Dissection of Complex Molecular Recognition Interfaces
Dissection of Complex Molecular Recognition Interfaces
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DOI：
10.1021/ja1084783
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发表时间：
2011-01-26
影响因子：
15
通讯作者：
Turega, Simon M.
中科院分区：
文献类型：
--
作者：
Hunter, Christopher A.;Misuraca, Maria Cristina;Turega, Simon M.
具有外围氢键功能的锌卟啉和吡啶配体家族的合成提供了获得各种密切相关的具有零到四个分子内氢键的超分子配合物的途径。自动紫外/可见滴定系统用于表征 120 种不同的复合物，这些数据用于构建大量不同的化学双突变体循环，以量化分子内氢键相互作用。结果探讨了控制复杂分子识别界面组装中协同性的定量结构活性关系。具体来说，配合物化学结构的变化使我们能够改变超分子结构、构象灵活性、几何互补性、氢键相互作用的数量和性质以及配合物的整体稳定性。各个氢键的自由能贡献是相加的，并且形成分子内相互作用的有效摩尔浓度随结构的变化非常小。在几何上不可能存在的复合物中，没有观察到分子内氢键，但也不存在出色的几何互补性导致非常高的亲和力的情况。同样，构象灵活性的变化似乎对有效摩尔浓度（EM）值的影响有限。使用双突变体循环检查的所有 48 种分子内相互作用发现的主要变化是，分子内羧酸酯-苯酚氢键 (200 mM) 的 EM 值比磷酸二酯-苯酚氢键 (30 mM) 的 EM 值大一个数量级。相应的分子间膦酸二酯-苯酚氢键比羧酸酯苯酚氢键稳定2个数量级，并且EM的巨大差异可能是由于某种补偿效应，其中更强的氢键更难形成，因为它对配合物的几何形状施加了更严格的限制。
The synthesis of a family of zinc porphyrins and pyridine ligands equipped with peripheral H-bonding functionality has provided access to a wide range of closely related supramolecular complexes featuring between zero and four intramolecular H-bonds. An automated UV/vis titration system was used to characterize 120 different complexes, and these data were used to construct a large of number of different chemical double mutant cycles to quantify the intramolecular H-bonding interactions. The results probe the quantitative structure activity relationship that governs cooperativity in the assembly of complex molecular recognition interfaces. Specifically, variations in the chemical structures of the complexes have allowed us to change the supramolecular architecture, conformational flexibility, geometric complementarity, the number and nature of the H-bond interactions, and the overall stability of the complex. The free energy contributions from individual H-bonds are additive, and there is remarkably little variation with architecture in the effective molarity for the formation of intramolecular interactions. Intramolecular H-bonds are not observed in complexes where they are geometrically impossible, but there are no cases where excellent geometric complementarity leads to very high affinities. Similarly, changes in conformational flexibility seem to have limited impact on the values of effective molarity (EM). The major variation that was found for all of the 48 intramolecular interactions that were examined using double mutant cycles is that the values of EM for intramolecular carboxylate ester-phenol H-bonds (200 mM) are an order of magnitude larger than those found for phosphonate diester-phenol H-bonds (30 mM). The corresponding intermolecular phosphonate diester-phenol H-bonds are 2 orders of magnitude more stable than carboxylate ester phenol H-bonds, and the large differences in EM may be due to some kind of compensation effect, where the stronger H-bond is harder to make, because it imposes tighter constraints on the geometry of the complex.