Sun Hongmei, Hunter Christopher A, Llamas Eva Marina
Department of Chemistry , University of Sheffield , Sheffield S3 7HF , UK . Email:
Department of Chemistry , University of Cambridge , Lensfield Road , Cambridge CB2 1EW , UK.
Chem Sci. 2015 Feb 1;6(2):1444-1453. doi: 10.1039/c4sc03398a. Epub 2014 Dec 15.
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.
合成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契机。使用一系列紧密相关的锌卟啉 - 吡啶复合物来研究构象灵活性和几何互补性在决定分子识别事件选择性方面的相互作用。在两种不同溶剂甲苯和1,1,2,2 - 四氯乙烷（TCE）中测量了48种锌卟啉 - 吡啶复合物的缔合常数。这些缔合常数用于构建32个化学双突变循环，以剖析卟啉酚侧链与吡啶配体酯或酰胺侧链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比较来确定分子内相互作用的有效摩尔浓度（EM）。EM值不依赖于溶剂，并且对于位于配体框架同一位点的酰胺和酯氢键受体实际上是相同的。然而，根据用于将氢键受体连接到吡啶配体的连接子的灵活性，EM值存在一个数量级的变化。刚性芳族连接子给出的EM值比相应酯连接子的EM值高一个数量级，酯连接子具有一个额外的扭转自由度。然而，最灵活的醚连接子给出的EM值也高于相应酯连接子的EM值，酯连接子的扭转自由度少一个。尽管对于更灵活的醚连接子，结合时构象限制的代价更高，但这种灵活性允许配体与受体的几何互补性得到优化，因此在预组织和契合之间存在权衡。
