Amino Acids: Structure, Properties and Optical Isomerism

1A solid that should be a liquid

Glycine, propanoic acid and butan-1-amine have almost the same molar mass, about 74 g mol⁻¹. Propanoic acid and butan-1-amine are liquids at room temperature. Glycine is a white crystalline solid that does not melt at all: it chars and decomposes at about 233 °C. It dissolves well in water but hardly at all in hexane. These are the properties of an ionic compound, yet glycine is a small organic molecule with no metal in it. The explanation is that glycine carries an acid group and a base group in the same molecule, and they react with each other.

2The general structure and common examples

About twenty 2-amino acids are coded by genes and built into proteins; they differ only in R. Table 9.3 shows eight of them, with their three-letter codes.

Table 9.3: Eight protein amino acids. pI values from the $\mathrm{p}{K}_a\backslash mathrm\{p\}K\_a$ data in Lehninger, Principles of Biochemistry.

3Amino acids compared with carboxylic acids and amines

In the solid and in neutral water the –COOH group gives its proton to the –NH₂ group of the same molecule:

$${\mathrm{H}}_2\mathrm{N}-\mathrm{C}{\mathrm{H}}_2-\mathrm{C}\mathrm{O}\mathrm{O}\mathrm{H}\to {\mathrm{H}}_3{\mathrm{N}}^{+}-\mathrm{C}{\mathrm{H}}_2-\mathrm{C}\mathrm{O}{\mathrm{O}}^{-}\backslash mathrm\{H\_2N\{-\}CH\_2\{-\}COOH\; \backslash rightarrow\; H\_3N^\{+\}\{-\}CH\_2\{-\}COO^\{-\}\}$$

So an amino acid has the high melting point and water solubility of a salt, and it is amphoteric: it reacts with both acids and bases.

4The effect of pH

Figure 9.3: Adding acid protonates the carboxylate; adding alkali removes a proton from $-\mathrm{N}{\mathrm{H}}_3^{+}\backslash mathrm\{-NH\_3^\{+\}\}$. At the pI the zwitterion dominates.

For an amino acid with an uncharged side chain, the pI lies halfway between the $\mathrm{p}{K}_a\backslash mathrm\{p\}K\_a$ of the –COOH group and that of the $-\mathrm{N}{\mathrm{H}}_3^{+}\backslash mathrm\{-NH\_3^\{+\}\}$ group. In electrophoresis, a mixture is placed on a gel or paper soaked in a buffer between two electrodes: amino acids that are positive at that pH move to the cathode, negative ones to the anode, and those at their pI stay put. Spraying with ninhydrin then shows each amino acid as a purple spot.

5Chemical properties

• With acids: ${\mathrm{H}}_3{\mathrm{N}}^{+}\mathrm{C}{\mathrm{H}}_2\mathrm{C}\mathrm{O}{\mathrm{O}}^{-}+{\mathrm{H}}_3{\mathrm{O}}^{+}\to {\mathrm{H}}_3{\mathrm{N}}^{+}\mathrm{C}{\mathrm{H}}_2\mathrm{C}\mathrm{O}\mathrm{O}\mathrm{H}+{\mathrm{H}}_2\mathrm{O}\backslash mathrm\{H\_3N^\{+\}CH\_2COO^\{-\}\; +\; H\_3O^\{+\}\; \backslash rightarrow\; H\_3N^\{+\}CH\_2COOH\; +\; H\_2O\}$.
• With alkalis: ${\mathrm{H}}_3{\mathrm{N}}^{+}\mathrm{C}{\mathrm{H}}_2\mathrm{C}\mathrm{O}{\mathrm{O}}^{-}+\mathrm{O}{\mathrm{H}}^{-}\to {\mathrm{H}}_2\mathrm{N}\mathrm{C}{\mathrm{H}}_2\mathrm{C}\mathrm{O}{\mathrm{O}}^{-}+{\mathrm{H}}_2\mathrm{O}\backslash mathrm\{H\_3N^\{+\}CH\_2COO^\{-\}\; +\; OH^\{-\}\; \backslash rightarrow\; H\_2NCH\_2COO^\{-\}\; +\; H\_2O\}$; with sodium hydroxide this gives the salt sodium aminoethanoate.
• Esterification of the –COOH group, heating with an alcohol and a strong acid catalyst: glycine and ethanol give ethyl aminoethanoate, ${\mathrm{H}}_2\mathrm{N}\mathrm{C}{\mathrm{H}}_2\mathrm{C}\mathrm{O}\mathrm{O}\mathrm{C}{\mathrm{H}}_2\mathrm{C}{\mathrm{H}}_3\backslash mathrm\{H\_2NCH\_2COOCH\_2CH\_3\}$ (isolated as its hydrochloride).
• Acylation of the –NH₂ group by an acyl chloride, as for any amine, giving an amide.
• With nitrous acid, the primary amino group releases nitrogen gas: ${\mathrm{H}}_2\mathrm{N}\mathrm{C}{\mathrm{H}}_2\mathrm{C}\mathrm{O}\mathrm{O}\mathrm{H}+\mathrm{H}\mathrm{N}{\mathrm{O}}_2\to \mathrm{H}\mathrm{O}\mathrm{C}{\mathrm{H}}_2\mathrm{C}\mathrm{O}\mathrm{O}\mathrm{H}+{\mathrm{N}}_2+{\mathrm{H}}_2\mathrm{O}\backslash mathrm\{H\_2NCH\_2COOH\; +\; HNO\_2\; \backslash rightarrow\; HOCH\_2COOH\; +\; N\_2\; +\; H\_2O\}$. Measuring the volume of ${\mathrm{N}}_2\backslash mathrm\{N\_2\}$ is a classic way to find the amount of amino groups.
• Condensation with another amino acid to form a peptide bond: Lesson 4.

6Optical isomerism

In every protein amino acid except glycine, the α-carbon carries four different groups, H, $\mathrm{N}{\mathrm{H}}_2\backslash mathrm\{NH\_2\}$, COOH and R, so it is a chiral centre and the amino acid exists as two enantiomers (Figure 9.4). Glycine, with R = H, has two identical H atoms on the α-carbon and is not chiral.

Figure 9.4: The enantiomers of alanine. No rotation can lay one exactly on the other, just as a left hand cannot fit a right glove.

Enantiomers have the same melting point, solubility and chemical reactions with non-chiral reagents. They differ in two ways: they rotate plane-polarised light by equal angles in opposite directions, and they behave differently with other chiral molecules, such as the enzymes and receptors in your body. An equimolar mixture, a racemic mixture, is optically inactive because the two rotations cancel. Proteins are built almost entirely from L-amino acids. The letters L and D describe the arrangement in space, not the direction of rotation; that is shown separately as (+) or (−).

Taste shows the difference. The sodium salt of L-glutamic acid, monosodium glutamate (flavour enhancer E621 on stock-cube labels), gives the savoury taste called umami; the D-enantiomer does not.