6.13.1 Molecular and ionic structure and physical properties of amino acids
Amino acid molecules have at least one amino/amino group (-NH2) and
one carboxylic acid group (COOH).
The primary suffix name for an aliphatic carboxylic acid
is based on the "longest carbon chain name *" for the -COOH bond
system e.g. ethanoic acid, propanoic acid etc. The amino group
-NH2, with its C-atom position number, is added as a prefix. [*
without the end 'e']
They are usually colourless crystalline solids at room temperature.
Data on some of the simplest amino acids is quoted below.
(Mpt. = melting point; dec. = decomposes;
sub. = sublimes)
|IUPAC systematic name of amino acid
(common trivial name)
||Molecular form and the isomeric zwitterion
form (see notes below table)
||Comments including solubility
||Very soluble in water, the simplest amino
||Moderately soluble in water,
an α amino acid.
β alanine are structural positional isomers.
Moderately soluble in water, ,
a β amino acid. The simplest
amino acid to exhibit R/S stereoisomerism. The middle carbon is 'chiral' - 4 different groups attached.
||Soluble in water.
Soluble in water.
Note the presence of a sulfur
based functional group HS-.
Notes on the
(i) For the size of the molecule (e.g. as measured in electrons) they have
relatively high melting points, at which they sometimes thermally degrade
and decompose - this indicates strong intermolecular bonding of some form
between the amino acid molecules.
(ii) The intermolecular forces, apart from the 'usual' instantaneous dipole -
induced dipole forces, are greatly increased by hydrogen bonding or ionic
attraction between zwitterions (see below for their structure)..
(iii) The α and β (alpha and beta)
refer to the second and third carbon atoms to which the amino group can
be a substituent.
(iv) All the above have one -COOH group and one -NH2 group
in the molecule, so the aqueous solution will tend to be neutral ~pH 7.
See amino acid examples in
section 6.13.3 which
are not neutral.
There many amino acids essential to life and are found combined together
in proteins e.g tissue, enzymes.
Amino acids are the building blocks for these substances form long
chains called polypeptides.
Amino acids and
Amino-acids in aqueous solution, or in the
crystalline state, exist as 'zwitterions' where the proton migrates from the
acidic carboxylic -COOH group to the basic -NH2 amino group to form
the ionic groups -NH3+ and -COO–
BUT within the same 'molecule'.
For the functional groups present in the molecule, the carboxylic acid is
weakly acidic and amino group is weakly basic.
This results in an equilibrium between the neutral molecular form and
the zwitterion ionic
forms (shown above).
For example, shown as structural formulae of the molecule and
zwitterion AND the skeletal formulae of the molecule and zwitterion forms of ...
2-aminopropanoic acid , , AND ,
There is a strong electrical attraction between the oppositely charged ends of
6.13.2 A laboratory synthesis of amino acids from
halogenated carboxylic acids
(not a biosynthesis method)
This is the nucleophilic substitution by ammonia of the halide atom in
e.g. chloroethanoic acid + ammonia ===> aminoethanoic
acid + ammonium chloride
+ 2NH3 ===> H2NCH2COOH
A two stage synthesis of the amino acid alanine
2-aminopropanoic acid (the amino acid
alanine) when extracted from broken down protein will show optical
activity because it will consist of only one of the optical isomers, as
it was produced, and used in protein formation, by stereospecific
enzymes. It can be produced in the laboratory/industry by a two stage
+ Cl2 ===> CH3CHClCOOH + HCl
free radical chlorination of
propanoic acid (no optical isomers) with chlorine/uv gives
2-chloropropanoic acid which does exhibit optical isomerism (the
reaction also forms isomeric 3-chloropropanoic acid).
CH3CHClCOOH + 2NH3
===> CH3CH(NH2)COOH + NH4+
treating 2-chloropropanoic acid
with excess conc. ammonia gives 2-aminopropanoic acid, which again,
can exhibit optical isomerism.
In practice this kind of laboratory synthesis yields
a racemic mixture, a 50 : 50 mixture of the R and S stereoisomers.
In stage (1) the chlorine
radical could abstract/substitute either of the two middle H's with
equal probability and therefore a racemic mixture is likely to result.
