氢键型人工碱基对P-Z的光化学稳定性的理论研究

Unnatural base pair P-Z with hydrogen bonds is very similar with natural base pair G-C in structure and stability, and has the expected characteristics of natural base. Thus P-Z is expected to expand the storage of genetic information, and even to be used in semi-synthetic organism, new protein, and new biological field. However, P(Z) base can be excited by absorbing ultraviolet photons, which could induce a series of photochemical reactions. It is not clear whether P(Z) monomer and P-Z dimer have fast internal conversion channels as natural base pairs. Therefore, it is particularly necessary to study their photochemical stability. In this project, we study the excited state reaction dynamics of P(Z) monomer and P-Z dimer using computational method at the CASPT2/CASSCF level. Firstly, we investigate the feasibility of various internal conversions to clarify the decay mechanism and photostability of monomers P and Z. Secondly, we investigate the proton transfer mechanism by constructing two-dimensional potential energy surfaces including all single and double proton transfer processes in the dimer to clear the photostability. Finally, we also study the effect of nitro group on the excited state proton transfer mechanism by studying proton transfer behavior in the P-Z dimers with nitro group in different positions. This project is expected to expand the composition of DNA base, and provides a solid theoretical basis for synthetic biology and the mechanism of DNA damage and repair.

氢键型人工碱基对P-Z在结构和稳定性上与自然碱基对G-C相似，并具有自然碱基的预期特征，有望扩大遗传信息的存储，甚至用于半合成器官和新生物领域。然而P、Z碱基易吸收紫外光子，产生电子激发态，进而可诱发一系列光化学反应。P、Z单体和P-Z二体能否像自然碱基（对）一样具有快速的去激发反应路径这一问题尚不清晰。本项目利用量子化学手段在CASPT2/CASSCF水平下对P、Z单体和P-Z二体的激发态光反应过程进行研究。通过考察P、Z单体中可能存在的各种内转换通道，阐明单体的激发态衰减机理，明确其光化学稳定性；通过构建二维激发态势能面研究二体中所有单质子、双质子转移过程，进而揭示质子转移在P-Z二体光稳定性中的作用；通过比较研究不同位置硝基化的P-Z二体激发态质子转移行为，总结硝基化对二体光化学稳定性影响的规律。本课题有望拓展DNA碱基组成、为合成生物学和DNA损伤及修复机理提供坚实的理论依据。

氢键型人工碱基对P-Z在结构和稳定性上与自然碱基对G-C相似，并具有自然碱基的预期特征，有望扩大遗传信息的存储，甚至用于半合成器官和新生物领域。DNA的光稳定性对生物体的正常功能具有重要意义。P-Z是一种氢键人工DNA碱基对，其中P和Z分别代表2-氨基咪唑[1,2-a]-1,3,5-三嗪-4（8H）酮和6-氨基-5-硝基-2（1H）-吡啶酮。采用静态TDDFT计算及RICC2计算结合TDDFT水平上的非绝热动力学模拟方法，研究了P-Z对的激发态弛豫机制。揭示了硝基旋转、硝基平面外变形和氢键单质子转移（SPT）的作用。势能曲线的计算结果表明，沿着氢键的SPT过程不利于静态发生，这与自然碱基对的单质子转移形成了鲜明的对比。非绝热动力学模拟表明，激发态硝基旋转和硝基面外形变是导致快速内转换的两个重要弛豫通道。动力学结果还观察到从Z到P的SPT，随后在P上发生畸变，导致快速的内转换。然而，这种通道（通过SPT过程衰减）在统计上对激发态弛豫机制起次要作用。这项工作揭示了天然碱基对和人工碱基对激发态弛豫机制的巨大差异，也为氢键和硝基在P-Z碱基对中的作用提供了新的线索。