Beijing National Laboratory for Molecular Sciences (BNLMS), Institute of Chemistry, Chinese Academy of Sciences , Beijing 100190, China.
J Am Chem Soc. 2015 Jan 14;137(1):259-66. doi: 10.1021/ja510285t. Epub 2014 Dec 30.
Although numerous studies have been devoted to the charge transfer through double-stranded DNA (dsDNA), one of the major problems that hinder their potential applications in molecular electronics is the fast deprotonation of guanine cation (G(+•)) to form a neutral radical that can cause the termination of hole transfer. It is thus of critical importance to explore other DNA structures, among which G-quadruplexes are an emerging topic. By nanosecond laser flash photolysis, we report here the direct observation and findings of the unusual deprotonation behavior (loss of amino proton N2-H instead of imino proton N1-H) and slower (1-2 orders of magnitude) deprotonation rate of G(+•) within G-quadruplexes, compared to the case in the free base dG or dsDNA. Four G-quadruplexes AG3(T2AG3)3, (G4T4G4)2, (TG4T)4, and G2T2G2TGTG2T2G2 (TBA) are measured systematically to examine the relationship of deprotonation with the hydrogen-bonding surroundings. Combined with in depth kinetic isotope experiments and pKa analysis, mechanistic insights have been further achieved, showing that it should be the non-hydrogen-bonded free proton to be released during deprotonation in G-quadruplexes, which is the N2-H exposed to solvent for G bases in G-quartets or the free N1-H for G base in the loop. The slower N2-H deprotonation rate can thus ensure less interruption of the hole transfer. The unique deprotonation features observed here for G-quadruplexes open possibilities for their interesting applications as molecular electronic devices, while the elucidated mechanisms can provide illuminations for the rational design of G-quadruplex structures toward such applications and enrich the fundamental understandings of DNA radical chemistry.
尽管已经有许多研究致力于双链 DNA（dsDNA）中的电荷转移，但阻碍其在分子电子学中潜在应用的一个主要问题是鸟嘌呤阳离子（G(+•)）的快速去质子化，形成中性自由基，从而导致空穴转移的终止。因此，探索其他 DNA 结构至关重要，其中 G-四链体是一个新兴的研究课题。通过纳秒激光闪光光解，我们在这里直接观察到并发现了 G-四链体中 G(+•)的异常去质子化行为（失去氨基质子 N2-H，而不是亚氨基质子 N1-H）和更慢的（1-2 个数量级）去质子化速率，与游离碱基 dG 或 dsDNA 的情况相比。我们系统地测量了四个 G-四链体 AG3(T2AG3)3、(G4T4G4)2、(TG4T)4 和 G2T2G2TGTG2T2G2(TBA)，以研究去质子化与氢键环境的关系。结合深入的动力学同位素实验和 pKa 分析，进一步获得了机制见解，表明在 G-四链体中去质子化时应该释放的是非氢键结合的游离质子，这是 G-四联体中 G 碱基的 N2-H 暴露于溶剂或环中的游离 N1-H 用于 G 碱基。因此，较慢的 N2-H 去质子化速率可以确保空穴转移的中断较少。这里观察到的 G-四链体独特的去质子化特征为它们作为分子电子器件的有趣应用开辟了可能性，而阐明的机制可以为 G-四链体结构的合理设计提供启示，以实现这些应用，并丰富 DNA 自由基化学的基本认识。
