基于传导性的DNA碱基修饰及其结构性质探索

The design of new DNA motifs has shown great potential application value in the expansion of the genetic alphabet, the design of DNA molecular probe, the synthesis of DNA molecular wires and others. Therefore, there has been a rapidly increasing amount of research into designing modified versions of DNA over the past several decades. Based on the design of conductive DNA bases, this project tries to establish an effective base modification program. The relevant structural and electronic properties are investigated by means of quantum calculations and molecular dynamics simulations. All the modified bases form base pairs specifically with their natural counterparts and assemble duplex helices. The corresponding structural and electronic properties, oxidative damage, free radicals generated and charge holes along the chain transfer mechanism are discussed under the different ways of modification and environmental factors. We will try to build modified structure-activity relationship between the structure and functional properties. The research of this project is of great significance that can reveal the difference of the natural and modified DNA, as well as it can provide important information about the synthesis of DNA molecular wire and molecular devices.

鉴于DNA修饰在扩展遗传字母表、设计DNA分子探针、合成DNA分子导线等方面所表现出的潜在的应用价值，DNA修饰多年来一直是国际上关注的焦点课题。围绕传导性DNA碱基修饰的相关问题，本项目试图建立有效的碱基修饰方案。用量子理论方法深入研究修饰碱基的结构性质和电子性质等，并构建以修饰碱基为基本结构单元的修饰DNA螺旋链，对比天然DNA，探讨修饰方式和环境因素对修饰DNA的结构及电子性质、氧化损伤、生成自由基及电荷空穴沿链迁移机制的影响。试图建立修饰结构与功能性质之间的构效关系。本工作对揭示天然及修饰DNA的异同性等具有重要意义，同时对合成DNA基分子导线、荧光探针等分子器件设计也提供重要信息。

围绕传导性DNA碱基修饰的相关问题，采用密度泛函理论计算研究了不同的稱合模式包括WC氧键模式、Hoogsteen模式、小沟处氢键模式和堆积模式下双氧化的AT碱基对的结构和电子性质。采用对称性破缺(BS)的非限制性方法揭示了双自由基分子的电磁相互作用。双电子电离很大程度上降低了碱基对AT的稳定性，从而导致了一种意想不到的具有负解离能的解离通道，同时由于势垒的阻碍，化合物不会自动解离，从而能够暂时稳定存在。这种解离通道是由静电排斥和氢键吸引力这两种相互作用之间的平衡决定的。研究了双电子氧化Watson-Crick模式的AT碱基对，计算了每一个可能的质子转移途径。结果显示不仅存在双质子转移过程，而且还是一个两步转移过程。在理论上预测了许多双氧化的AT碱基对具有双自由基特性，并且这些双自由基碱基对表现出了一定程度的铁磁性和反铁磁性，这些磁性取决于不同的结合位点和碱基类型。本工作对揭示天然及修饰DNA的异同性等具有重要意义，同时对合成DNA基分子导线、荧光探针等分子器件设计也提供重要信息。