Differential solvation

However, the Baker-Nathan effect has now been shown not to be caused by hyperconjugation, but by differential solvation. This was demonstrated by the finding that in certain instances where the Baker-Nathan effect was found to apply in solution, the order was completely reversed in the gas phase. ° Since the molecular structures are unchanged in going from the gas phase into solution, it is evident that the Baker-Nathan order in these cases is not caused by a structural feature (hyperconjugation) but by the solvent. That is, each alkyl group is solvated to a different extent. 

Considering that, roughly speaking, the electrostatic component of the solvation free energy varies as the cube of the molecular dipole moment, it becomes obvious that the corrective term (13.1) should be taken into account in the determination of differential solvation properties of very polar solutes. In the computation of transfer free energies across an interface, it has been suggested that equation (13.1) be expressed as a function of the number density of one of the two media, so that the correction is zero in solvent 1 and zl,l lsl lll in solvent 2 [115]. 

In conjunction with the present review we have carried out AM1-SM4 calculations in solvent -hexadecane (e = 2.06) for the benzotriazole equilibrium. We find that 35 is better solvated than 34 by 0.9 kcal/mol, with all of the differential solvation being found in the AG pterm. Not surprisingly, PM3-SM4 results are very similar. This seems to be out of step with the data from CDCb, the most nonpolar solvent for which experimental results are available. It is not clear, however, whether this difference is attributable to (i) the smaller dielectric constant of -hexadecane compared to CDCb (for CHCb e = 4.8 at 293 K [240]), (ii) specific interactions between weakly acidic chloroform and the basic benzotriazole tautomers, (iii) inadequacies in the semiempirical electronic structure, (iv) inadequacies in the SM4 model, or (v) some combination of any or all of the above. When SM5 models are available for CHCI3 and DMSO, it will be interesting to revisit this system. 

The 2-substituted system has proven especially attractive to modelers because the experimental equilibrium constants are known both in the gas phase and in many different solutions. As a result, the focus of the modeling study can be on the straightforward calculation of the differential solvation free energy of the two tautomers, without any requirement to first accurately calculate the relative tautomeric free energies in the gas phase. However, in 1992 Les et al. [290] suggested that prior experimental data [240,266,288], primarily in the form of ultraviolet spectra in the gas phase and in low-temperature matrices, had been misinterpreted and that the reported equilibrium constants referred to homomeric dimers of tautomers (i.e., (42)2 (43)2). Parchment et al. [291] contested this... 

Calculations on the differential solvation free energies of the two relevant tautomers are presented in the following table for several different models implemented at a number of levels of theory. The following discussion will focus on comparing specific calculations in the table. 

Young et al. [195] have provided a calculation in which they compared expanding the multipole series up to /= 6 in a spherical cavity of 3.8 A. These results may be compared directly to those of Wong et al. [297] at the identical level of theon asis set in order to assess the effect of including higher moments. In each case, the differential solvation free energy increases by about 40%. This illustrates nicely the relationship between cavity radius and model... 

In this form of catalysis, inclusion of the substrate in the CD cavity provides an environment for the reaction that is different from that of the bulk, normally aqueous, medium. In the traditional view, the catalytic effect arises from the less polar nature of the cavity (a microdielectric effect) and/or from the conformational restraints imposed on the substrate by the geometry of inclusion (Bender and Komiyama, 1978). However, catalysis may also arise as a result of differential solvation effects at the interface of the CD cavity with the exterior aqueous environment (Tee and Bennett, 1988a,b Tee, 1989). 

The different solvation energetics of R and R- will also lead to errors in the bond dissociation enthalpies calculated with equation 16.33. For instance, in the case of phenol, whose interactions with proton-acceptor solvents (like DMSO) are obviously stronger than those for the phenoxy radical, a negative correction should be applied to the value of Z)//°(PhO-H) calculated from equation 16.33 (see also equation 16.32). It is probably unwise to ascribe the 7 kJ mol-1 difference between the electrochemical and the recommended DH° (PhO—R) value to the differential solvation effects. Although this discrepancy is in the correct direction, it lies within the suggested uncertainty of the method. 

Cl, the differential solvation effect is more pronounced for these cases and, hence, the barrier to exchange is large. However, our work predicts and demonstrates qualitatively identical behavior in the gas phase as well, and thus provides the first evidence that the low reactivity of alkoxides toward others is at least, in part, an intrinsic property of the reaction system and not due exclusively to differential solvation. 

In all of these compounds solvolysis will lead to a tertiary ion. The series [10], [13], [11] clearly indicates the strain argument, and one may note that the difference in rates between [1] and [11] corresponds to an energy difference of only 1 1 kcal mole . The data do not prove that non-classical stabilization of the transition state in [1] and [12] is not partly responsible for the rate differences but rather suggests that relief of striiin could account for the results. Other factors, particularly differential solvation of the ground state and transition state and the possibility that solvolysis may not be of a limiting type but involve reaction with solvent, may also play a role but are difficult to evaluate. In any case the rate of solvolysis of exo-compounds does not appear to be unusually rapid when viewed in this light. 

Due to the popularity of THF as an eluent for GPC, this sort of "differential solvation" must be kept in mind, particularly when polar solutes are analyzed. This effect can also work against resolution in SMGPC, as demonstrated in Figure 1. Here BHA and BHT are fully resolved in CHCI3 but coelute in THF. Both BHA and BHT have phenolic sites, but the site on BHT is sterically hindered and apparently does not form a hydrogen bond with THF. The hydrogen bonded BHA/THF complex which does form... 

Procedures " for distinguishing between the two means of facilitation include (1) Use of a reagent that does not bind as an affinity label. If facilitation is due to hyperreactivity, this reagent should also be more reactive. (2) Use of transition-state analysis. A favorable change in the entropy of activation (A ) would imply facilitation via affinity labeling whereas a more favorable change in the enthalpy of activation (AH ) implies hyperreactivity. However, a certain caution should always be exercised since other factors, e.g. differential solvation effects, can result in a certain degree of compensation between AH and AS. ... 

Besides affecting equilibria and kinetics on single energy surfaces, differential solvation effects on distinct electronic states can cause significant changes in UV-Vis absorption spectra. Such so-called solvatochromic effects are discussed in more detail in Chapter 14. 

Only the force-field energy term associated with interactions between the biotin and avidin fragments remains. This is added to the differential solvation free energies and differential thermal terms to determine the full binding free energy. 

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