Force entropy effects

The equations we have written until now in this section impose no restrictions on the species they describe or on the origin of the interaction energy. Volume and entropy effects associated with reaction (8.A) will be less if x is not too large. Aside from this consideration, any of the intermolecular forces listed above could be responsible for the specific value of x- The relationships for ASj in the last section are based on a specific model and are subject to whatever limitations that imposes. There is nothing in the formalism for AH that we have developed until now that is obviously inapplicable to certain specific systems. In the next section we shall introduce another approximation... 

The solvophobic model of Hquid-phase nonideaHty takes into account solute—solvent interactions on the molecular level. In this view, all dissolved molecules expose microsurface area to the surrounding solvent and are acted on by the so-called solvophobic forces (41). These forces, which involve both enthalpy and entropy effects, are described generally by a branch of solution thermodynamics known as solvophobic theory. This general solution interaction approach takes into account the effect of the solvent on partitioning by considering two hypothetical steps. Eirst, cavities in the solvent must be created to contain the partitioned species. Second, the partitioned species is placed in the cavities, where interactions can occur with the surrounding solvent. The idea of solvophobic forces has been used to estimate such diverse physical properties as absorbabiHty, Henry s constant, and aqueous solubiHty (41—44). A principal drawback is calculational complexity and difficulty of finding values for the model input parameters. 

Figure 5.5 Comparing liposome-water to octanol-water partition coefficients of a series of uncharged substituted benzylalkylamines [387]. The membrane partitioning of the smaller members of the series (n — 0 3) is thought to be dominated by electrostatic and H-bonding effects (enthalpy-driven), whereas the partitioning of the larger members is thought to be directed by hydrophobic forces (entropy-driven) [387]. [Avdeef, A., Curr. Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

DiMarzio s subsequent calculation of the packing entropy-effect then yields rather small negative corrections to the Gaussian force, which are insufficient to explain the observed behaviour (see Fig. 27). 

An additional advantage of the force field method 32) is its power to predict the energy levels of conformations which are not populated and even complete rotational potentials of bonds. Again, statisfying agreement with results from dynamic nmr-measurements for a series of crowed hydrocarbons was found 36). Knowledge of the shape of rotational potentials proved to be helpful for the interpretation of entropy effects in these series of compounds and in their thermolysis reactions. 

This conformational situation is also responsible for entropy effects. It has been shown 161 that the entropy differences between two diastereomers in this series is mainly dependent on the shapes of the rotational profiles about the central bonds. The observed differences in AS (D,L-meso) for the thermolyses can be reproduced semiquantitatively by differences in ground state entropy (see Table 2) which were calculated by the force field method 53). 

Marked differences between observed and predicted results occur, however, when the entropy effects are too great to be ignored. In the derivation of Eqs. 4 and 5, only dispersion forces between molecular components were taken into... 

A theoretical treatment of complex coacervation was worked out by Voorn (4,5) and Overbeek and Voorn (6). They explained the process as a competition between the electrical attractive forces tending to accumulate the charged pxxLyions and entropy effects... 

Aped et al. (214) used the MM3 force field to calculate the minimum energy conformations of propellane 120 and the corresponding transition states on the inversion path (Scheme 36). A comparison of the inversion barriers calculated for the overall process (86 kj/mol) and found experimentally by NMR measurements (49 kJ/mol) led the authors to the conclusion that it is difficult to obtain accurate results, since MM3 is currently not well parametrized for the gauche effect also the solvent and entropy effects could not be properly assessed (214). 

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