Cation-π interactions: computational analyses of the aromatic box motif and the fluorination strategy for experimental evaluation.
Cation-π interactions: computational analyses of the aromatic box motif and the fluorination strategy for experimental evaluation.
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DOI：
10.1039/c5cp04668h
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发表时间：
2015-11-21
期刊：
影响因子：
--
通讯作者：
Dougherty DA
中科院分区：
文献类型：
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作者：
Davis MR;Dougherty DA
阳离子-π相互作用在生物体系中很常见，许多结构研究表明芳香盒是一个常见的基序。为了了解芳香盒的性质，评估了几种计算方法再现实验阳离子-π结合能的能力。我们发现，在所测试的几种方法中，具有6-31G(d，p)基组的DFT方法M06的性能最好。研究了苯与几种不同阳离子(钠、钾、铵、四甲基铵和胍)的结合。此外，还研究了有机阳离子NH4+和NMe4+与从头算生成的芳香盒的结合，以及蛋白质晶体结构芳香盒的例子。这些数据，以及对阳离子-π相互作用的距离依赖性的研究表明，多个芳香族残基可以有效地促进阳离子结合，即使与最佳阳离子-π相互作用的位移超过一埃。我们还研究了苯和吲哚的渐进式氟化反应，并用得到的结合能重申了在体内研究阳离子-π相互作用的“氟化策略”的有效性。
Cation-π interactions are common in biological systems, and many structural studies have revealed the aromatic box as a common motif. With the aim of understanding the nature of the aromatic box, several computational methods were evaluated for their ability to reproduce experimental cation-π binding energies. We find the DFT method M06 with the 6-31G(d,p) basis set performs best of several methods tested. The binding of benzene to a number of different cations (sodium, potassium, ammonium, tetramethylammonium, and guanidinium) was studied. In addition, the binding of the organic cations NH4+ and NMe4+ to ab initio generated aromatic boxes as well as examples of aromatic boxes from protein crystal structures were investigated. These data, along with a study of the distance dependence of the cation-π interaction, indicate that multiple aromatic residues can meaningfully contribute to cation binding, even with displacements of more than an angstrom from the optimal cation-π interaction. Progressive fluorination of benzene and indole was studied as well, and binding energies obtained were used to reaffirm the validity of the “fluorination strategy” to study cation-π interactions in vivo.