Desolvation contribution

Constanciel R and R Contreras 1984. Self-Consistent Field Theory of Solvent Effects Representation by Continuum Models - Introduction of Desolvation Contribution. Theoretica Chimica Acta 65 1-11. 

R. Constanciel and R. Contreras, Self-consistent field theory of solvent effects representation by continuum models-introduction of desolvation contribution, Theor. Chim. Acta 65 1 (1984). 

We now review the weak points in each of the probes that we have considered. The Marcus analysis may be wrong because, as discussed above, the barrier is M-shaped, or because there are very large desolvation contributions to w, or because the whole theory is inapplicable. We believe that the evidence we have presented shows that the basic Marcus pattern of reactivity is found and that the theory can be used. Secondly, the effect of desolvation... 

Theory of Solvent Effects. Representation by Continuum Models—Introduction of Desolvation Contribution. 

If considerable endothermic effect of the ionic association for acid can be explained by desolvation contribution of ionic pair formation (i.e., solvated moleeule of acid), the endothermic effect of ionic pair formation by such voluminous cations contradicts the physical model of the process. Estimation of desolvation energy of ionic pair formation of salt ions according to the equation shows that this energy is two orders of magnitude lower than the energy of heat movement of solvent molecules. For this reason, the process of ionic association of salt ions is exothermal, as seen from AH-p values. The exothermal character increases with permittivity decreasing, i.e., with increase of ion-ion interaction energy. 

Putting aside issues of the molecular origin of hydrophobic effect , the more significant issue is the extent to which desolvation contributes to overall binding thermodynamics. A variety of experimental methodologies to evaluate the magnitude of this effect exist. The most commonly used tools are Hansch transfer parameters [30, 31]. Briefly, a series of eompounds are partitioned between water and water-saturated octanol. The value n is then derived for a substitutent according to the expression ... 

The direct ligand-protein interactions and the net solvation-desolvation term together should give an energy contribution that strongly favors formation of the complex (large and negative), since the other two components favor its dissociation. 

A qualitative difference in the type of solvation (not simply in the strength of solvation) in a series of nucleophiles may contribute to curvature. Jencks has examined this possibility. " " An example is the reaction of phenoxide, alkoxide, and hydroxide ions with p-nitrophenyl thiolacetate, the Br insted-type plot showing Pnuc = 0.68 for phenoxide ions (the weaker nucleophiles) and Pnu = 0.17 for alkoxide ions. It is suggested that the need for desolvation of the alkoxide ions prior to nucleophilic attack results in their decreased nucleophilicity relative to the phenoxide ions, which do not require this desolvation step. 

The possibility of an entropy-enthalpy relationship for the reaction was examined and found to give a correlation coefficient of only 0.727 which was however improved to 0.971 if only the external contributions to these parameters were used, i.e. these contributions arising from solvent interactions only. If compounds with substituents ortho to the amino group were excluded, this further improved to 0.996 and is likely therefore to be real [cf. the comments on p. 9). It was argued that the different amounts of desolvation of the aromatic on going to the transition state would depend upon the substituent, and that the resultant greater freedom for solvent molecules would mean decreased interaction energy or increased enthalpy so that the linear relationship follows. 

The DS increase as a function of increasing the chain-length of the acyl group may be also attributed to hydrophobic interactions between the cellu-losic surface, whose hydrophobic character increases as a function of increasing DS, and the acylating species. This cooperative interaction. Fig. 10, may contribute to the activation enthalpy, as a result of desolvation of the entering species. Since association between the chains attached to cellulose and those... 

There is also an entropy term associated with the desolvation of the ligands. This is much more difficult to assess, and may make for either favourable or unfavourable contributions to the overall entropy changes. 

The second group of studies tries to explain the solvent effects on enantioselectivity by means of the contribution of substrate solvation to the energetics of the reaction [38], For instance, a theoretical model based on the thermodynamics of substrate solvation was developed [39]. However, this model, based on the determination of the desolvated portion of the substrate transition state by molecular modeling and on the calculation of the activity coefficient by UNIFAC, gave contradictory results. In fact, it was successful in predicting solvent effects on the enantio- and prochiral selectivity of y-chymotrypsin with racemic 3-hydroxy-2-phenylpropionate and 2-substituted 1,3-propanediols [39], whereas it failed in the case of subtilisin and racemic sec-phenetyl alcohol and traws-sobrerol [40]. That substrate solvation by the solvent can contribute to enzyme enantioselectivity was also claimed in the case of subtilisin-catalyzed resolution of secondary alcohols [41]. 

Sims, P.A. Wong, C.R Vuga, D. McCammon, J.A. Sefton, B.R, Relative contributions of desolvation, inter- and intramolecular contributions to binding affinity in protein kinase systems, J. Comput. Chem. 2005, 26, 668-681... 

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