TRANSITION METAL DNA COMPLEXES--INSULATORS OR WIRES

核酸的生物合成、遗传信息的调节和辐射损伤/修复通过电子转移(ET)反应进行，通常涉及过渡金属络合物[1-6]。这些系统中的ET发生在很远的距离上，远远超出了范德华接触的范围。基本的ET机制目前正在紧张的研究中，但仍然是实质性辩论的主题[7-10]。过去五年中报道的实验似乎发生了戏剧性的冲突[11-13]；最基本的问题仍然是，电子在连接到DNA的金属络合物之间移动的距离和速度有多远[14]。在这种情况下，理论可以通过描绘可触及的机械主义者政权，在解开表面上的冲突方面发挥特别重要的作用。更重要的是，理论可以帮助设计新的实验，这些实验将为所提出的电子转移机制提供关键测试。这项研究的目的是利用现代电子结构理论和分子动力学模拟方法来限制DNA中电子转移的距离和速度。这个项目的主要目标是：(1)确定当供体和受体的能级远离碱基对能级时，DNA电子转移速率对供体(D)和受体(A)氧化还原活性过渡金属基团和DNA序列的能级有多敏感；(2)当供体和受体的能级接近碱基对能级时，确定DNA电子转移率对供体和受体氧化还原活性过渡金属基团和DNA序列的能级有多敏感。(3)确定DNA三维结构(包括水合作用)中丰富的动力学涨落是如何调节供体-受体相互作用的。本项目将使用半经验[15]和线性标度从头算电子结构方法[16，17]来计算施主-受主电子相互作用。这些计算中使用的分子几何形状将从分子力学和经典分子动力学模拟中抽样。最后，将计算电子转移重组能[18-20]。综上所述，这三项研究将被用于建立DNA电子隧穿过程的综合理论，并将揭示DNA电子隧穿过程对给体/受体结合基序和能量学、DNA序列以及DNA结构的动态涨落的依赖性。

Nucleic acid biosynthesis, regulation of genetic information, and radiation damage/repair proceed via electron transfer (ET) reactions, often involving transition metal complexes [1-6]. ET in these systems occurs over large distances, well beyond van der Waals contact. The fundamental ET mechanism is under intense current investigation, but remains the subject of substantial debate [7-10]. Experiments reported in the last five years appear to be in dramatic conflict [11-13]; the most basic question of how far and how fast electrons can travel between metal complexes attached to DNA remains open [14]. In instances of this kind, theory can play a particularly important role in unraveling apparent conflicts by charting the accessible mechanist regimes. More importantly, theory can help design new experiments that will provide the critical tests of proposed electron transfer mechanisms. The goal of this study is to employ modern methods of electronic structure theory and molecular dynamics simulation to place constraints upon how far and how fast electron transfer may proceed in DNA. The critical aims of this project are: (1) to determine how sensitive DNA electron transfer rates are to the energetics of the donor (D) and acceptor (A) redox active transition-metal groups and DNA sequence when the energy levels of donor and acceptor are far from the energies of the base pair levels, (2) to determine how sensitive DNA electron transfer rates are to the energetics of the donor and acceptor redox active transition-metal groups and DNA sequence when the energy levels of donor and acceptor are close to the energies of the base pair levels, (3) to determine how the rich dynamical fluctuations in three-dimensional DNA structure (including hydration) modulate the donor-acceptor interaction. This project will employ both semi-empirical [15] and linear scaling ab initio electronic structure methods [16,17] to compute the donor- acceptor electronic interaction. Molecular geometries used in these calculations will be sampled from molecular mechanics and classical molecular dynamics simulations. Finally, electron transfer reorganization energies will be calculated [18-20]. Taken together, these three investigations will be used to build a comprehensive theory of DNA electron tunneling processes, and should reveal the dependence upon donor/acceptor binding motif and energetics, , DNA sequence, and the dynamical fluctuations of the DNA structure.