Solvent Effects 1 Solvation

To account for indirect solvent effects, solvation models must allow for geometry optimizations and frequency calculations including the solute-solvent interactions. Indeed, many ab initio continuum solvation models and in particular those belonging to the family of the PCM [3] provide analytical first and second derivatives of the free energy with respect to the nuclear coordinates [4,5], In the following we shall present in detail the formalism for the derivatives in the PCM and Conductor-PCM (CPCM) [6] models. 

Reactions of this charge type appear to be rather insensitive to solvent polarity and to protic-dipolar aprotic solvent effects. Solvation of the trimethylsulphonium cation is expected to decrease quite strongly in... 

For analysing equilibrium solvent effects on reaction rates it is connnon to use the thennodynamic fomuilation of TST and to relate observed solvent-mduced changes in the rate coefficient to variations in Gibbs free-energy differences between solvated reactant and transition states with respect to some reference state. Starting from the simple one-dimensional expression for the TST rate coefficient of a unimolecular reaction a— r... 

Cramer C J and Truhlar D G 1996 Continuum solvation models Solvent Effects and Ohemical Reactivity ed O Tapia and J Bertran (Dordrecht Kluwer) pp 1-80... 

The GB equation is suitable for the description of solvent effects in molecular mechanics and dynamics [16], as well as in quantum mechanical calculations (17,18]. An excellent review of implicit solvation models, with more than 900 references, is given by Cramer and Truhlar [19]. 

Solvation can have a profound effect on the results of a chern ical calculation, Th is is especially true wh en tti e solute an d solven t are polar or when they can participate in hydrogen honding. The solvent effect is expressed in several ways, including these ... 

In a few cases, where solvent effects are primarily due to the coordination of solute molecules with the solute, the lowest-energy solvent configuration is sufficient to predict the solvation effects. In general, this is a poor way to model solvation effects. 

There is no one best method for describing solvent effects. The choice of method is dependent on the size of the molecule, type of solvent effects being examined, and required accuracy of results. Many of the continuum solvation methods predict solvation energy more accurately for neutral molecules than for ions. The following is a list of preferred methods, with those resulting in the highest accuracy and the least amount of computational effort appearing first ... 

The continuum model, in which solvent is regarded as a continuum dielectric, has been used to study solvent effects for a long time [2,3]. Because the electrostatic interaction in a polar system dominates over other forces such as van der Waals interactions, solvation energies can be approximated by a reaction field due to polarization of the dielectric continuum as solvent. Other contributions such as dispersion interactions, which must be explicitly considered for nonpolar solvent systems, have usually been treated with empirical quantity such as macroscopic surface tension of solvent. 

Solvent effects on chemical equilibria and reactions have been an important issue in physical organic chemistry. Several empirical relationships have been proposed to characterize systematically the various types of properties in protic and aprotic solvents. One of the simplest models is the continuum reaction field characterized by the dielectric constant, e, of the solvent, which is still widely used. Taft and coworkers [30] presented more sophisticated solvent parameters that can take solute-solvent hydrogen bonding and polarity into account. Although this parameter has been successfully applied to rationalize experimentally observed solvent effects, it seems still far from satisfactory to interpret solvent effects on the basis of microscopic infomation of the solute-solvent interaction and solvation free energy. 

It should always be home in mind that solvent effects can modify the energy of both tile reactants and the transition slate. It is the difference in the two solvation effects that is the basis for changes in activation energies and reaction rates. Ihus, although it is conimon to express solvent effects solely in terms of reactant solvation or transition-slate solvation,... 

Having considered how solvents can affect the reactivities of molecules in solution, let us consider some of the special features that arise in the gas phase, where solvation effects are totally eliminated. Although the majority of organic preparative reactions and mechanistic studies have been conducted in solution, some important reactions are carried out in the gas phase. Also, because most theoretical calculations do not treat solvent effects, experimental data from the gas phase are the most appropriate basis for comparison with theoretical results. Frequently, quite different trends in substituent effects are seen when systems in the gas phase are compared to similar systems in solution. 

