A new strategy for the design of water-soluble synthetic receptors: specific recognition of DNA intercalators and diamines.
A new strategy for the design of water-soluble synthetic receptors: specific recognition of DNA intercalators and diamines.
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水溶性合成受体设计的新策略：DNA嵌入剂和二胺的特异性识别。
DOI：
10.1002/chem.200204481
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
S. Kitagawa
中科院分区：
文献类型：
--
作者：
K. Wada;T. Mizutani;H. Matsuoka;S. Kitagawa
制备了在疏水环境中具有两个刘易斯酸性位点（锌）的水溶性锌双卟啉受体1和2，所述疏水环境由烷基链和双卟啉骨架组成，并被亲水外部（12或18个羧基）覆盖。该受体在水中对二胺和DNA嵌入剂显示出高亲和力，其中结合常数K（a）分别为10（7）和10（8）M（-1）的数量级。二胺和DNA嵌入剂通过不同的机制与受体结合。二胺通过疏水相互作用和锌-氮相互作用结合，而DNA嵌入剂通过疏水相互作用和电荷转移相互作用结合。柔性烷基链可以使货车与客体分子发生范德华接触，并通过诱导配合型机制在结合客体分子周围形成疏水环境。对于DNA嵌入剂的结合，以下特征是值得注意的：1）。锌卟啉和无锌卟啉的结合常数相似; 2）.具有较低LUMO的客体的结合常数较大;这表明电荷转移相互作用对结合的重要贡献; 3）. DNA嵌入剂的疏水性和阳离子性实质上是重要的，和4）。更高的离子强度降低了结合亲和力;这表明静电相互作用的中等贡献。受体的构象不稳定性也有助于紧密结合：在无客体受体中，疏水和静电相互作用不能同时有利。二胺和DNA嵌入剂结合时所观察到的焓-熵补偿的特征在于Δ H度与TDeltaS度图中相对较小的斜率（α =0.74）和较大的截距（β =7.75 kcal mol（-1））;这表明结合时发生受体的构象变化和显著的去溶剂化。该受体可以竞争性地结合碘化丙啶以剥夺DNA的插入碘化丙啶。这些功能的水溶性受体组成的刚性框架和灵活的侧链与一个大的溶剂可及的区域是在高度预组织的刚性受体相反，他们可以提供有用的指导，合理设计的诱导适合人工受体在水中。
Water-soluble zinc bisporphyrin receptors 1 and 2 having two Lewis acidic sites (zinc) in the hydrophobic environment consisting of alkyl chains and a bisporphyrin framework, and covered with hydrophilic exterior (twelve or eighteen carboxyl groups) were prepared. The receptors show high affinity for diamines and DNA intercalators in water where the binding constants K(a) are of the order of 10(7) and 10(8) M(-1), respectively. Diamines and DNA intercalators are bound to the receptor through different mechanisms. Diamines are bound through hydrophobic interactions and zinc-nitrogen interactions, while DNA intercalators are bound through hydrophobic interactions and charge-transfer interactions. Flexible alkyl chains can make van der Waals contact with guests and create a hydrophobic environment around the bound guest by an induced-fit-type mechanism. For the binding of DNA intercalators, the following features are noteworthy: 1). Binding constants are similar between the zinc porphyrins and zinc-free porphyrins; 2). the binding constant is larger for the guest having the lower LUMO; this indicates the important contribution of charge-transfer interactions to binding; 3). the hydrophobic and cationic nature of DNA intercalators is substantially important, and 4). higher ionic strength reduced the binding affinities; this shows a moderate contribution of electrostatic interactions. The conformational instability of the receptors also contributes to the tight binding: hydrophobic and electrostatic interactions cannot both be favorable at the same time in the guest-free receptor. Enthalpy-entropy compensation observed for the binding of diamines and DNA intercalators is characterized by a relatively small slope (alpha=0.74) and a large intercept (beta=7.75 kcal mol(-1)) in the DeltaH degrees versus TDeltaS degrees plot; this shows that a conformational change of receptors and a significant desolvation occur upon binding. The receptor can competitively bind to propidium iodide to deprive DNA of the intercalated propidium iodide. These features of water-soluble receptors consisting of a rigid framework and flexible side chains with a large solvent-accessible area are in contrast to highly preorganized rigid receptors, and they can provide useful guidelines for rational design of induced-fit artificial receptors in water.