Thermodynamics of hydrogen bond and hydrophobic interactions in cyclodextrin complexes.
Values of K, delta G(o), delta H(o), delta S(o) and delta C(po) for the binding reaction of small organic ligands forming 1:1 complexes with either alpha- or beta-cyclodextrin were obtained by titration calorimetry from 15 degrees C to 45 degrees C. A hydrogen bond or hydrophobic interaction was introduced by adding a single functional group to the ligand. The thermodynamics of binding with and without the added group are compared to estimate the contribution of the hydrogen bond or hydrophobic interaction. A change in the environment of a functional group is required to influence the binding thermodynamics, but molecular size-dependent solute-solvent interactions have no effect. For phenolic O-H-O hydrogen bond formation, delta H(o) varies from -2 to -1.4 kcal mol(-1) from 15 degrees C to 45 degrees C, and delta C(p) is increased by 18 cal K(-1) mol(-1). The hydrophobic interaction has an opposite effect: in alpha-cyclodextrin, delta C(po) = -13.3 cal K(-1) mol(-1) per ligand -CH(2)-, identical to values found for the transfer of a -CH(2)-group from water to a nonpolar environment. At room temperature, the hydrogen bond and the -CH(2)-interaction each contribute about -600 cal mol(-1) to the stability (delta G(o)) of the complex. With increased temperature, the hydrogen bond stability decreases (i.e., hydrogen bonds "melt"), but the stability of the hydrophobic interaction remains essentially constant.
Ross
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PD
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0560 USA.
Rekharsky
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MV
D000588:Amines; D002151:Calorimetry; D002236:Carbohydrate Conformation; D018360:Crystallography, X-Ray; D003505:Cyclodextrins / Q000737:chemistry*; D003511:Cyclohexanols; D006860:Hydrogen Bonding; D008024:Ligands; D010627:Phenethylamines; D010654:Phenylbutyrates; D010666:Phenylpropionates; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014439:Tyramine
D000588:Amines; D003505:Cyclodextrins; D003511:Cyclohexanols; D008024:Ligands; D010627:Phenethylamines; D010654:Phenylbutyrates; D010666:Phenylpropionates; C029261:phenethylamine; C036032:3-phenylbutyric acid; C035253:3-phenylpropionic acid; D014439:Tyramine