The flexibility-complementarity dichotomy in receptor-ligand interactions.
The flexibility-complementarity dichotomy in receptor-ligand interactions.
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DOI：
10.1039/c4sc03398a
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发表时间：
2015-02-01
期刊：
影响因子：
8.4
通讯作者：
Llamas EM
中科院分区：
文献类型：
--
作者：
Sun H;Hunter CA;Llamas EM
合成的超分子复合物为定量系统地探索化学结构与分子识别现象之间的关系提供了机会。使用一系列密切相关的锌卟啉-吡啶复合物来检查构象灵活性和几何互补性在确定分子识别事件的选择性方面的相互作用。在甲苯和 1,1,2,2-四氯乙烷 (TCE) 两种不同溶剂中测量了 48 种锌卟啉-吡啶配合物的缔合常数。这些缔合常数用于构建 32 个化学双突变体循环，以剖析卟啉苯酚侧臂与吡啶配体的酯或酰胺侧臂之间分子内氢键的自由能贡献。通过与相应的分子间氢键相互作用进行比较，确定分子内相互作用的有效摩尔浓度 (EM)。 EM 的值不取决于溶剂，并且对于位于配体框架上相同位点的酰胺和酯氢键受体来说实际上是相同的。然而，EM 存在一个数量级的变化，具体取决于用于连接氢键受体与吡啶配体的连接体的灵活性。刚性芳族连接体的 EM 值比相应酯连接体的 EM 值高一个数量级，酯连接体具有一个额外的扭转自由度。然而，最灵活的醚连接体给出的 EM 值也高于相应酯连接体的 EM 值，而相应的酯连接体的扭转自由度要少一个。尽管对于更灵活的醚连接体来说，结合构象限制的惩罚更高，但这种灵活性允许优化受体配体的几何互补性，因此在预组织和拟合之间存在权衡。结合亲和力不会随着预组织而均匀增加，因为灵活性和适合性之间存在权衡。
Synthetic supramolecular complexes provide an opportunity for quantitative systematic exploration of the relationship between chemical structure and molecular recognition phenomena. A family of closely related zinc porphyrin–pyridine complexes was used to examine the interplay of conformational flexibility and geometric complementarity in determining the selectivity of molecular recognition events. The association constants of 48 zinc porphyrin–pyridine complexes were measured in two different solvents, toluene and 1,1,2,2-tetrachloroethane (TCE). These association constants were used to construct 32 chemical double mutant cycles to dissect the free energy contributions of intramolecular H-bonds between the phenol side arms of the porphyrins and the ester or amide side arms of the pyridine ligands. Effective molarities (EM) for the intramolecular interactions were determined by comparison with the corresponding intermolecular H-bonding interactions. The values of EM do not depend on the solvent and are practically identical for amide and ester H-bond acceptors located at the same site on the ligand framework. However, there are variations of an order of magnitude in EM depending on the flexibility of the linker used to connect the H-bond acceptors to the pyridine ligands. Rigid aromatic linkers give values of EM that are an order of magnitude higher than the values of EM for the corresponding ester linkers, which have one additional torsional degree of freedom. However, the most flexible ether linkers give values of EM that are also higher than the values of EM for the corresponding ester linkers, which have one less torsional degree of freedom. Although the penalty for conformational restriction on binding is higher for the more flexible ether linkers, this flexibility allows optimization of the geometric complementarity of the ligand for the receptor, so there is a trade off between preorganization and fit. Binding affinity does not increase uniformly with preorganization, because there is a trade off between flexibility and fit.
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影响因子：
15
作者：
Hogben, Hannah J.;Sprafke, Johannes K.;Anderson, Harry L.
通讯作者：
Anderson, Harry L.
影响因子：
8.4
作者：
Hunter, Christopher A.;Misuraca, Maria Cristina;Turega, Simon M.
通讯作者：
Turega, Simon M.
影响因子：
15
作者：
Hunter, Christopher A.;Misuraca, Maria Cristina;Turega, Simon M.
通讯作者：
Turega, Simon M.
影响因子：
8.4
作者：
Hunter, Christopher A.;Misuraca, Maria Cristina;Turega, Simon M.
通讯作者：
Turega, Simon M.
影响因子：
15
作者：
Hunter, Christopher A.;Misuraca, Maria Cristina;Turega, Simon M.
通讯作者：
Turega, Simon M.