New ultrahigh affinity host-guest complexes of cucurbit[7]uril with bicyclo[2.2.2]octane and adamantane guests: thermodynamic analysis and evaluation of M2 affinity calculations.
New ultrahigh affinity host-guest complexes of cucurbit[7]uril with bicyclo[2.2.2]octane and adamantane guests: thermodynamic analysis and evaluation of M2 affinity calculations.
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DOI：
10.1021/ja109904u
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发表时间：
2011-03-16
影响因子：
15
通讯作者：
Gilson MK
中科院分区：
文献类型：
--
作者：
Moghaddam S;Yang C;Rekharsky M;Ko YH;Kim K;Inoue Y;Gilson MK
先前已证明二茂铁衍生物能够在水中以超高亲和力 (ΔGo= -21 kcal/mol) 结合葫芦[7]脲 (CB[7])。在这里，我们描述了同样能很好地结合水性 CB[7] 的新化合物，验证了我们之前的建议，即它们也将是超高亲和力的 CB[7] 客体。目前的客体基于双环[2.2.2]辛烷或金刚烷核心，没有金属原子，因此这些结果也证实基于二茂铁的客体的显着高亲和力不必归因于金属特异性相互作用。因为我们在合成几个新的主客体系统之前使用 M2 方法来计算它们的亲和力，所以目前的结果也为这种计算方法的首次盲评估提供了依据。盲法计算与实验相当吻合，并成功地重现了新的基于金刚烷的客体实现极高亲和力的观察结果，尽管事实上它们仅将阳离子取代基定位在 CB[7] 宿主的一个电负性门户上。然而，也存在与实验的显着偏差，这导致了程序错误的校正以及计算对分子能量参数的物理合理变化的敏感性的指导性评估。这里提出的新实验和计算结果涉及分子识别的物理机制、M2方法的准确性以及主客体系统作为计算方法测试台的有用性。
A dicationic ferrocene derivative has previously been shown to bind cucurbit[7]uril (CB[7]) in water with ultra-high affinity (ΔGo= −21 kcal/mol). Here, we describe new compounds that bind aqueous CB[7] equally well, validating our prior suggestion that they, too, would be ultra-high affinity CB[7] guests. The present guests, which are based upon either a bicyclo[2.2.2]octane or adamantane core, have no metal atoms, so these results also confirm that the remarkably high affinities of the ferrocene-based guest need not be attributed to metal-specific interactions. Because we used the M2 method to compute the affinities of several of the new host-guest systems prior to synthesizing them, the present results also provide for the first blinded evaluation of this computational method. The blinded calculations agree reasonably well with experiment and successfully reproduce the observation that the new adamantane-based guests achieve extremely high affinities, despite the fact that they position a cationic substituent at only one electronegative portal of the CB[7] host. However, there are also significant deviations from experiment, and these lead to the correction of a procedural error and an instructive evaluation of the sensitivity of the calculations to physically reasonable variations in molecular energy parameters. The new experimental and computational results presented here bear on the physical mechanisms of molecular recognition, the accuracy of the M2 method, and the usefulness of host-guest systems as test-beds for computational methods.
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影响因子：
5.5
作者：
Chen, Wei;Gilson, Michael K.;Potter, Michael J.
通讯作者：
Potter, Michael J.
影响因子：
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