稳定性与生命的演化密切相关，然而在分子和电子层面上对其进行理解仍是现代科学面临的一项挑战。在过去二十年中提出的不同衰变途径中，鸟嘌呤 - 胞嘧啶碱基对之间的激发态氢转移已被确定为一种有效的非反应性通道，用于耗散光吸收所提供的多余能量。本研究使用最先进的分子建模和模拟方法，研究了在水溶液中的(dG)·(dC) B - DNA同聚物中发生的此类现象的动力学。揭示了一种增强链间氢原子转移光稳定性的动态效应，这种效应是沃森 - 克里克碱基对所固有的，并将其归因于质子转移步骤中释放的能量。我们的结果还揭示了一种名为四质子转移（FPT）的DNA衰变新机制，其中两个相邻G - C碱基对的两个质子被转移以形成双自由基两性离子中间体。后者中间体衰变至基态会触发质子回到鸟嘌呤分子，从而恢复四聚体的沃森 - 克里克结构。这种FPT过程是由附近的Na反离子与鸟嘌呤核碱基的氧原子紧密相互作用所激活的，因此代表了一种在天然核酸中起作用的光稳定通道。
