Zwitterion solvation effect

Fig. 2.6 Comparison of the calculated structures for glycine in the gas-phase and in water (COSMO solvation model). Note that the central bond angle in the zwitterionic form 1 is distorted by the hydrogen bond length of 1.96A computed for this structure in the gas phase. When solvation effects are included in the calculation using COSMO, the electrostatic interaction is reduced in magnitude due to charge screening by water, and the bond angle distortion is no longer present.

We can appreciate that ionization of the carboxylie acid is affected by the electron-withdrawing inductive effect of the ammonium residue hence the increased acidity when compared with an alkanoic acid. Similarly, loss of a proton from the ammonium cation of the zwitterion is influenced by the electron-donating inductive effect from the carboxylate anion, which should make the amino group more basic than a typical amine. That this is not the case is thought to be a solvation effect (compare simple amines). 

Bernhardsson and coworkers have recently used CASPT2 calculations (electron-correlation correction to the CAS wave function) to model carbonyl oxides in solution. Solvation effects in acetonitrile solvent also suggest that the zwitterionic form would be favored with an elongation of the 0—0 bond length and a decrease in the C—O bond. Ab initio calculations have been recently reported for monofluorocarbonyl oxide , diflu-orocarbonyl oxide , methylcarbonyl oxide and cyclopropenone carbonyl oxide. In the recent literature the idea that carbonyl oxide can be an important source of OH radicals has also been presented. ... 

Effects of solvation on zwitterion formation between methylamine and fom-aldehydewere studied by various solvation methods. The SM2/AM1 model predicted the expected zwitterionc minimum while SM3/PM3 failed to do so [127]. Calculations were performed with the use of AMSOL to account for solvation effects in the study of molecular properties and pharmacokinetic behavior of ce-tirizine, a zwitterionic third-generation antihistaminic. Results indicated that the folded conformation remains of low energy not only in vacuo but also in water solution [128]. 

It should be emphasized that solvation of excited electronic states is fundamentally different from the solvation of closed-shell solutes in the electronic ground state. In the latter case, the solute is nonreactive, and solvation does not significantly perturb the electronic structure of the solute. Even in the case of deprotonation of the solute or zwitterion formation, the electronic structure remains closed shell. Electronically excited solutes, on the other hand, are open-shell systems and therefore highly perceptible to perturbation by the solvent environment. Empirical force field models of solute-solvent interactions, which are successfully employed to describe ground-state solvation, cannot reliably account for the effect of solvation on excited states. In the past, the proven concepts of ground-state solvation often have been transferred too uncritically to the description of solvation effects in the excited state. In addition, the spectroscopically detectable excited states are not necessarily the photochemically reactive states, either in the isolated chromophore or in solution. Solvation may bring additional dark and photoreactive states into play. This possibility has hardly been considered hitherto in the interpretation of the experimental data. 

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). 

Applications of the Born—Kirkwood-Onsager model at the ab initio level include investigations of solvation effects on sulfamic acid and its zwitterion,23i an examination of the infrared spectra of formamide and formamidic acid,222 and a number of studies focusing on heterocyclic tautomeric equilibria.222,232,233 a more detailed comparison of some of the heterocyclic results is given later. The gas phase dipole moment depends on basis set, and systematic studies of this dependence are available. Furthermore, the effects of basis set choice and level of correlation analysis have been explored in solvation studies as well,222,233 but studies to permit identification of particular trends in their impact on the solvation portion of the calculation are as yet insufficient. 

The and ffp constants for the 2-pyridyl group found from the pK, of pyridyl-2-benzoic acids (series 10, X = 2-pyridyl) in 50% eq. ethanol (77JMC304) appear to be questionable due to the possible manifestation of strong solvation effects and formation of zwitterionic structures 11. Hence... 

Sukumar, N., and G. A. Segal. 1986. Effect of Aqueous Solvation upon the Electronic Excitation Spectrum of the Glycine Zwitterion A Theoretical Cl Study Using a Fractional Charge Model. J. Am. Chem. Soc. 108, 6880-6884. 

Interpretation of KIEs on enzymatic processes (see Chapter 11) has been frequently based on the assumption that the intrinsic value of the kinetic isotope effect is known. Chemical reactions have long been used as models for catalytic events occurring in enzyme active sites and in some cases this analogy has worked quite well. One example is the decarboxylation of 4-pyridylacetic acid presented in Fig. 10.9. Depending on the solvent, either the zwitterionic or the neutral form dominates in the solution. Since the reaction rates in D20/H20 solvent mixtures are the same (see Section 11.4 for a discussion of aqueous D/H solvent isotope effects), as are the carbon KIEs for the carboxylic carbon, it is safe to assume that this is a single step reaction. The isotope effects on pKa are expected to be close to the value of 1.0014 determined for benzoic acid. This in mind, changes in the isotope effects have been attributed to changes in solvation. 

DFT was employed to study the mechanism of ammonolysis of phenyl formate in the gas phase, and the effect of various solvents on the title reaction was assessed by the polarizable continuum model (PCM). The calculated results show that the neutral concerted pathway is the most favourable one in the gas phase and in solution.24 The structure and stability of putative zwitterionic complexes in the ammonolysis of phenyl acetate were examined using DFT and ab initio methods by applying the explicit, up to 7H20, and implicit PCM solvation models. The stability of the zwitterionic tetrahedral intermediate required an explicit solvation by at least five water molecules with stabilization energy of approximately 35 kcalmol-1 25... 

The mechanism of the addition of aldehydes and ketones to group 14 dimetallenes has been examined through a theoretical study. It was found that for reactions in which a Si-O bond is formed, both diradical and zwitterionic intermediates are possible. However, the presence of diradical intermediates was not found for Ge-O bond-forming reactions. Solvation simulations were performed to examine the effect of solvent polarity on the reaction energetics <2002JA13306>. 

In the isolation of water-soluble compounds, small amounts of water can dissolve significant amounts of material and have an adverse effect on processing. The pyridinyl carboxylic acid 7 was isolated after adjusting the pH to the isoelectric point, at which the zwitterion displayed minimal solubility (Figure 11.8) [25]. Water was removed by azeotropic distillation to facilitate the isolation. In the subsequent resolution of 7 by formation of the diastereomeric quinine salts, water was also found to be deleterious, as hydrated diastereomeric salts formed and gave no resolution. The selective crystallization of the desired salt 8 was driven by the formation of the iPrOH solvate, which crystallized faster than the undesired diastereomeric salt. 

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