Zwitterion formation

Because of the zwitterion formation, mutual buffering action, and the presence of strongly acid components, soybean phosphoHpids have an overall pH of about 6.6 and react as slightly acidic in dispersions-in-water or in solutions-in-solvents. Further acidification brings soybean phosphoHpids to an overall isoelectric point of about pH 3.5. The alcohol-soluble fraction tends to favor oil-in-water emulsions and the alcohol-insoluble phosphoHpids tend to promote water-in-oil emulsions. 

Many of the properties oj -hydroxypyridines are typical of phenols. It was long assumed that they existed exclusively in the hydroxy form, and early physical measurements seemed to confirm this. For example, the ultraviolet spectrum of a methanolic solution of 3-hydroxypyridine is very similar to that of the 3-methoxy analog, and the value of the dipole moment of 3-hydroxypyridine obtained in dioxane indicates little, if any, zwitterion formation. However, it has now become clear that the hydroxy form is greatly predominant only in solvents of low dielectric constant. Comparison of the pK values of 3-hydroxypyridine with those of the alternative methylated forms indicated that the two tautomeric forms are of comparable stability in aqueous solution (Table II), and this was confirmed using ultraviolet spectroscopy. The ratios calculated from the ultraviolet spectral data are in good agreement with those de-... 

Figure 1. Titration curve of PATE illustrating zwitterion formation near isoprotic point.

The reaction of CS2 with diamines proceeds with CS2 addition at the less basic site, as the more basic site accepts the proton in the formation of the zwitterion. In the case of 0-aminoethylpiperazine, the primary amino group condenses with CS2 and the secondary amine undergoes zwitterion formation (254). 

Kensy et al. [1993] showed that the zwitterion formation and subsequent cyclization due to hydrogen transfer take place in the lowest triplet excited state of diphenylamine and its methyl substituents. The crossover temperature is about 100 K, and the values of C(H) are 10 2-10 4 s 1 for various substituents. The H/D kinetic isotope effect at T [Pg.177]

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]. 

Calculated from AGrds and AG lc. fA[Pg.212]

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. 

The decarboxylation of pyrazine-2,3-dicarboxylic acids may be carried out by heating in vacuo or in glacial acetic acid at 130°-145°,211 or by heating in a solvent of high dielectric constant such as nitrobenzene.212 It is suggested that these solvents promote decarboxylation by zwitterion formation. 

The most important competing process to the bond-formation is the complete electron transfer to form ion-radicals, which occurs where no bond formation is possible, for example, for aromatic donor-acceptor pairs. For vinyl copolymerizable pairs, the bond will form between the components to give a diradical tetramethylene. For the ionic homopolymerization system, on the other hand, it is difficult to distinguish the ion-radicals from zwitterionic tetramethylenes by the kinetic analysis. In this case, the accompanying cycloaddition reaction offers powerful evidence for the zwitterion formation, i.e., the bond-formation. 

C-H 0=C hydrogen bonds may inhibit zwitterion formation in the crystalline state. This suggestion has been made on the basis of isonicotinic acid [464], and of nicotinyl glycine [465]. In these crystal structures, the observed C-H 0=C interactions with H 0 distances from 2.35 to 2.66 A and C-ft 0 angles in the range 123 0 to 170° appear to be preferred and suppress the formation of the more common NH 0=0 bonds. Since, however, there is no evidence of this in the amino acid crystal structures, this effect, if real, must be associated with the properties of the pyridine ring. 

When the system is appropriately substituted, cycloaddition may even proceed via zwitterion formation [244] (Figure 7.73). 

Vinyl- and 4-vinylpyridines and 4-dimethylaminostyrene copolymerize with 2,4,6-trinitrostyrene without added initiator. The authors conclude that zwitterion formation is the first step. These copolymerizations seem to be analogous to those recently investigated by Saegusa and to be described later. 

The authors of the three publications, so far described, could not find any evidence for N-zwitterion formation. Kiinzel, Giefer, and Kem41) believe they have. This group measured the effectiveness of a wide range of covalent bases as initiators of formaldehyde polymerization. 

In addition to the chemical tests, measurements of the dielectric constant of polymerizing solutions also suggested zwitterion formation. With amine initiators, but not sodium acetate, the dielectric constant increased steadily with conversion. An approximate chain end to end distance was calculated from the increase in dielectric constant and it corresponded closely to the value expected for a random coil. 

