Anion Transporters Based on Noncovalent Balance including Anion-π, Hydrogen, and Halogen Bonding
Anion Transporters Based on Noncovalent Balance including Anion-π, Hydrogen, and Halogen Bonding
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基于非共价平衡的阴离子转运蛋白，包括阴离子键、氢键和卤素键
DOI：
10.1021/acs.joc.9b00561
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发表时间：
2019-07-19
影响因子：
3.6
通讯作者：
Wang, De-Xian
中科院分区：
文献类型：
--
作者：
Huang, Wen-Long;Wang, Xu-Dong;Wang, De-Xian
由新型非共价相互作用介导的阴离子跨膜转运是超分子化学的研究热点。本工作以没食子酸酯类化合物和一、二卤代三氮杂环化合物为原料，采用一锅法合成了一系列含有阴离子-pi-、氢-和卤素键位的恶杂杯[2]芳烃类转运体1和2。核磁共振氢谱显示1和2与溶液中的氯和溴有效结合，结合常数在10(2)-10(4)M-1范围内。通过两个络合物的单晶结构和密度泛函理论计算，揭示了阴离子-pi、氢键和卤素键的协同作用是阴离子结合的驱动力。荧光分析表明，化合物1是有效的氯离子转运体，其有效浓度(EC50)为3.17.4µM，大小顺序为1a>；1b>；1c>；1d。讨论了卤素键和协同非共价键对离子输运的贡献。值得注意的是，转运蛋白1具有很高的抗癌活性。在1和KCl60 mM存在下，HCT116细胞存活率降至11.924.9%，IC50值在52.366.4mM范围内。
Anion transmembrane transport mediated by novel noncovalent interactions is of central interest in supramolecular chemistry. In this work, a series of oxacalix[2]arene[2]triazine-derived transporters 1 and 2 bearing anion-pi-, hydrogen-, and halogen-bonding sites in rational proximity were designed and synthesized by a one-pot strategy starting from gallic acid ester derivatives and mono- or di-halogen-substituted triazines. 1H NMR titrations demonstrated efficient binding of 1 and 2 toward Cl and Br in solution, giving association constants in the range of 10(2)-10(4) M-1. Cooperation of anion-pi, hydrogen, and halogen bonding was revealed as a driving force for anion binding by single-crystal structures of two complexes and density functional theory calculations. Fluorescence assays indicated that compounds 1 are efficient chloride transporters with effective concentrations (EC50) falling in the range of 3.17.4 mu M and following an order of 1a > 1b > 1c > 1d. The contribution of halogen bonding and cooperative noncovalent bonds to ion transport was then discussed. Significantly, transporters 1 exhibit high anticancer activity. In the presence of 1 and KCl (60 mM), the cell survival of HCT116 reduces to 11.924.9% with IC50 values in the range of 52.366.4 mu M