OR if stage (2) went via a
carbocation (with a trigonal planar bond arrangement, SN1
mechanism), substitution can take place by the NH3 molecule hitting
either side of the carbocation 'centre' with equal probability.
Therefore either step could give an
equimolar mixture of the possible optical isomers.
For more details on reaction (2) see
carbocation mechanisms of haloalkane substitution reactions,.
Most synthetic amino acids are produced by complex biosynthetic pathways.
6.13.3 The multi-functional group chemistry of amino acids
The acidic and basic character of the -COOH and -NH2 functional
Amino acids are carboxylic acids
(like ethanoic acid, with the -COOH group) but commonly, one of the hydrogen atoms of the 2nd carbon atom is substituted with an
amino/amine group (a nitrogen + two hydrogens gives -NH2).
-COOH is a weakly acid carboxylic acid functional group in aqueous
R-COO-(aq) + H3O+(aq)
-NH2 is a weakly basic functional group in aqueous
R-NH3+(aq) + OH-(aq)
R is the 'rest of the molecule' and the two groups can cancel each
other out to give a ~neutral solution.
hydrogen on the same 2nd carbon can be substituted with other groups of
atoms (R) to give a variety of amino acids.
The simplest is aminoethanoic acid or 'Glycine'
another amino acid called 2-aminopropanoic acid or 'Alanine'
All amino acids have the general structure H2N-CH(R)-COOH
(see diagram by 5b heading).
R can vary, think of it as the 'Rest of the
R = H for Glycine, R = CH3 for
Amino acids have 2 functional groups:
-COOH carboxylic acid
BUT, there is the added complication of zwitterion form of the amino acid
e.g. for alpha-amino acids.
A flavour of the dual
chemistry - I'm giving the equations using both the 'molecular' and
(i) Reaction with a stronger acid, amino acid acts as a base
The amine group is protonated giving an alkylammonium ion
Here the -COO- group acts as the conjugate of the
carboxylic acid -COOH.
You reverse the reaction by adding alkali
(ii) Reaction with a stronger base, amino acid acts as an acid
RCH(NH2)COO-(aq) + H2O(l)
The carboxylate anion is formed
RCH(NH2)COO-(aq) + H2O(l)
Here the protonated zwitterion acts as a conjugate acid via the -NH3+
(This is just like the ammonium ion, NH4+ which
is the conjugate acid of the base ammonia NH3).
You reverse the reaction by adding acid
(iii) Things get a bit more tricky when there are two -COOH or two -NH2
groups in the molecule e.g. several in the table below
|Common name of amino acid
||IUPAC systematic name of amino
acid (allowed alternative)
||Molecular form and the isomeric zwitterion
|Will be weakly acidic in aqueous
Will be weakly acidic in aqueous solution.
Will be weakly alkaline in aqueous solution.
If there is one -COOH group and one -NH2 group in the moleule,
the aqueous solution will tend to be neutral ~pH 7.
If there are two -COOH groups and one -NH2 group, the aqueous
solution will tend to be weakly acid with a pH <7
If there is one -COOH group and two -NH2 group, the aqueous
solution will tend to be weakly alkaline with a pH >7.
6.13.4 The formation of polypeptides
Amino acids can polymerise together, by condensation
polymerisation, forming polypeptides.
The peptide linkage is formed by
elimination of water between two amino acids.
The simplest amino acid is glycine H2NCH2COOH
and the polymerisation can be written as ...
n H2NCH2COOH ===>
(-NHCH2COO-)n + nH2O,
where n can be quite a large
number in the polymer.
These polymers are therefore 'polyamides' as well as 'polypeptides'.
In general the polymerisation to form a
polypeptide/secondary amide link is ...
+ H2N-CH(R)-COOH ==> H2N-CH(R)-CO-HN-CH(R)-COOH
+ H2O ...
... to form one peptide linkage, so ...
==> -NH-CO-CH(R)-NH-CO-CH(R)-NH-CO-CH(R)-NH-CO-CH(R)- etc. n units long
... where R is variable chemical group, as there
over 20 known amino acids,
and so proteins are long chain polypeptides
and are natural
condensation polymers of amino acids.
