Solvation/desolvation effects

Extensive structural characterization of many different -ring heterocycles has not yet been done. Difficulties predicting relative potency of these compounds a priori stem from the lack of understanding of solvation/desolvation effects as well as difficulties in characterizing the low-intensity hydrophobic interactions. Consequently, it seems likely that new structure—activity relationships about the A-ring heterocycle will continue to be determined based on empirical findings. 

Solvation/desolvation effects in the cryptand also complicate the expected simple dependence of stability constant on host basicity. For example the aliphatic cryptand O-bistren shows lower formation constants than the less basic aromatic analogues such as R3F, which we attribute to the greater desolvation cost of complexation with the former, more hydrophilic host. 

There exists substantial evidence that in reactions that involve oxyanions or amines as bases or as nucleophiles, their partial desolvation, as they enter the transition state, typically has made greater progress than bond formation. In the context of the PNS, this partial loss of solvation represents the early loss of a reactant stabilizing factor and hence reduces the intrinsic rate constant. As discussed at some length in our 1992 chapter,4 for strongly basic oxyanions this desolvation effect often manifests itself in terms of negative deviations from Br Ansted plots and/or in abnormally low p or pnuc values.58,188 In fact, a number of cases have been reported where the pnuc value was close to zero or... 

Solvation and desolvation effects are of tremendous importance in assessing binding equilibria. 

The lack of correlation with enthalpic (i.e. bond length-related) data highlights the complexity of the system, and the need to consider solvation/desolvation-related effects as contributing significantly to the free energies of complexation. 

The effects of solvation/desolvation equilibria on the thermodynamics of complexation can be discerned in the pattern of formation constant values across a series of azaciyptand hosts or anionic guests. In the dianionic series thiosulfate, selenate, sulfate, formation constants, to a first approximation, decrease as the hydration energy of the anion increases, reflecting the enthalpic cost of desolvation. 

The contribution of hydrogen bonds to the binding affinity strongly depends on solvation and desolvation effects. Here lies the biggest challenge... 

The solubility of various liquids in water, and vice versa, is of much interest in different industrial and biological phenomena of everyday importance (Table 3.13). ° In any of these applications, we would encounter instances where a prediction of solubility would be of interest the following such applications are mentioned for general interest. Furthermore, solubilities of molecules in a fluid are determined by the free energy of solvation. In more complicated processes such as catalysis, the reaction rate is related to the desolvation effects. 

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