Solvation of Transition States

Fig. 4.12. Potential energy liagrams showing effect of preferential solvation of transition state (a) and ground state (b) on the activation energy.

The effect of solvation of transition states has been discussed in relation to aromatic nucleophilic substitution. 

Application, through equation (9), of the solvent activity coefficient concept to the rate data in Table 17 for 8 2 reactions of Nj and SCN in methanol and in DMF, illustrates some interesting features of solvation of transition states (Coniglio et al., 1966). In equations (37) and (38) fc(Cl) and A (I) are rate constants and (Cl) and (I) are transition statesfor... 

Solvation of Transition States for Isomerisation and Solvolysis in the cis and ti-ans-[CoCl2(en)2] System at 25°C... 

As pointed out by Taft and co-workers (27) on the basis of linear free energy relationships, highly polar transition states are prime candidates to undergo specific solvation by polar or polarizable species. This concept was already set forth in 1935 by Wynne-Jones and Eyring (35) on an entirely different basis, namely, the interpretation of kinetic results in mixed solvents (36). The study of reaction rates in mixed solvents is an almost untapped source of information on the solvation of transition states, Recently, Drougard and Decroocq (37) have studied the kinetics of the Menschutkin reaction between EtsN and Mel in binary and ternary solvent systems. From their experimental data it appears that... 

Increase in activation energy (26.3 kcal/mol) owing to weaker solvation of transition state... 

Since ditriptoyl peroxide is electrically symmetrical, and since benzene is not outstanding in its ability to solvate polar transition states, it seems probable that the inversion reaction in this case is due to the rearrangement of an acyloxy radical rather than cation. It may be that failure to isolate comparable products from other peroxides under free radical conditions is due to competition from very fast substitution... 

The negative AS was explained in terms of the solvation of the transition state by the reaction medium. Dimerisation reduces the polar nature of acetic acid. Hence, in 1% acetic acid the polar transition state is thought to freeze the benzene molecules, thus producing a negative AS (—5.8 e.u./mol). When the acetic acid concentration is increased, the monomers of acetic acid solvate the transition state preferentially and the... 

One of the major objectives of physical organic chemistry is the detailed description of transition states in terms of nuclear positions, charge distributions, and solvation requirements. A considerable aid to this task is provided for many reaction series by the existence of extrathermodynamic relationships, whose mathematical simplicity largely arises from extensive cancellation of the contribution to the free-energy change from the part of the molecule outside the reaction zone. 

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. ... 

Nevertheless, important features of real solvent reactions were reproduced by microsolvation. The role of ion-molecule complexes, important in the gas phase, decreased rapidly with introduction of solvent molecules, the reaction profile becoming nearly unimodal (see Continuum solvation, below). Activation energies for both E2 and SN2 processes increased due to stronger solvation of reactants than of transition states (although in this work, because of imposed geometric... 

Figure 9. Schematic representation of upper portion of potential eneigy surface for merging of substitution mechanisms. A Sjsj 1 mechanism. No nucleophilic solvation in transition state ion pair intermediate (possibly nudeophilically solvated) B Sn2 (intermediate). Transition state is nudeophilically solvated by solvent (SOH) intermediate is a nudeophilically solvated ion pair (see Fig. 8) C Classical Sn2. No energy minimum. In curves A and B, the second transition state may be of higher energy than the first in cases where internal return is important.

Perhaps the most spectacular success of explanations based on solvation of ground states, published to date, is the dissection of activation parameters for solvolysis of t-butyl chloride in mixtures of ethanol and water, first discussed by Winstein and Fainberg (1957). The complex variation of AH and AS (Fig. 21) has been shown to be due almost entirely to ground state solvation effects, at least for the solvents ethanol—40% ethanol/water studied by Arnett et al. (1965). For 90%, 80%, 70%, 60%, 50% and 40% ethanol/water the parameter AH1 for solvation of the transition state (by transfer from the gas phase) was calculated to be linearly proportional to the corresponding value of AS, as expected from the behaviour of simple salts. The point for pure ethanol did not fall on the calculated line, and this was attributed to nucleophilic solvent assistance. The variation in AG, AH and AS (Fig. 21) can be reproduced remarkably well using ethane and the zwitterionic a-amino acid, glycine, as model compounds (Abraham et al., 1975 see also Abraham, 1974 Abraham and Abraham, 1974). 

A process following the rate law shown in Eq. (20.65) is said to be an SN1 (substitution, nucleophilic, unimolecular) process. The term unimolecular refers to the fact that a single species is required to form the transition state. Because the rate of such a reaction depends on the rate of dissociation of the M-X bond, the mechanism is also known as a dissociative pathway. In aqueous solutions, the solvent is also a potential nucleophile, and it solvates the transition state. In fact, the activated complex in such cases would be indistinguishable from the aqua complex [ML H20] in which a molecule of H20 actually completes the coordination sphere of the metal ion after X leaves. This situation is represented by the dotted curve in Figure 20.1 where the aqua complex is an intermediate that has lower energy than [ML,]. The species [ML H20] is called an intermediate because it has a lower energy than that of the activated complex, [MLJ. 

The observed decreases in catalysis of the substituted enzymes may be a consequence of increased energy barriers due to the losses of transition state solvation. The effect seems to be mainly on "galactosylation" (k2). This is supported by the results of the nucleophilic competition studies which showed that the addition of methanol to the assay did not result in an increase in the kcat-Furthermore, the kcat values for each enzyme were quite different depending upon which substrate was used. This indicates that "galactosylation" (ka) was rate determining, and shows that this step was affected much more than "degalactosylation" (ks) by the changes in solvation of the planar transition state. 

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