Krebs Institute, Department of Chemistry, University of Sheffield, Sheffield S3 7HF, United Kingdom.
J Am Chem Soc. 2009 Dec 30;131(51):18518-24. doi: 10.1021/ja9083495.
Chemical double mutant cycles have been used in conjunction with new H-bonding motifs for the quantification of chelate cooperativity in multiply H-bonded complexes. The double mutant cycle approach specifically deals with the effects of substituents, secondary interactions, and allosteric cooperativity on the free energy contributions from individual H-bond sites and allows dissection of the free energy contribution due to chelate cooperativity associated with the formation of intramolecular noncovalent interactions. Two different doubly H-bonded motifs were investigated in carbon tetrachloride, chloroform, 1,1,2,2-tetrachloroethane, and cyclohexane, and the results were similar in all cases, with effective molarities of 3-33 M for formation of intramolecular H-bonds. This corresponds to a free energy penalty of 3-9 kJ mol(-1) for formation of a bimolecular complex in solution, which is consistent with previous estimates of 6 kJ mol(-1). This result can be used in conjunction with the H-bond parameters, alpha and beta, to make a reasonable estimate of the stability constant for formation of a multiply H-bonded complex between two perfectly complementary partners, or to place an upper limit on the stability constant expected for a less complementary system.
化学双突变体循环已与新的氢键结合基序结合使用，用于定量多氢键复合物中的螯合协同作用。双突变体循环方法特别处理取代基、次级相互作用和变构协同作用对单个氢键位点的自由能贡献的影响，并允许由于与分子内非共价相互作用形成相关的螯合协同作用而导致的自由能贡献的剖析。在四氯化碳、氯仿、1,1,2,2-四氯乙烷和环己烷中研究了两种不同的双氢键基序，在所有情况下结果都相似，形成分子内氢键的有效摩尔浓度为 3-33 M。这对应于在溶液中形成双分子配合物的自由能罚分 3-9 kJ mol(-1)，与之前估计的 6 kJ mol(-1)一致。该结果可与氢键参数α和β结合使用，合理估计两个完全互补配体之间形成多氢键配合物的稳定常数，或对不太互补系统的稳定常数施加上限。
