An Artificial Estrogen Receptor through Combinatorial Imprinting
An Artificial Estrogen Receptor through Combinatorial Imprinting
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DOI：
10.1002/chem.201201428
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发表时间：
2012-11-01
影响因子：
4.3
通讯作者：
Sellergren, Borje
中科院分区：
文献类型：
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作者：
Schillinger, Eric;Moeder, Monika;Sellergren, Borje
以17β-雌二醇(E_2)为模板，采用三元共聚印迹法制备了以干扰内分泌的雌激素活性化合物(EAC)为靶点的聚合物吸附材料。从一组代表Bronsted酸、碱、氢键供体和受体的8个功能单体以及pi相互作用的单体，制备了一个包含所有可能的功能单体的二元组合的三聚物库。结合测试表明，与非印迹聚合物(NIP)或使用单一功能单体制备的聚合物相比，印迹聚合物对E2的亲和力明显更高。甲基丙烯酸(MAA)和对乙烯基苯甲酸的组合提供了一种特别有前景的先导聚合物，其印迹系数为17，而仅以MAA为功能单体制备的基准聚合物的印迹系数为2.4。与先前报道的印迹聚合物相比，这种聚合物的印迹位置的饱和容量高出四到五倍。核磁共振滴定和分子动力学模拟证实了这些结果，表明这两个功能单体相对于E2 3-OH和17-OH基团具有正交性。优化后的聚合物表现出对EACS的保留率，这与它们对天然受体的抑制作用有关。通过在模型净水系统中使用优化的分子印迹聚合物(MIP)，它们能够完全去除水中一小群EAC的ppb水平。这与用于净水的非印迹聚合物和公认的吸附剂(例如，活性碳)的性能形成对比，后者在处理后仍含有可检测到的化合物数量。
Polymeric sorbents targeting endocrine-disrupting estrogen active compounds (EAC) were prepared by terpolymer imprinting using 17 beta-estradiol (E2) as template. From a group of eight functional monomers representing Bronsted acids, bases, hydrogen-bond donors and acceptors, as well as pi-interacting monomers, a terpolymer library that comprises all possible binary combinations of the functional monomers was prepared. Binding tests revealed that imprinted polymers exhibit a markedly higher affinity for E2 compared to nonimprinted polymers (NIPs) or polymers prepared by using single functional monomers. A combination of methacrylic acid (MAA) and p-vinylbenzoic acid offered a particularly promising lead polymer, displaying an imprinting factor of 17 versus 2.4 for a benchmark polymer prepared by using only MAA as functional monomer. The saturation capacities ascribed to imprinted sites were four to five times higher for this polymer compared to previously reported imprinted polymers. NMR titrations and molecular dynamics simulations corroborated these results, indicating an orthogonal preference of the two functional monomers with respect to the E2 3-OH and 17-OH groups. The optimized polymer exhibited a retentivity for EACs that correlates with their inhibitory effect on the natural receptor. By using the optimized molecularly imprinted polymers (MIPs) in a model water-purification system, they were capable of completely removing ppb levels of a small group of EACs from water. This is in contrast to the performance of nonimprinted polymers and well-established sorbents for water purification (e.g., active carbon), which still contained detectable amounts of the compounds after treatment.