Zwitterionic structure of amino acid

Cation-TT interactions play a crucial role in molecular recognition. For example, Na /K cation interactions with aromatic rings of some amino acids are implicated in the biological functions of specific enzymes and in the selectivity of Na" /K channels. " The same factors are responsible of the relative stability of the charge-solvated vs. zwitterionic structure of amino acids. " ... 

We saw in Section 4.6.1 the use of zwitterionic hosts for anions in which the counter-cation is non-speciflcally bound on the outside of the molecule. We now turn to zwitterionic guests where the guest has both cationic and anionic parts. We have already described in Section 5.1.1 the zwitterionic structure of amino acids and amino acid binding has been a major part of the interest in the construction of hosts for zwitterions. An excellent example is compound 4.30 (Section 4.5) which is... 

In polar solvents, the structure of the acridine 13 involves some zwitterionic character 13 a [Eq. (7)] and the interior of the cleft becomes an intensely polar microenvironment. On the periphery of the molecule a heavy lipophilic coating is provided by the hydrocarbon skeleton and methyl groups. A third domain, the large, flat aromatic surface is exposed by the acridine spacer unit. This unusual combination of ionic, hydrophobic and stacking opportunities endows these molecules with the ability to interact with the zwitterionic forms of amino acids which exist at neutral pH 24). For example, the acridine diacids can extract zwitterionic phenylalanine from water into chloroform, andNMR evidence indicates the formation of 2 1 complexes 39 such as were previously described for other P-phenyl-ethylammonium salts. Similar behavior is seen with tryptophan 40 and tyrosine methyl ether 41. The structures lacking well-placed aromatics such as leucine or methionine are not extracted to measureable degrees under these conditions. 

All solid amino acids exist as dipolar ions known as zwitterions (Figure 1.2(a)). In aqueous solution the structure of amino acids are dependent on the pH of the solution (Figure 1.2(b)). The pH at which an aqueous solution of an amino acid is electrically neutral is known as the isoelectric point (pi) of the amino acid (Table 1.1). Isoelectric point values vary with temperature. They are used in the design of electrophoretic and chromatographic analytical methods for amino acids. 

Figure 1.2 (a) The general structural formula of the zwitterions of amino acids, (b) The structures of amino acids in acidic and basic aqueous solutions... 

Dipolar structure of amino acids—The dipole moment data support the dipolar, zwitterionic, structure of the amino acids, viz HgRGHCOO-. If the molecule at its iso-electric point possesses this structure, it will have a very large dipole moment of the order of 13 9 D since the distance between the charges is approximately 2-9 A. Unfortunately such compounds are only soluble in polar solvents and it is therefore impossible to measure the dipole moments directly. The dielectric constant of aqueous solutions of amino acids is, however, greater than that of water and furthermore increases in direct proportion to the concentration. The value of A el Ac... 

For most amino acids the R represents a complex organic group in glycine, the R represents H (hydrogen). Amino acids are usually known by their common rather than chemical names. For instance glycine, with the structural formula H2N-CH2-COOH, is known chemically as amino acetic acid. For a discussion of the structure of amino acids, consult Harbome (1984) and Bhushan and Martens (1996). In living aqueous systems, amino acids exist predominantly as dipolar ions referred to as zwitterions and represented by the formula... 

Since the aqueous solution-phase structure of amino acids and peptides is normally zwitterionic, while that in the gas phase is frequently non-charge-sepa-rated, there is considerable interest in whether, and how completely, the complexes... 

Schmidt J, Kass SR (2013) Zwitterion vs neutral structures of amino acids stabilized by a negatively charged site infrared photodissociation and computations of proline-chloride anion. J Phys Chem A 117 4863-4869... 

Although we usually write the structures of amino acids as neutral, their actual structure is ionic and depends on pH. In general, amino acids undergo an intramolecular acid-base reaction and form a dipolar ion, or zwitterion. 

Glycine (Gly) is the simplest molecule in the 20 amino acids, and the FUV spectrum of Gly is the most appropriate to show the electronic transition of the backbone structure of amino acids. The primary chromophore of Gly is the carboxyl group. Figure 4.13 shows the FUV spectra of 2 M Gly in 1.81 M H2SO4, pure water, and 3.36 M NaOH aqueous solutions. Because the pATai and pK 2 values of Gly are 2.34 and 9.60, the protonation states are ammonium carboxylic acid, zwitterion, and aminocarboxylate anion in acidic solution, pure water, and basic solution, respectively. The intense bands appear at 157.5 nm (molar absorption coefficient e = 5.15x10 M cm ), 168.9 nm (7.76x10 M cm ), and 169.9 nm (7.73 x 10 cm ) for the acid, the zwitterion, and the anion forms,... 

Figure 4.1 The zwitterionic structure of two ot-amino acids, and the condensation reaction to form a dipeptide, linked by a peptide bond.

Recognition of amino acids has been attempted more frequently with receptors that are likewise zwitterionic in nature (compare 35). Some early studies include the transport of phenylalanine by a merocyanine dye through a liposomal bilayer [53]. Rebek s dicarboxylate-complexing cleft 9 (see Sect. 2) turned out to be a selective (though achiral) binder of trypthophane, phenylalanine, and tyrosine methyl ether [54]. A reasonable structure for a phenylalanine complex of 2 1 stoichiometry, as deduced from NMR studies, is schematically represented in formula 39 [55]. 

In agreement with results reported by Shirahama and co-workers, the cis C-3/C-4 stereochemistry in products 167,26,168 and 169 could be diagnosed by the proton at C-4 appearing at lower field than for the corresponding trans cases 170 to 173.33,83 Further structural confirmation was obtained by X-ray crystallography on o-anisyl derivative 26 (Figure 14).84 This also confirmed the expected zwitterionic structure of the amino acid. 

The acid-base behavior of amino acids may also be illustrated via titration curves. If one started with aspartic acid hydrochloride, that is, aspartic acid crystallized from solution in hydrochloric acid, one would require 3 mol base to remove completely the protons from 1 mol aspartic acid. The titration curve obtained with structures at each step of the reaction series is shown in Figure 4.1. Note that the isoelectric point is attained after one proton equivalent has been removed from the molecule. At this point, aspartic acid contains one positive and one negative charge it is zwitterionic. 

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. 

Gorbitz, C.H. Structures and conformational energies of amino acids in the zwitterionic, hydrogen-bonded state, J. Mol. Struct. (Theochem) 775(1—3) (2006) 9—17. 

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