Long chain polypeptides are what make the majority of the molecular
structure of proteins.
Each polypeptide, protein, enzyme etc. has its
own unique sequence of amino acids (all encoded for in an organism's DNA).
Diagram showing the formation of the
polyamide/polypeptide link as a water molecule is eliminated when the
carboxylic acid of one amino acid, and the amino group condense together to
give an polypeptide/amide link.
this case two amino acids have a formed the simplest possible polypeptide -
a simple dipeptide.
Note that at each end of the molecule,
on left) and the carboxylic
acid group (-COOH,
on right) can both form a bond with another amino acid molecule by
further elimination of water molecules.
So, both functional groups are involved in the condensation
to form the polymer.
So, if the process continues, as shown
below), you build up a long chain polymer - known as a polyamide,
polypeptide or a protein - they are all the same here.
Proteins have the same
(amide) linkages as nylon but with different units.
Proteins are an important component of
tissue structure and enzymes (powerful biological chemical catalysts) are
also protein molecules.
Proteins tend to adopt a particular three dimensional shape (3D) which aids
Apart from the structural proteins in you body e.g. muscle
tissue, enzymes are protein molecules wrapped into a specific 3D shape to carry
out their catalytic function.
For more detailed notes see
Enzymes and Biotechnology
When proteins are heated with aqueous
hydrochloric acid or sodium hydroxide solution they are hydrolysed to amino acids.
below, about how amino acids are identified in proteins.
There are 20 amino acids that make up the proteins in the
12 can be synthesised by us from other amino acids,
6.13.5 Amino acids from proteins and R/S
All the alpha-amino acids obtained from proteins are
optically active except glycine (aminoethanoic acid), that is they exhibit
R/S stereoisomerism (pin-pointed in the diagram above) where you have two
mirror image forms that cannot be superimposed on each other (as with
your right and left hands!).
R/S stereoisomerism page
2-aminoethanoic acid, H2NCH2COOH,
is not an optically active molecule because it
has no chiral/asymmetric carbon atom
because there is no carbon with 4 different groups attached, but all the
other alpha-amino acids have four different groups attached to the 2nd
carbon atom i.e. R-CH(NH2)COOH
In aqueous solution, and in the
solid state, they predominantly exist as zwitterions, the ionic form
derived from proton transfer from the carboxylic group onto the amino
Even so, the zwitterions will also exhibit R/S
stereoisomerism as well as the non-ionic molecular form.
R/S isomers of the non-ionic molecular form (R = CH3
R/S isomers of the ionic zwitterion form (R = CH3
need zwitterion form too
Comparing 'natural' and
'laboratory' synthesised amino acids (other than
When molecules capable of exhibiting
optical isomerism are obtained from natural sources, they usually
consist of one of the possible isomers (one of the enantiomers).
On extraction, purification and isolation, they show optical
activity (that is rotating the plane of polarised light in a polarimeter
This is due to the need for stereospecific structures from
enzymes to proteins.
The '3D' stereospecificity of enzyme
sites is discussed in section 6.
However, when the same compound is
synthesised in the laboratory by a non-biosynthetic route, it often consists of an equimolar
mixture of the two optical isomers (R/S isomer enantiomers).
This is known as a racemic
mixture and it is optically inactive due to one isomer cancelling
out the optical effect of the other.
It is wrong to say that R/S optical isomers are not, or cannot be formed,
in a laboratory synthesis!
Its difficult, but no
impossible, using very sophisticated synthesis techniques.
The most common explanation for the
production of a racemic mixture lies in understanding the mechanisms of
the laboratory synthesis reactions.
For example, if a carbocation is
formed, which has three C-R bonds in a trigonal planer arrangement, the
reagent molecule or ion (electron pair donor) can attack on either side
with equal probability.
So when a possible chiral carbon molecule is
formed in many a laboratory synthesis, it tends to be an equimolar
mixture of the two spatial possibilities or enantiomers.
carbocation mechanisms of haloalkane substitution reactions,
addition reactions of aldehydes/ketones.
However, since the 1990's the problem
is being tackled by the use of
Chromatography - a method of amino acid
means breaking down a
molecule with water to form two or more products.
