Release of High-Energy Water as an Essential Driving Force for the High-Affinity Binding of Cucurbit[n]urils
Release of High-Energy Water as an Essential Driving Force for the High-Affinity Binding of Cucurbit[n]urils
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DOI：
10.1021/ja303309e
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发表时间：
2012-09-19
影响因子：
15
通讯作者：
De Simone, Alfonso
中科院分区：
文献类型：
--
作者：
Biedermann, Frank;Uzunova, Vanya D.;De Simone, Alfonso
分子动力学模拟和等温滴定量热（ITC）实验表明，在水溶液中，高能量水从葫芦[n]脲（CBN）大环空腔中的释放是客体结合的主要决定因素.单个包封水分子的能量随着空腔尺寸的增加而降低，因为更大的空腔允许形成更稳定的氢键网络。相反，内部水的总能量随着空腔尺寸的增加而增加，因为水分子的绝对数量增加。对于CB7，它已经成为一种亲油性结合剂，这些抵消作用导致通过从空腔中完全去除水分子获得最大的能量。因此，出现了一种新的水性合成受体的设计标准，其是相对于驻留水分子的能量和数量优化空腔和结合口袋的尺寸。
Molecular dynamics simulations and isothermal titration calorimetry (ITC) experiments with neutral guests illustrate that the release of high-energy water from the cavity of cucurbit[n]uril (CBn) macrocycles is a major determinant for guest binding in aqueous solutions. The energy of the individual encapsulated water molecules decreases with increasing cavity size, because larger cavities allow for the formation of more stable H-bonded networks. Conversely, the total energy of internal water increases with the cavity size because the absolute number of water molecules increases. For CB7, which has emerged as an ultrahigh affinity binder, these counteracting effects result in a maximum energy gain through a complete removal of water molecules from the cavity. A new design criterion for aqueous synthetic receptors has therefore emerged, which is the optimization of the size of cavities and binding pockets with respect to the energy and number of residing water molecules.