Substrate solvation

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]. 

When substrate activities are used instead of substrate concentrations in studies of enzyme kinetics in organic media, solvent effects due to substrate solvation disappear. Remaining solvent effects should be due to direct interactions between the enzyme and the solvent. In a study of lipase-catalyzed esterification reactions, it was found that Km values based on activities were indeed more similar tban those based on concentrations in different solvents, but still some differences remained [49]. 

As discussed in Section 1.2.3, it is crucial tbat the effects of solvents are studied at fixed water activity, or else indirect effects due to competition for water between enzyme and solvent will cause strong effects and mask the true solvent effects. In general, when correcting for substrate solvation, hydrophobic solvents seem to give higher rates than other solvents [5]. 

Jonsson, A. A., Wehtje, E., and Adlercreutz, P, Low reaction temperature increases the selectivity in an enzymatic reaction owing to substrate solvation effects, Biotechnol. Lett., 19, 85-88 1997. 

Figure 8-6. Kinetic parameters for subtilisin-catalyzed transesterification of Z-Ala-ONp in different solvents. Experimental Km (O) and Vm/Km ( ) values are shown as a function of substrate solubility. The filled symbols show the corresponding "corrected values, after allowing for substrate solvation. The variation in Vm/Km is largely explained by solvation, while the real variation in Km is opposite to the apparent trend. Reimann et al.1261.

Many apparent solvent effects reported in the literature are actually due to changes in the availability of water or substrate to the enzyme. It is commonly observed that activity appears to be highest in the least polar solvents. Sometimes the explanation will be added that these have the least tendency to strip water from the enzyme . This undoubtedly indicates a common mechanism, but in such cases the solvent effect will disappear completely if experiments are run at equal water activity, as recommended in the discussion above (Sect. 8.3.1 and Fig. 8-2). Many other observed solvent effects operate via changes in substrate solvation, as explained in Sect. 8.5. Hence, they are really effects of changing substrate availability when different solvents are compared with equal substrate concentrations. 

As water can act as a competitive nucleophile in transesterification reactions, these reactions should be performed under anhydrous conditions. Acylation reactions in pure organic media have been shown to give reduced yields and rates of reaction because the lid is thought to remain predominantly closed. The reduction in activity could also be due to changes in the pH of un-buffered organic solutions and changes to the substrate solvation. 

C.K. Savile, R.. Kazlauskas, How substrate solvation contributes to the enantioselectivity of subtilisin toward secondary alcohols, 1. Am. Chem. Soc. 127 (2005) 12228-12229. 

Phase transfer catalysis succeeds for two reasons First it provides a mechanism for introducing an anion into the medium that contains the reactive substrate More important the anion is introduced m a weakly solvated highly reactive state You ve already seen phase transfer catalysis m another form m Section 16 4 where the metal complexmg properties of crown ethers were described Crown ethers permit metal salts to dissolve m nonpolar solvents by surrounding the cation with a lipophilic cloak leav mg the anion free to react without the encumbrance of strong solvation forces... 

Adsorption of bath components is a necessary and possibly the most important and fundamental detergency effect. Adsorption (qv) is the mechanism whereby the interfacial free energy values between the bath and the soHd components (sofld soil and substrate) of the system are lowered, thereby increasing the tendency of the bath to separate the soHd components from one another. Furthermore, the soHd components acquire electrical charges that tend to keep them separated, or acquire a layer of strongly solvated radicals that have the same effect. If it were possible to foUow the adsorption effects in a detersive system, in all their complex ramifications and interactions, the molecular picture of soil removal would be greatly clarified. 

Based on the calculation of the solvatation free energy of methylene fragment with carboxyl at the aliphatic carboxylic acids extraction, the uniqueness of cloud-point phases was demonstrated, manifested in their ability to energetically profitably extract both hydrophilic and hydrophobic molecules of substrates. The conclusion is made about the universality of this phenomenon and its applicability to other kinds of organized media on the surfactant base. 

Entry 4 shows that reaction of a secondary 2-octyl system with the moderately good nucleophile acetate ion occurs wifii complete inversion. The results cited in entry 5 serve to illustrate the importance of solvation of ion-pair intermediates in reactions of secondary substrates. The data show fiiat partial racemization occurs in aqueous dioxane but that an added nucleophile (azide ion) results in complete inversion, both in the product resulting from reaction with azide ion and in the alcohol resulting from reaction with water. The alcohol of retained configuration is attributed to an intermediate oxonium ion resulting from reaction of the ion pair with the dioxane solvent. This would react until water to give product of retained configuratioiL When azide ion is present, dioxane does not efiTectively conqiete for tiie ion-p intermediate, and all of the alcohol arises from tiie inversion mechanism. ... 

Within the framework of Monte Carlo simulations, the relation between measurable quantities and the microscopic structure of confined phases can now be examined. An example of such a measurable quantity is the solvation force F h)/2 KR (see Sec. IIA 1). From a theoretical perspective and according to the discussion in Sec. IIA 3 its investigation requires the stress T zisz) exerted normally by a confined fluid on planar substrates [see Eqs. (19) and (22)]. Using Eqs. (11) and (53) one can derive a molecular expression for Tzz from... 

To illustrate the relationship between the microscopic structure and experimentally accessible information, we compute pseudo-experimental solvation-force curves F h)/R [see Eq. (22)] as they would be determined in SEA experiments from computer-simulation data for T z [see Eqs. (93), (94), (97)]. Numerical values indicated by an asterisk are given in the customary dimensionless (i.e., reduced) units (see [33,75,78] for definitions in various model systems). Results are correlated with the microscopic structure of a thin film confined between plane parallel substrates separated by a distance = h. Here the focus is specifically on a simple fluid in which the interaction between a pair of film molecules is governed by the Lennard-Jones (12,6) potential [33,58,59,77,79-84]. A confined simple fluid serves as a suitable model for approximately spherical OMCTS molecules confined... 

M. Schoen, T. Gnihn, D. J. Diestler. Solvation forces in thin films between macroscopically curved substrates. J Chem Phys 709 301-311, 1998. 

As pointed out by Chapman et the steric requirements of the reagents and the degree of solvation of the substrate at the reacting center should also be considered when comparing the nucleophilicities of different amines toward different substrates. The large number of factors which may be involved clearly call for much more work in this area. 

The effects of the nucleophile on aromatic substitution which are pertinent to our main theme of relative reactivity of azine rings and of ring-positions are brought together here. The influence of a nucleophile on relative positional reactivity can arise from its characteristics alone or from its interaction with the ring or with ring-substituents. The effect of different nucleophiles on the rates of reaction of a single substrate has been discussed in terms of polarizability, basicity, alpha effect (lone-pair on the atom adjacent to the nucleophilic atom), and solvation in several reviews and papers. ... 

Alkali metals in liquid ammonia can transfer an electron to the solvent, leading to so-called solvated electrons. These can add to the aromatic substrate 1 to give a reduced species, the radical anion 3 ... 

The rate acceleration imposed by 0-cyclodextrin was explained in terms of a microsolvent effect 6> The inclusion of the substrate within the hydrophobic cavity of cyclodextrin simulates the changes in solvation which accompany the transfer of the substrate from water to an organic solvent. Uekama et al.109) have analyzed the substituent effect on the alkaline hydrolysis of 7-substituted coumarins (4) in the... 

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