Hydrolysis is accelerated if the substance is heated with acid or alkali solutions.
When proteins are heated with aqueous acid
they are hydrolysed to amino acids.
Paper chromatography or thin layer chromatography is used to separate
coloured compounds (illustrated above).
Thin layer chromatography (TLC) uses a stationary
phase of either silica gel or aluminium oxide immobilised on a flat
inert surface that can be made of glass or plastic.
In the procedure:
(1) samples spotted onto start
line, paper placed in solvent, but below start line of pencil.
(2) Solvent rises up paper.
(3) When solvent near top of
paper, remove paper to dry. For colourless amino acids, you spray the paper
with ninhydrin which gives a purple spot for each amino acid.
(4) You can then measure the Rf
values to identify amino acids in the mixture.
To illustrate the method I've
described the separation of coloured dye molecules to represent different
1 to 5 represent five pure compounds, 6 is a
Red, brown and blue make up the mixture because its spots
horizontally line up with the three known colours.
The substances (solutes)
to be analysed must dissolve in the solvent, which is called the mobile phase because it moves.
The solvent may be water or other suitable solvent that
the amino acids will dissolved in - can vary the pH of the eluent
solvent - the liquid that moves up the paper or TLC plate.
The paper or thin layer of
material on which the separation takes place is called the stationary or
immobile phase because it doesn't move.
The distance a substance
moves, compared to the distance the solvent front moves (top of grey area on
diagram 2) is called the reference or Rf value (a simple
ratio) and has a
value of 0.0 (not moved - no good), to 1.0 (too soluble - no good either).
Rf ratio values between 0.1 and 0.9 can be useful for analysis and
identification of the amino acids.
distance moved by dissolved substance (solute) / distance moved by solvent
However, amino acids are colourless,
but can still be separated in this way, so read on!
Thin layer or paper chromatography
can still used
to separate and identify the products of hydrolysis of
proteins because you make them coloured by using another
The hydrolysis can be done by boiling-refluxing the protein with hydrochloric acid.
The hydrolysed mixture is then 'spotted'
onto the pencil base line of the chromatography paper or the TLC plate.
Known amino acids are also
spotted onto the base line too.
The prepared paper is then placed
vertically in a suitable solvent, which rises up the paper/TLC plate.
Since the products are colourless, the
dried chromatogram is treated with another chemical to produce a
A reagent spray of Ninhydrin produces purple spots with
Using known amino acid samples, you can then tell which amino acids made
up the protein that you hydrolysed.
The number of different spots tells
you how many different amino acids made up the protein or peptide.
Spots which horizontally match the
standard known molecule spots confirm identity their identity.
The multi-functional group chemistry of amino
reactions of the carboxylic acid and amino (amine) functional groups
The acidic and basic character of the -COOH and -NH2 groups
has been dealt with in
Other reactions of the carboxylic acid group
Amino acids can be reacted with alcohols to form
esters using a strong acid catalyst like concentrated sulfuric acid
RCH(NH2)COOH + R'OH
The strong acid ensures the amino acid is protonated
and can undergo esterification.
The zwitterion form of the amino acid cannot be
reactions of the amine/amino acid group
Amino acids will react with acid chlorides and acid
anhydrides to replace one of the hydrogens on the amino group with
an acyl group (R-C=O, RCO) e.g.
RCH(NH2)COOH + R'COCl
The product is a secondary amide, but still with a
carboxylic acid group.
(b) Acting as a nucleophile in nucleophilic substitution reactions
The zwitterion nature of amino acids means that the
lone pair of electrons on the nitrogen is not available to allow the
amino acid to act as a nucleophile unless the pH is much higher than
7 i.e. via reaction (i) below
RCH(:NH2)COO- + H2O
The allows the amine group to acts as the 'front
end' of an electron pair donating nucleophile (: in the
The amino acid can then react with halogenoalkanes
to yield a secondary amine, albeit with a carboxylic acid group
retained. (X = Cl, Br or I)
2RCH(NH2)COO- + R'X +
RCH(NHR')COOH + RCH(NH3+)COOH
+ X- + 2OH-
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