Amino acid ionization state

The 20 natural amino acids differ from each other by the nature of their sidechains. Differences involve overall size, hydrophobic or hydrophilic character and, perhaps most importantly, ionization state. While the sidechains are normally written in terms of neutral structures, some may also exist in either protonated or deprotonated forms depending on pH. 

A selection of amino acids (acid A, acid B,...) terminated at both ends by amide functionality, i.e., MeNHCO-CHR-NHCOMe, are provided. These are given in the ionization states found at neutral pH. For each, first identify the amino acid, and then the ionization state (neutral, protonated or deprotonated). Next compare electrostatic potential maps among the different amino acids. Which amino acids would prefer hydrophobic environments Hydrophilic environments Explain your reasoning. 

Comparison of solution pH with the pKa of a side chain informs about the protonation state. A unique pKa, termed the standard or model pKa, can be experimentally determined for each ionizable side chain in solution when it is incorporated in a model compound, often a blocked amino acid residue [73] (Table 10-1). In a protein environment, however, the pKa value of an ionizable side chain can substantially deviate from the standard value, due to desolvation effects, hydrogen bonding, charge-charge, charge-dipole, and other electrostatic interactions with the... 

The most significant amino acids for modification and conjugation purposes are the ones containing ionizable side chains aspartic acid, glutamic acid, lysine, arginine, cysteine, histidine, and tyrosine (Figure 1.6). In their unprotonated state, each of these side chains can be potent nucleophiles to engage in addition reactions (see the discussion on nucleophilicity below). 

The ionic states at pH 7.0 of these amino acids with ionizable side-chains are shown below. 

Cardoso et al. [115] using the phase transfer technique studied the driving forces involved in the selective solubilization of three different amino acids having same pi, namely aspartic acid (hydrophilic), phenylalanine (slightly hydrophobic), and tryptophan (hydrophobic) in cationic TOMAC-RMs. The main driving forces involved were found to be hydrophobic and electrostatic interactions. Few other researchers have also identified that the major driving forces involved in the amino acid solubilization were hydrophobic interactions [ 114,159] and amino acid structure as well as its ionization state [160,161]. 

FIGURE 3-5 The 20 common amino acids of proteins. The structural formulas show the state of ionization that would predominate at pH 7.0. The unshaded portions are those common to all the amino acids the portions shaded in red are the R groups. Although the R group of... 

Ionization State of Amino Acids Each ionizable group of an amino acid can exist in one of two states, charged or neutral. The electric charge on the functional group is determined by the relationship between its pifa and the pH of the solution. This relationship is described by the Henderson-Hasselbalch equation. 

Normally, amino acids exist as dipolar ions. RCH(NH,+ iCOO-. in a neutral state, where both amino and carboxyl groups are ionized. The dipolar form, RCH(NH2)COOH may be considered, but the dipolar form predominates for the usual monoamino monocarboxylic acid and it is estimated that these forms occur 10s to 106 times more frequently than the non-polar forms. Amino acids decompose thermally at what might be considered a relatively high temperature (200-300°C). The compounds are practically insoluble in organic solvents, have low vapor pressure, and do not exhibit a precisely defined melting point. 

Amino acid esters can be monodentate (1) or bidentate (2), and examples of both types of complex have been isolated and their solid state IR spectra studied.39 41 Many investigations have shown that formation of the monodentate ester species has similar effects to protonation of the a-amino group. Thus the pKa values of MNH2CH(R)C02H and NH3CH2C02H (carboxyl ionization) are usually quite similar.42... 

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