Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, U.K.
J Am Chem Soc. 2017 May 17;139(19):6675-6681. doi: 10.1021/jacs.7b01765. Epub 2017 May 3.
High-throughput UV-vis titrations in combination with chemical double-mutant cycles (DMCs) have been used to study the competition of a polar solvent for formation of intramolecular H-bonds. Twenty-four different zinc porphyrin-pyridine complexes were investigated in mixtures of toluene and phenol. DMCs were used to determine effective molarities (EM) for the formation of intramolecular phenol-amide H-bonds as a function of solvent composition. The values of EM increase by an order of magnitude with increasing concentrations of the more polar solvent, phenol. Phenol solvates the amide groups on the ligands strongly, increasing the steric bulk and destabilizing the complexes. These adverse steric interactions are removed when intramolecular H-bonds are formed and therefore provide an increased driving force for formation of cooperative interactions. The result is that the effects of competitive interactions with polar solvents that reduce binding affinity are attenuated to a significant extent by a corresponding increase in EM in multivalent complexes.
高通量紫外-可见滴定法与化学双突变体循环（DMC）结合使用，研究了极性溶剂对形成分子内氢键的竞争。在甲苯和苯酚的混合物中研究了 24 种不同的锌卟啉-吡啶配合物。DMC 用于确定形成分子内苯酚酰胺氢键的有效摩尔浓度（EM），作为溶剂组成的函数。随着更极性溶剂苯酚浓度的增加，EM 值增加了一个数量级。苯酚强烈地溶剂化配体上的酰胺基团，增加了空间位阻并使配合物不稳定。当形成分子内氢键时，这些不利的空间相互作用被消除，因此为形成协同相互作用提供了更大的驱动力。结果是，与降低结合亲和力的极性溶剂的竞争相互作用的影响在多价配合物中通过 EM 的相应增加在很大程度上被减弱。