In the absence of cocatalysis zwitterion formation is a reasonable postulate. 

Such a mechanism controls the stereochemistry of zwitterion formation by favouring the side-chain conformation (22) with... 

The arguments presented here are consistent with the latest observation [3ir] that the i7/ -methyl-i7a-etianate is the major product when the reaction is performed in a non-polar medium NaOMe in 1,2-dimethoxyethane). These conditions would be unfavourable to Zwitterion formation, but apparently permit the concerted formation of the cyclopropanone (20) by the route depicted (p. 209). 

The equilibrium constant for zwitterion formation (logATgq = -15.95) may be obtained from the equilibrium constant for formation of the neutral adduct (logA q = -13.39)" and the values of hydroxyl and imidazolyl of the adduct (8.12 and 5.56 respectively), which are determined by calculation. The decomposition rate constant Z aic can be determined for the putative zwitterion intermediate by combining the equilibrium constant and the observed rate constant (0.583 M" sec" ) to give 4.96 x 10 sec". This rate constant exceeds the value expected for a vibration (10 sec" ) and indicates that the intermediate cannot have a discrete existence and that the mechanism must be a concerted process enforced by the short lifetime of the intermediate. In other words the putative intermediate cannot pass enough reaction flux to support the observed reactivity. 

The chemical yields for both the zwitterions formation and acidification steps were essentially quantitative since neither reaction produced by-products the TSIL synthesis was 100% atom efficient. 

In theses reactions, the equilibrium constant for the formation of the anionic adduct (IX), which is the product of for zwitterion formation (equation 10) and Ka , the acid dissociation constant of the zwitterion,5 is abnormally low, particularly so for the benzylideneacetylacetone reaction (C. 

Despite excellent IV activity, enalaprilat has very poor oral bioavailability. Esterification of enalaprilat produced enalapril (Fig. 28.9), a compound with superior oral bioavailability. The combination of structural features in enalaprilat, especially the two carboxylate groups and the secondary amine, are responsible for its overall low lipophilicity and poor oral bioavailability. Zwitterion formation also has been suggested to contribute to the low oral activity (25), and a comparison of the pKa values for the secondary amine of enalaprilat and enalapril supports this explanation. Ionization of the adjacent carboxylate in enalaprilat greatly enhances the basicity of the secondary amine such that the pKa of the amine in this compound is 8.02, whereas in enalapril, it is only 5.49. Thus, in the small intestine, the amine in enalaprilat will be primarily ionized and form a zwitterion with the adjacent carboxylate, but the amine in enalapril will be primarily un-ionized (26). 

Martin RB, Zwitterion formation upcm deprotonaticHi in L-3,4-dihydroxyphenylalanine and other phenolic amines, /. Phy. Chem., 75,2657-2661 (1971). Qted in Szuiczewski DH, Hong W-H and Epinephrine, APDS, 7,193-229 (1978) ottier refierences were also given. 

Electrostatic Strong interaction between ions for charges and q, separated by r 2, and solvent dielectric constant, water has large g stabilizes zwitterion formation... 

The lack of evidence for the involvement of cofactors in ODCase catalyzed decarboxylation prompted Beak and Siegel to propose a novel mechanism, which was supported by experiments on model systems [5]. They showed that the decarboxylation of 1,3-dimethylorotic acid in sulfolane follows two different pH-dependent pathways. In neutral solution, decarboxylation is initiated by zwitterion formation. This led to the proposal of a zwitterion intermediate in the ODCase catalyzed reaction in which the 02 of the pyrimidine ring is protonated, promoting the release of CO2. 

While the naturally occurring amino adds are not zwitterions in the vapor phase, they are in aqueous solutions, implying that water plays an important role in indudng zwitterion formation. Together, these observations inspire the question. How many water molecules are required to induce zwitterion formation in a given amino add molecule Calculations suggest that five water molecules are needed to transform glycine into its zwitterion, while four each are required for phenylalanine and tryptophan. Since the excess electron may also make a... 

Figure 6.2 Pictorial representation of possible ODA interactions with oxidative acid purified SWNTs through (A) zwitterions formation and (B) physisorp-tion-assisted organization of ODA on SWNT sidewalls ...

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