Hunter Christopher A, Jones Philip S, Tiger Pascale, Tomas Salvador
Centre for Chemical Biology, Krebs Institute for Biomolecular Science, Department of Chemistry, University of Sheffield, Sheffield, S3 7HF, UK.
Chemistry. 2002 Dec 2;8(23):5435-46. doi: 10.1002/1521-3765(20021202)8:23<5435::AID-CHEM5435>3.0.CO;2-V.
Chemical double-mutant cycles have been used to quantify intermolecular functional-group interactions in H-bonded zipper complexes in chloroform. If the same interaction is measured in zippers of different overall stability, the double-mutant cycles can be combined to produce a triple-mutant box. This construct quantifies cooperativity between the functional group interaction of interest and the other interactions that are used to change the overall stability of the complexes. The sum of two edge-to-face aromatic interactions (-2.9 +/- 0.5 kJ mol-1) is shown to be insensitive to changes of up to 13.7 +/- 0.2 kJ mol-1 in the overall stability of the complex. In principle, enthalpic cooperative effects caused by entropy-enthalpy compensation could perturb the measurement of intermolecular interactions when using the double-mutant cycle approach, but these experiments show that, for this system, the magnitude of the effect lies within the error of the measurements.
化学双突变循环已被用于量化氯仿中氢键拉链复合物分子间官能团相互作用。如果在不同整体稳定性的拉链中测量相同的相互作用，双突变循环可以组合产生一个三突变盒。这种结构量化了感兴趣的官能团相互作用与用于改变复合物整体稳定性的其他相互作用之间的协同性。两个边对面芳香相互作用的总和（-2.9±0.5 kJ mol-1）显示对复合物整体稳定性高达13.7±0.2 kJ mol-1的变化不敏感。原则上，当使用双突变循环方法时，由熵焓补偿引起的焓协同效应可能会干扰分子间相互作用的测量，但这些实验表明，对于该系统，效应的大小在测量误差范围内。
