title: Chemical triple-mutant boxes for quantifying cooperativity in intermolecular interactions.
abstract: 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.
authors.affiliation: Centre for Chemical Biology, Krebs Institute for Biomolecular Science, Department of Chemistry, University of Sheffield, Sheffield, S3 7HF, UK. c.hunter@sheffield.ac.uk
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hunter
authors.forename: Philip S
authors.initials: PS
authors.lastname: Jones
authors.forename: Pascale
authors.initials: P
authors.lastname: Tiger
authors.forename: Salvador
authors.initials: S
authors.lastname: Tomas
mesh_terms: D006860:Hydrogen Bonding; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008968:Molecular Conformation; D013816:Thermodynamics