Department of Chemistry, University of Sheffield, Sheffield S3 7HF, United Kingdom.
J Am Chem Soc. 2011 Jan 26;133(3):582-94. doi: 10.1021/ja1084783. Epub 2010 Dec 21.
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.
合成了一系列带有外围氢键功能的锌卟啉和吡啶配体，这些配体可用于制备具有 0 到 4 个分子内氢键的多种紧密相关的超分子配合物。采用自动化 UV/vis 滴定系统对 120 种不同的配合物进行了表征，并利用这些数据构建了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协同性的定量结构-活性关系。具体而言，通过改变配合物的化学结构，我们可以改变超分子结构、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。单个氢键的自由能贡献是可加的，并且在形成分子内相互作用的有效摩尔浓度方面，其与架构的变化非常小。在几何上不可能存在分子内氢键的配合物中观察不到氢键，但在几何互补性非常好的情况下，并没有出现高亲和力的情况。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。在使用双突变体循环检查的 48 个分子内相互作用中，发现所有相互作用的主要变化是，分子内羧酸酯-苯酚氢键的 EM 值（200mM）比膦酸二酯-苯酚氢键的 EM 值（30mM）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，EM 值的巨大差异可能归因于某种补偿效应，即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。
