Fluorinated DNA bases as probes of electrostatic effects in DNA base stacking
Fluorinated DNA bases as probes of electrostatic effects in DNA base stacking
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DOI：
10.1002/anie.200352531
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发表时间：
2003-01-01
影响因子：
16.6
通讯作者：
Kool, ET
中科院分区：
文献类型：
--
作者：
Lai, JS;Qu, J;Kool, ET
非共价相互作用对天然DNA和修饰DNA热力学稳定性的影响是近年来研究的热点。空间位阻、堆积、氢键和小沟溶剂化的影响被认为是促成因素。[1-4]螺旋DNA中的主要稳定因素可能是碱基堆积。[5，6]为了探索有助于这种堆积在水中稳定性的物理因素，已经研究了天然和非天然取代的短DNA寡聚体的测量解链数据。[5，7，8]这些实验表明，范德华力和疏溶剂力可能是堆叠稳定的重要贡献者。除此之外，理论工作已经指出了静电相互作用在DNA中堆叠碱基的稳定性和优选几何形状中的可能重要性。[9-14]了解这些问题可以更好地设计修饰的DNA，但相对较少的实验信息是关于这些静电因素。有充分的证据表明，芳香环可以在某些环境中表现出显着的偶极和四极静电相互作用。在非极性溶剂中使用含有各种供电子和吸电子取代基的芳香族化合物的研究已经证明了堆叠能量和几何形状的显着静电效应。[15-17]尽管在含水体系中静电偶极效应大大减弱，但局部静电效应仍然被认为在控制DNA中相邻碱基对几何形状方面发挥作用。[6，12]对水中小分子模型系统的研究表明，静电效应相对较弱，分散效应是控制堆积稳定性的主要因素。[18在这种模型系统中的疏水效应似乎只起很小的作用，尽管这个问题一直存在争议。[18四极相互作用也已经在特殊情况下被记录;例如，苯能够与含有正电荷的分子静电相互作用，如通过充分记录的阳离子-π相互作用所证明的，甚至在水性系统中。[22]相比之下，全氟苯，其相反的四极符号，可以堆叠以及（在低极性环境中）与富电子芳环。[23]最近的一项计算研究也显示了水与苯和全氟苯相互作用的配位作用。[24]虽然苯-，[25] 2，4-二氟苯-，[26] 2，4，5-三氟苯-，[26]和五氟苯取代的[27]脱氧核糖核苷和4-单氟苯核糖核苷[28]以前已经描述过，但没有关于它们相对堆积能力的信息，也没有关于它们与不同相邻DNA碱基相互作用的任何数据。
The noncovalent interactions affecting the thermodynamic stability of natural and modified DNA have been topics of broad interest in recent years. The effects of sterics, stacking, hydrogen bonding, and minor-groove solvation have been considered as contributing factors.[1–4] Probably the dominant stabilizing factor in helical DNA is base stacking.[5, 6] In order to probe the physical factors that contribute to the stability of this stacking in water, measured melting data of short DNA oligomers, both naturally and nonnaturally substituted, has been studied.[5, 7, 8] Such experiments have suggested that vanderWaals and solvophobic forces can be important contributors to the stabilization of stacking. Beyond this, theoretical work has pointed out the possible importance of electrostatic interactions in the stability and preferred geometry of stacked bases in DNA.[9–14] Understanding these issues could allow for better design of modified DNAs, but relatively little experimental information is available on such electrostatic factors.It is well documented that aromatic rings can exhibit significant dipolar and quadrupolar electrostatic interactions in certain environments. Studies in nonpolar solvents using aromatic compounds containing various electron-donating and-withdrawing substituents have demonstrated significant electrostatic effects in stacking energetics and geometries.[15–17] Although in aqueous systems the electrostatic dipole effects are greatly diminished, localized electrostatic effects are still believed to play a role in governing neighboring base-pair geometries in DNA.[6, 12] Studies with smallmolecule model systems in water have suggested that electrostatic effects are relatively weak, and that dispersive effects are a major factor governing stacking stability.[18, 19] Hydrophobic effects in such model systems appear to play only a small role, although this issue has been debated.[18, 20, 21] Quadrupolar interactions have also been documented in specialized cases; for example, benzene is capable of electrostatic interactions with molecules containing a positive charge, as demonstrated by well-documented cation–π interactions, even in aqueous systems.[22] By contrast, perfluorobenzene, with its opposite quadrupolar sign, can stack well (in low polarity environments) with electron-rich aromatic rings.[23] A recent computational study also showed the coordination by water in interactions with benzene and perfluorobenzene.[24] Although benzene-,[25] 2, 4-difluorobenzene-,[26] 2, 4, 5-trifluorobenzene-,[26] and pentafluorobenzenesubstituted [27] deoxyribonucleosides and 4-monofluorobenzene ribonucleoside [28] have been previously described, no information on their relative stacking abilities is available, nor is there any data on their interactions with varied neighboring DNA bases.