Proton amino acids

To recognize a chiral ammonium guest, binaphthyl hinge crowns were designed and proved the enantiomeric separation of protonated amino acid ester racemates [21]. A series of chiral azophenol acerands incorporating one or two optically active hydrobenzoin unit, 51-58, has been synthesized to study the title theme, enantiomer selective coloration with chiral amines. 

The fragmentation of protonated amino acids was the subject of several early investigations [238-240]. The most pronounced reaction is loss of the elements C02H2. Detailed quantum chemical calculations of the potential energy hypersurface of protonated glycine demonstrated that the sequence of events preceding this dissociation are [231,241,242] ... 

Because a protonated amino acid has at least two dilfeent protons that can be removed, a value is reported for each of these protons. For example, the p/fg of the carboxy proton of alanine is 2.35 and the pATa of the ammonium proton is 9.87. Table 28.1 lists these values for all 20 amino acids. 

Carbodiimides are known to react with primary amines to form guanidines.f In the case of amino acid esters, a subsequent elimination of alcohol is possible with formation of an imino-hydantoin species (Scheme 8). However, these reactions usually require higher temperatures or the occurrence of acid catalysis and therefore can be neglected when unprotonated amino acid derivatives are acylated using carbodiimides. On the other hand, this side reaction becomes more important when protonated amino acids (i.e., amino acid ester hydrochlorides) are coupledf and these byproducts may occur. 

The pf of amino acids is the pH at one equivalence point along the titration curve, specifically the equivalence point at which all the AA" is converted to AA . The pH at this point is, as usual, the average of the pK value to follow and the p/fo value just passed. Similarly, pH, is the pH at one equivalence point and may be similarly calculated. To determine pJ and pH simply sketch the titration curve and indicate the predominant ionic species present at each key point, Or, prepare a table showing the ionic form of each titratable group at key points. For simplicity, assume that you are starting with the maximally protonated amino acid or peptide. 

The simplest acids containing the NH3" group are the protonated amino acids such as the protonated form of glycine, " "NH3CH2COOH, or the protonated form of amino acid esters such as NH3CH2COOCH3. There are more complex amino acids which can have protonated amino acid groups, such as histidine, below. 

The most easily protonated amino acid is arginine due to the resonance stabilized species that is formed. Protonation occurs at the imino nitrogen (HN=). The resonance stabilization of the resulting species is shown as ... 

Cram and coworkers developed a convenient extraction method that they used to assess the structural factors that influence complexation of metal ions and protonated amino acids. (For a review of chiral complexation see Ref. [29].) The method was used extensively enough to merit a description here. An aqueous solution of, for example, sodium picrate, is prepared. The solution is yellow owing to the trinitrophenoxide anion. A potential host molecule is dissolved in CHCI3, and the two phases are shaken together. If successful, the host molecule will extract the cation picrate salt into the organic phase. The extent of the extraction can be quantitated by UV spectroscopy, based on the assumption that the amount of picrate anion observed corresponds to the amount of cation extracted. For obvious reasons, this method is called the "picrate extraction technique." For comparisons to be made between data sets obtained by this method, solvents, volumes, concentrations, temperatures, etc., must be controlled. The influence of the anion on complexation was also studied. ... 

Harrison, A.G., Yalcin, T. (1997) Proton mobility in protonated amino acids and peptides. Int J Mass Spectrom Ion Processes, 165-166, 339-347. 

Consider the fully protonated amino acid valine ... 

One such nonnatural function of natural ionophores is the complexation of organic ammonium cations for example, protonated amino acid esters. Since natural ionophores are chiral compounds, the process can be enantioselec-tive. Binding of ammonium cations by such receptors as monensin or lasalocid (Fignre 1) is efficient bnt lack the expected enantioselectivity. However, cyclic or podand-type derivatives of monensin like 1 or 2 (Figure 1) show significant enantioselectivity the ratios of binding constants of the R and S enantiomers of protonated methyl esters of phenylglycine, phenylalanine, and leucine to 2 are A r/ZCs = 5.1, 6.2, and 7.6, respectively. Crown-ether type derivatives like 1 show lower enantioselectivities. 

Acidity of an a-Carboxyi Group (Section 27.2A) An a-COOH pK approximately 2.19) of a protonated amino acid is a considerably stronger acid than acetic acid 4.76) or other low-molecular-weight aliphatic carboxylic acid, owing to the electron-withdrawing inductive effect of the a-NHj+ group. 

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