Solvent descriptors

How well can continuum solvation models distinguish changes in one or another of these solvent properties This is illustrated in Table 2, which compares solvation energies for three representative solutes in eight test solvents. Three of the test solvents are those shown in Table 1, one is water, and the other four were selected to provide useful comparisons on the basis of their solvent descriptors, which are shown in Table 3. Notice that all four solvents in Table 3 have no acidity, which makes them more suitable, in this respect, than 1-octanol or chloroform for modeling biomembranes. Table 2 shows that the SM5.2R model, with gas-phase geometries and semiempirical molecular orbital theory for the wave function, does very well indeed in reproducing all the trends in the data. 

Since there are so many solvents to choose from, it is natural that the search for guidelines for solvent selection has been intense. Researchers have tried to correlate enzyme activity, stability, and selectivity with different solvent descriptors, such as logP, dielectric constant, dipole moment, Hildebrand solubility parameters, and many others. When this approach is successful, the search for the optimal solvent can be limited to those having suitable values of the selected solvent descriptor(s). A list of solvent descriptors of a range of commonly used solvents is given in Table 1.4. 

Table 1.4 Solvent descriptors of organic solvents commonly used for biocatalysis. Sw/o (solubility of water in solvent, wt%) So/w (solubility of solvent in water, wt%) and e (dielectric constant) values from [78], log P (P = partition coefficient between octanol and water), ET (empirical polarity parameter by Reichardt-Dimroth) and HS (Hildebrand solubility parameter, )l, cm J, ) from [79].

Solvent effects on enzymatic reactions have been most thoroughly studied for esterification reactions. It has been observed that those reactions are favorably carried out in relatively hydrophobic solvents, while the equilibrium position is less favorable for esterification in more hydrophilic solvents. Correlations between equilibrium constants and solvent parameters have been evaluated. It was shown that the solubility of water in the solvent (Sw/0) gave better correlation with esterification equilibrium constants than log P and other simple solvent descriptors [61]. 

The situation is summarized from a slightly different perspective in Figure 2.2. Here, data obtained using the same set of organic solvents have been plotted. The porcine pancreatic lipase-catalyzed transesterification of sulcatol (6-methyl-5-hepten-2-ol) with butyric acid trifluoroethyl ester [81] has been chosen (arbitrarily) to calibrate the solvents. It is clear that, irrespective of the solvent descriptors that one may aim to investigate, different systems are seen to respond differently to the same (change of) medium. 

Despite the fact that solvent effects on enzyme enantioselectivity appear to resist our efforts to rationalize their outcome using commonly accepted solvent descriptors, the effects are certainly there. An impressive example is provided in a report on the successful resolution of ds/trans-( 1 R,5 R)-bicyclo[3.2.0]hept-6-ylidene-acetate ethyl esters, intermediates in the synthesis of GABA (y-aminobutyric acid) analogs, by the Pfizer Bio transformations and Global R D groups (Scheme 2.2) [136]. From a screening protocol, CaLB was identified as a reactive catalyst for the hydrolysis of the racemic mixture of / //-os lor enantiomers with approximately equal activity for the ds- and tmns-isomers and a rather modest (E = 2.7) preference for the /Z-(lR,5R)-enantiomers. Application of medium engineering resulted in a phenomenal increase in the enantioselectivity (addition of 40% acetone, E > 200), while the ds- and trans-isomers were still converted at an almost equal rate. 

Fig. 3-5. Geometrical representation of FA. The three-dimensional property space is defined by three solvent descriptors [e.g. tbp, fJ-, and r) and filled with 30 solvent points, some of them already lying in the plane defined by the two factors F and Fi (according to [139] and [142]).

Finally, a multiparameter correlation equation based solely on theoretically determined solvent descriptors, introduced by Famini and Wilson, deserves attention [350], Linear solvation energy relationships (LSERs), such as the KAT equation (7-54) and its successors, can be summarized by the general form shown in Eq. (7-66) ... 

Crowhurst L, Falcone R, Lancaster NL et al. (2006) Using Kamlet-Taft solvent descriptors to explain the reactivity of anionic nucleophiles in ionic liquids. J Org Chem 71 8847-8853... 

In view of these many roles, it is evident that all attempts at deriving single and unique scales of solvent descriptors accounting for all solvent "effects" should be regarded with scepticism. 

Descriptor 6, is the Reichardt-Dimroth (30) parameter[24] expressed in SI units. (30) defined as the transition energy (kcal) at 25 C of the long wave absorption band of standard betain dyes when dissolved in the solvent. Descriptor 8, log P is the logarithm of the equihbrium constant of the distribution of the solvent between 1-octanol and water at 25 °C. 

Ionic liquids with highly fluorinated anions can give rise to repulsions for this kind of interaction. The authors used the solvent descriptors to interpret previous chemical and chromatographic observations [12],... 

Among the approaches proposed so far, we recall here single-parameter models [102-111, 115, 118-120, 122, 123, 125, 126, 129], and multi-parametric correlation equations (either based on the combination of two or more existing scales or on the use of specific parameters to account for distinct types of effects) [112, 113, 116, 117, 121, 124]. Additional popular models are the Abraham s scales of solute hydrogen-bond acidity and solute hydrogen-bond basicity [127, 128], and the Catalan et al. solvatochromic scales [130,132, 133]. Methods based on quantitative stmcture-property relationships (QSPR) with solvent descriptors derived from the molecular structure [131, 134], and on principal component analysis (PCA) [135, 136] have been also proposed. An exhaustive review concerning the quantification of the solvent polarity has been recently published [138-140], including a detailed list of solvent scales, interrelations between parameters and statistical approaches. 

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