Hydrogen bond formation, thermodynamics

The Hydrogen Bond Formation, Thermodynamic Properties, Classification... 

D. J. Tobias and C. L. Brooks, Thermodynamics of amide hydrogen bond formation in... 

Because intermolecular hydrogen bonds between small molecules are usually made and broken very rapidly relative to the chemical shift difference between bonded and nonbonded forms (expressed in hertz), separate lines are generally not observed for different species, and the frequency v of the single observed line is given by Eq. 2.58. In suitable systems the variation of v with concentration and temperature can be analyzed to give equilibrium constants and other thermodynamic properties for hydrogen bond formation. 

The experimental determination of Aff and AS sometimes yields surprising results, as, for example, in the thermodynamics of hydrogen-bond formation in the complex of FK506 or rapamycin with FK506-binding protein (FKBP). " Binding to the wild-type and to the mutant Tyr 82 Phe 82 was... 

In order to determine to what extent these speculations have validity, it is necessary to be able to evaluate more quantitatively the relative contributions of these interactions to the free energies of protein and nucleic acid molecules in water and nonaqueous solvents. For this purpose, a substantial body of quantitative data is required concerning the properties of suitable model compounds in a variety of solvents, including their solubilities, acid-base dissociation constants, and thermodynamics of hydrogen bond formation. The dearth of pertinent data on hydrogen bonds in solvents of interest is particularly frustrating to even a semiquantitative evaluation of the scheme presented in Fig. 7. 

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