Zwitterions and Dipoles

Amino acids, peptides, and proteins typically contain both acidic and basic functional groups such as carboxyl and amino groups. CarboxyHc acids with a pK of 5 can easily protonate an amine (pKj, 4) in aqueous solution, and therefore molecules containing both carboxyl and amino groups are found to be zwitterions 

The physical properties of crystalline amino acids are consistent with their existence as zwitterions. Their melting points are relatively high, often above 200 °C (392 °F), and they are far more soluble in water than in nonpolar solvents such as ether or chloroform. Measured dipole moments for crystalline amino adds are fairly large, reflecting the significant degree of charge separation. 

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 

Electrically neutral molecules carrying a positive and a negative charge in one of their major canonical descriptions are also called as dipolar species. In most dipolar 

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There are many other kinds of reactive intermediates, which do not fit into the previous classifications. Some are simply compounds that are unstable for various possible reasons, such as structural strain or an unusual oxidation state, and are discussed in Chapter 7. This book is concerned with the chemistry of carbocations, carbanions, radicals, carbenes, nitrenes (the nitrogen analogs of carbenes), and miscellaneous intermediates such as arynes, ortho-quinone methides, zwitterions and dipoles, anti-aromatic systems, and tetrahedral intermediates. This is not the place to describe in detail the experimental basis on which the involvement of reactive intermediates in specific reactions has been estabhshed but it is appropriate to mention briefly the sort of evidence that has been found useful in this respect. Transition states have no real hfetime, and there are no physical techniques by which they can be directly characterized. Probably one of the most direct ways in which reactive intermediates can be inferred in a particular reaction is by a kinetic study. Trapping the intermediate with an appropriate reagent can also be very valuable, particularly if it can be shown that the same products are produced in the same ratios when the same postulated intermediate is formed from different precursors. 

Merocyanine dyes 50-55 (Fig. 5.18) possess an electronic structure at the meso-meric center between neutral and zwitterionic electron distribution and have high polarizabilities and dipole moments and exhibit absorption spectra with sharp bands that give rise to exceptionally brilliant magenta hues [60],... 

Gutowski M, Skurski P, Simons J (2000). Dipole-bound anions of glycine based on the zwitterion and neutral structures. J Am Chem Soc 122 10159-10162. 

Examples of 1,3-dipoles include diazoalkanes, nitrones, carbonyl ylides and fulminic acid. Organic chemists typically describe 1,3-dipolar cycloaddition reactions [15] in terms of four out-of-plane 71 electrons from the dipole and two from the dipolarophile. Consequently, most of the interest in the electronic structure of 1,3-dipoles has been concentrated on the distribution of the four Jt electrons over the three heavy atom centres. Of course, a characteristic feature of this class of molecules is that it presents awkward problems for classical valence theories a conventional fashion of representing such systems invokes resonance between a number of zwitterionic and diradical structures [16-19]. Much has been written on the amount of diradical character, with widely differing estimates of the relative weights of the different bonding schemes. 

The Ionization of Amino Acids, The Zwitterion or Dipole Ion. As is well known amino adds are of importance in that they are the structural units from which proteins are formed, and into which food proteins break down during digestion. The simplest compound of the series is glycine, NHaCH2COOH, which like all other amino adds contains an amino and a carboxyl group. The type formula for the series may thus be represented by NH2RCOOH. Amino acids are able to combine with both adds and bases, i.e., they are amphoteric. 

Hydrogen isocyanide (HNC) is a linear triatomic molecule with Coov point group symmetry. It is a zwitterion and an isomer of hydrogen cyanide (HCN). Both HNC and HCN have large, similar dipole moments, with respectively phnc=3.05 Debye and... 

Examine the charge on the methylidene group, as well as the magnitude and direction of the molecule s dipole moment. Are they consistent with representation of the ylide as a hypervalent molecule or as a zwitterion ... 

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-... 

The ultraviolet spectra of the pyridinecarboxylic acids (334) were initially interpreted assuming that the proportion of the zwitterion structure 335 was not appreciable,and the early pK work was inconclusive. However, Jaffe s calculations based on the Hammett equation indicated that about 95% of nicotinic and isonicotinic acids existed in the zwitterion form, and ultraviolet spectral data showed that the actual percentages of picolinic, nicotinic, and isonieotinie acids existing in the zwitterion form in aqueous solution are 94, 91, and 96%, respectively.This was later confirmed by Stephenson and Sponer, who further demonstrated that the proportion of the zwitterion form decreases in solvents of low dielectric constant, becoming very low in ethanol. Dipole moment data indicate that isonicotinic acid exists as such in dioxane, and 6-hydroxypyridine-3-carboxyiic acid has been shown to exist in form 336 u.sing pK data. ... 

Amino acid zwitterions are internal salts and therefore have many of the physical properties associated with salts. They have large dipole moments, are soluble in water but insoluble in hydrocarbons, and are crystalline substances with relatively high melting points. In addition, amino acids are amphiprotic they can react either as acids or as bases, depending on the circumstances. In aqueous acid solution, an amino acid zwitterion is a base that accepts a proton to yield a cation in aqueous base solution, the zwitterion is an add that loses a proton to form an anion. Note that it is the carboxylate, -C02-, that acts as the basic site and accepts a proton in acid solution, and it is the ammonium cation, -NH3+, that acts as the acidic site and donates a proton in base solution. 

The problem of the structure of 1,2- and 1,4-quinone diazides was investigated by Le Fevre s group (1949, 1954) by measuring dipole moments. The observed moments in benzene are in the range 2.9 to 5.0 D, compared with calculated values of 1.6 to 4.0 D for the quinone diazide structure and 15.7 and 27.4 D respectively for the 1,2-and 1,4-zwitterionic forms. No attempts were made by Lowe-Ma et al. (1988) to calculate dipole moments for the mesomeric structure 4.4 that they proposed. 

Olefins (enamines) unsymmetrically substituted with strong electron-donating (amino) group and CS generate zwitterions (1,4-dipoles) [32, 33]. Polar additions are proposed here to be reactions in the pseudoexcitation band. 

Typical examples are the conversion of the neutral form of an amino acid into its zwitterionic form, the helix-coil transitions in polypeptides and polynucleotides, and other conformational changes in biopolymers. Reactions of higher molecularity in which reactants and products have different dipole moments are subject to the same effect (association of the carboxylic acids to form hydrogen-bonded dimers). Equilibrium involving ions are often more sensitive to the application of an electric field ... 

Karelson et al. [268] used the AMI D02 method with a spherical cavity of 2.5 A radius to study tautomeric equilibria in the 4-hydroxyisoxazole system (they did not specify which hydroxyl rotamer they examined). Tautomer 17 predominates in aqueous solution. Although AMI predicts 16 to be about 10 kcal/mol more stable in the gas-phase than 17, its dipole moment is only predicted to be 0.68 D. Tautomer 17 has a predicted dipole moment of 2.83 D in the gas-phase. With the small cavity, the two dipole moments increase to 0.90 and 4.56 D, respectively, and this is sufficient to make 17 0.3 kcal/mol more stable than 16 in solution. Zwitterion 18 is much better solvated than either of the other two tautomers, but AMI predicts its gas-phase relative energy to be so high that it plays no equilibrium role in either the gas phase of solution. 

Figure 1.12 Reichardt s betaine dye in its zwitterionic ground state (a) and first excited state (b). The ground state has a larger dipole moment (15 D) than the excited state (6 D). Measurement of the energy of the transition between these two states (n - n ) is the basis for the Ej scale of solvent polarity...

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