In fee absence of fee solvation typical of protic solvents, fee relative nucleophilicity of anions changes. Hard nucleophiles increase in reactivity more than do soft nucleophiles. As a result, fee relative reactivity order changes. In methanol, for example, fee relative reactivity order is N3 > 1 > CN > Br > CP, whereas in DMSO fee order becomes CN > N3 > CP > Br > P. In mefeanol, fee reactivity order is dominated by solvent effects, and fee more weakly solvated N3 and P ions are fee most reactive nucleophiles. The iodide ion is large and very polarizable. The anionic charge on fee azide ion is dispersed by delocalization. When fee effect of solvation is diminished in DMSO, other factors become more important. These include fee strength of fee bond being formed, which would account for fee reversed order of fee halides in fee two series. There is also evidence fiiat S( 2 transition states are better solvated in protic dipolar solvents than in protic solvents. 

Other measures of nucleophilicity have been proposed. Brauman et al. studied Sn2 reactions in the gas phase and applied Marcus theory to obtain the intrinsic barriers of identity reactions. These quantities were interpreted as intrinsic nucleo-philicities. Streitwieser has shown that the reactivity of anionic nucleophiles toward methyl iodide in dimethylformamide (DMF) is correlated with the overall heat of reaction in the gas phase he concludes that bond strength and electron affinity are the important factors controlling nucleophilicity. The dominant role of the solvent in controlling nucleophilicity was shown by Parker, who found solvent effects on nucleophilic reactivity of many orders of magnitude. For example, most anions are more nucleophilic in DMF than in methanol by factors as large as 10, because they are less effectively shielded by solvation in the aprotic solvent. Liotta et al. have measured rates of substitution by anionic nucleophiles in acetonitrile solution containing a crown ether, which forms an inclusion complex with the cation (K ) of the nucleophile. These rates correlate with gas phase rates of the same nucleophiles, which, in this crown ether-acetonitrile system, are considered to be naked anions. The solvation of anionic nucleophiles is treated in Section 8.3. 

Because the key operation in studying solvent effects on rates is to vary the solvent, evidently the nature of the solvation shell will vary as the solvent is changed. A distinction is often made between general and specific solvent effects, general effects being associated (by hypothesis) with some appropriate physical property such as dielectric constant, and specific effects with particular solute-solvent interactions in the solvation shell. In this context the idea of preferential solvation (or selective solvation) is often invoked. If a reaction is studied in a mixed solvent. 

Because the positive pole is relatively sheltered from close approach, these solvents cannot effectively solvate anions, which, therefore, display an enhanced nucleophilicity... 

As the plot of AE indicates, the energy difference between the two forms decreases in more polar solvents, and becomes nearly zero in acetonitrile. The left plot illustrates the fact that the IPCM model (at the B3LYP/6-31+G(d) level of theory) does a much better job of reproducing the observed solvent effect than the two Onsager SCRF models. In contrast, the Onsager model at the MP2 level treats the solvated systems more accurately than it does the gas phase system, leading to a poorer value for the solvent effect. ... 

The substituent effects on the H-bonding in an adenine-uracil (A-U) base pair were studied for a series of common functional groups [99JPC(A)8516]. Substitutions in the 5 position of uracil are of particular importance because they are located toward the major groove and can easily be introduced by several chemical methods. Based on DFT calculation with a basis set including diffuse functions, variations of about 1 kcal/mol were found for the two H-bonds. The solvent effects on three different Watson-Crick A-U base pairs (Scheme 100) have been modeled by seven water molecules creating the first solvation shell [98JPC(A)6167]. 

It should be emphasized again that both the SN1 and the 5 2 reaction show solvent effects but that they do so for different reasons. SN2 reactions are disfavored in protic solvents because the ground-state energy oi the nucleophile is lowered by solvation. S l reactions are favored in protic solvents because the transition-state energy leading to carbocation intermediate is lowered by solvation. 

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