Nanomolar Binding of Steroids to Cucurbit[n]urils: Selectivity and Applications
Nanomolar Binding of Steroids to Cucurbit[n]urils: Selectivity and Applications
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DOI：
10.1021/jacs.6b07655
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发表时间：
2016-10-05
影响因子：
15
通讯作者：
Nau, Werner M.
中科院分区：
文献类型：
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作者：
Lazar, Alexandra I.;Biedermann, Frank;Nau, Werner M.
葫芦[n]urils （CBn, n = 7,8）作为类固醇（21个测试）的人工受体，包括激素睾酮和雌二醇以及类固醇药物。荧光位移滴定和等温滴定量热法（ITC）在水溶液中为这些疏水靶分子提供了高达纳摩尔的结合亲和力，超过了已知的合成受体的值。通过核磁共振、x射线晶体衍射、ITC和量子化学计算，详细研究了其显著的结合选择性，甚至对同源类固醇对也是如此。值得注意的是，CBn中心点类固醇复合物在水和缓冲液、人工胃酸甚至血清中都是稳定的。已经证明了许多应用，其范围从类固醇在大环存在下的溶解度增强（高达100倍，用于药物递送）和不同CBn中心点报告染料组合的荧光响应的主成分分析（用于类固醇的差异传感）到类固醇作为底物的化学转化的实时监测（用于酶测定）。
Cucurbit[n]urils (CBn, n = 7, 8) serve as artificial receptors for steroids (21 tested), including the hormones testosterone and estradiol as well as steroidal drugs. Fluorescence displacement titrations and isothermal titration calorimetry (ITC) provided up to nanomolar binding affinities in aqueous solution for these hydrophobic target molecules, exceeding the values of known synthetic receptors. Remarkable binding selectivities, even for homologous steroid pairs, were investigated in detail by NMR, X-ray crystal diffraction, ITC, and quantum chemical calculations. Notably, the CBn center dot steroid complexes are stable in water and buffers, in artificial gastric acid, and even in blood serum. Numerous applications have been demonstrated, which range from the solubility enhancement of the steroids in the presence of the macrocycles (up to 100 times, for drug delivery) and the principal component analysis of the fluorescence responses of different CBn center dot reporter dye combinations (for differential sensing of steroids) to the real-time monitoring of chemical conversions of steroids as substrates (for enzyme assays).