pH-dependent binding of guests in the cavity of a polyhedral coordination cage: reversible uptake and release of drug molecules.
pH-dependent binding of guests in the cavity of a polyhedral coordination cage: reversible uptake and release of drug molecules.
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DOI：
10.1039/c4sc02090a
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发表时间：
2015-01-01
期刊：
影响因子：
8.4
通讯作者：
Ward MD
中科院分区：
文献类型：
--
作者：
Cullen W;Turega S;Hunter CA;Ward MD
含有酸性或碱性基团的有机客体在水溶性配位笼内的结合表现出很强的pH依赖性。一系列具有酸性或碱性基团的有机分子在多面体配位笼的腔内表现出强烈的ph依赖性结合。客体在水溶液中的结合主要是疏水作用，当客体变成阳离子（通过质子化）或阴离子（通过去质子化）时，这种作用被更强的溶剂化所补偿。帕金森氏症药物1-氨基金刚烷（“金刚烷胺”）以中性形式（pH大于11）结合，结合常数为104 M-1，但当客体在较低pH下质子化时，配合物的稳定性降低了三个数量级。由于宿主的顺磁性，结合客体的1H NMR信号的大前场偏移有助于监测客体进入笼腔的摄取。尽管结合常数通常较低，但具有生物学意义的客体，如阿司匹林和尼古丁，表现出类似的行为，无论带电物质的标志如何，中性（强结合）和带电（弱结合）形式之间存在实质性差异。我们观察到不同官能团（伯胺和叔胺、吡啶、咪唑和羧酸）的客体具有ph依赖性结合，因此ph的摆动可以在3.5-11的范围内任意调节。通过x射线晶体学测定了金刚烷-1-羧酸配合物的结构：客体的氧原子与宿主内表面两个等效口袋中的一个形成CH···O氢键。客体的可逆摄取和释放作为pH值的函数，在任何需要在外部刺激下控制分子释放的应用中提供了有趣的可能性。
Binding of organic guests containing acidic or basic groups inside a water-soluble coordination cage host shows strong pH dependence. A range of organic molecules with acidic or basic groups exhibit strong pH-dependent binding inside the cavity of a polyhedral coordination cage. Guest binding in aqueous solution is dominated by a hydrophobic contribution which is compensated by stronger solvation when the guests become cationic (by protonation) or anionic (by deprotonation). The Parkinson's drug 1-amino-adamantane (‘amantadine’) binds with an association constant of 104 M–1 in the neutral form (pH greater than 11), but the stability of the complex is reduced by three orders of magnitude when the guest is protonated at lower pH. Monitoring the uptake of the guests into the cage cavity was facilitated by the large upfield shift for the 1H NMR signals of bound guests due to the paramagnetism of the host. Although the association constants are generally lower, guests of biological significance such as aspirin and nicotine show similar behaviour, with a substantial difference between neutral (strongly binding) and charged (weakly binding) forms, irrespective of the sign of the charged species. pH-dependent binding was observed for a range of guests with different functional groups (primary and tertiary amines, pyridine, imidazole and carboxylic acids), so that the pH-swing can be tuned anywhere in the range of 3.5–11. The structure of the adamantane-1-carboxylic acid complex was determined by X-ray crystallography: the oxygen atoms of the guest form CH···O hydrogen bonds with one of two equivalent pockets on the internal surface of the host. Reversible uptake and release of guests as a function of pH offers interesting possibilities in any application where controlled release of a molecule following an external stimulus is required.
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