Acidity solvation effects

An understanding of a wide variety of phenomena concerning conformational stabilities and molecule-molecule association (protein-protein, protein-ligand, and protein-nucleic acid) requires consideration of solvation effects. In particular, a quantitative assessment of the relative contribution of hydrophobic and electrostatic interactions in macromolecular recognition is a problem of central importance in biology. 

This is opposite from the order in solution as revealed by the pK data in water and DMSO shown in Table 4.14. These changes in relative acidity can again be traced to solvation effects. In the gas phase, any substituent effect can be analyzed directly in terms of its stabilizing or destabilizing effect on the anion. Replacement of hydrogen by alkyl substituents normally increases electron density at the site of substitution, but this effect cannot be the dominant one, because it would lead to an ordering of gas-phase acidity opposite to that observed. The dominant effect is believed to be polarizability. The methyl... 

Shifts in the SEC fractionation range are not new. It has been known for decades that adding chaotropes to mobile phases causes proteins to elute as if they were much larger molecules. Sodium dodecyl sulfate (SDS) (9) and guanidinium hydrochloride (Gd.HCl) (9-12) have been used for this purpose. It has not been clearly determined in every case if these shifts reflect effects of the chaotropes on the solutes or on the stationary phase. Proteins are denatured by chaotropes the loss of tertiary structure increases their hydrodynamic radius. However, a similar shift in elution times has been observed with SEC of peptides in 0.1% trifluoroacetic acid (TEA) (13-15) or 0.1 M formic acid (16), even if they were too small to have significant tertiary structure. Speculation as to the cause involved solvation effects that decreased the effective pore size of the... 

Richardson WEI, Peng C, Bashford D, Noodleman L, Case DA (1997) Incorporating Solvation Effects into Density Functional Theory Calculation of Absolute Acidities. Int J Quantum Chem 61 207-217. 

When the gas-phase reactions, such as the relative acidities or basicities were compared with their counterparts in solution (in a solvent such as water) it was generally found16,17 that the energetics in the solvent were strongly affected by solvation effects and particularly the solvation of the ionic reactants. Relationships between the gas-phase and solution-phase reactions and the solvation energies of the reactants are generally obtained through thermodynamic cycles. From the cycle,... 

The lesser acidity of sterically hindered alcohols such as tert-butyl alcohol arises from solvation effects. 

In addition to heterocycles, other molecular systems have attracted theoretical attention with respect to prediction of tautomeric equilibria and solvation effects thereon. The most commonly studied example in this class is the equilibrium between formamide and formamidic acid, discussed in the next section. In addition, some continuum modeling of solvation effects on keto/enol equilibria have appeared these are presented in section 4.2.2.2. We note that the equilibrium... 

In this contribution, we describe and illustrate the latest generalizations and developments[1]-[3] of a theory of recent formulation[4]-[6] for the study of chemical reactions in solution. This theory combines the powerful interpretive framework of Valence Bond (VB) theory [7] — so well known to chemists — with a dielectric continuum description of the solvent. The latter includes the quantization of the solvent electronic polarization[5, 6] and also accounts for nonequilibrium solvation effects. Compared to earlier, related efforts[4]-[6], [8]-[10], the theory [l]-[3] includes the boundary conditions on the solute cavity in a fashion related to that of Tomasi[ll] for equilibrium problems, and can be applied to reaction systems which require more than two VB states for their description, namely bimolecular Sjy2 reactions ],[8](b),[12],[13] X + RY XR + Y, acid ionizations[8](a),[14] HA +B —> A + HB+, and Menschutkin reactions[7](b), among other reactions. Compared to the various reaction field theories in use[ll],[15]-[21] (some of which are discussed in the present volume), the theory is distinguished by its quantization of the solvent electronic polarization (which in general leads to deviations from a Self-consistent limiting behavior), the inclusion of nonequilibrium solvation — so important for chemical reactions, and the VB perspective. Further historical perspective and discussion of connections to other work may be found in Ref.[l],... 

The Lewis acid-base reaction leading to complex formation910 has been recently11 considered in relation to the role of solvation effects. Many scales of thermodynamic parameters have been suggested. The concept of donor number (DN) was proposed by Gutmann12, and defined as the AH (kcalmol-1) for the interaction of a basic solvent with SbCL in 1,2-dichloromethane at room temperature ... 

Over the last decade, many approaches have been proposed for relating acidity-basicity dependent properties in gas phase and solution. To evaluate the solvation effect, the... 

The acidity dependence of the activation enthalpies and entropies, All and AS. of the hydration of 1,3-cyclohexa- and 1,3-cyclooctadienes was ascribed30 to a dielectric solvation effect in dilute acids, which is overcome by increasing solvent structure as the availability of water decreased in concentrated acids. This suggestion was one of the early premises of a more recent interpretation31 of acidity effects in terms of water activity and solvation of cationic species. 

Attempts to obtain alkylcarbonium complexes by dissolving alkyl chlorides (bromides) in liquid Lewis acid halides (stannic chloride, titanium (IV) chloride, antimony pentachloride, etc.) as solvent were unsuccessful. Although stable solutions could be obtained at low temperature with, for example, t-butyl chloride, the observed N.M.R. chemical shifts were generally not larger than 0 5 p.p.m. and thus could be attributed only to weak donor-acceptor complexes, but not to the carbonium ions. The negative result of these investigations seems to indicate that either the Lewis acids used were too weak to cause sufficient ionization of the C—Cl bond, or that the solvating effect of the halides... 

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