In this topic you will learn about naming molecules, the acid / base behaviour in aqueous solutions, the reactions of amino acids to form peptides or proteins and the phenomena of optical isomerism.
Student Activity 1
Here are three structures of amino acids.
glycine
phenylalanine proline
a) Make a model of glycine (one each);
b) Name the two functional groups they all have;
…………………………….. …………………………………..
c) Deduce a general formula for α-amino acids using R for the alkyl/aryl group.
General Formula =
Notice, above, in Glycine the R group is H
In Phenylalanine it’s CH2C6H5
Student Activity 2
Use skeletal or displayed formula to show the structure of the following Amino Acids
Lysine, R group is (CH2)4NH2
Aspartic acid, R group is CH2COOH
Given these Amino Acids, give the R group using structural formula.
Isoleucine
Methionine
These are all α-amino acids; the amino and carboxyl groups are on the same carbon atom. Other types of amino acid have these two groups separated on the chain e.g.
Naming
Use systematic names for these two amino acids
Formation of zwitterions
The acidic carboxyl group and the basic amine group in an amino acid can react with each other to form an internal salt, known as a zwitterion. A zwitterion has no net charge as the positive and negative charges cancel each other out; it is a neutral ion. A proton is lost from the carboxylic acid and a dative bond is made between the proton and the lone pair of the nitrogen atom.
Zwitterions form at a particular pH value which is unique to each amino acid. This pH is called the isoelectric point: for glycine this is 6.06, for phenylalanine this is 5.48 and for proline this is 6.30. You will be given these pH values and do not need to remember them. It is actually the R group that determines the value of the isoelectric point. A carboxylic acid R group will lower the isoelectric point. . An amine R group will raise the isoelectric point. These zwitterions can play an important role in the buffering of blood – too much acid in the blood from excess carbon dioxide for example, leads to a coma. Buffers play an important role in biological systems.
Student activity 3
Match the amino acids to their isoelectric points.
pH 6.00 pH 9.59 pH 3.22
Reactions of amino acids
a)Acid and base properties
The amino acid has an acidic carboxyl group and a basic amine group. Treat each functional group as a separate reacting centre: the -COOH can be deprotonated and the -NH2 can be protonated. If other –OH groups are present (from secondary alcohols) then leave them unreacted.
b) Esterification and Other Reactions
Also, the carboxylic acid functional group can react with alcohols in the presence of sulphuric acid to produce an ester.
Student Activity 4
a) Draw the structure of phenylalanine at pH 2 (in acid solution)
phenylalanine
b) Draw the structure of proline at pH 12 (in alkaline solution)
proline
c) Draw the product formed when of proline is heated with aqueous methanol in the presence of sulphuric acid.
Proline
d) Draw the product when Glutamic acid reacts with sodium
Formation of the peptide bond
Amino acids link together with the elimination of a water molecule to form a peptide (or amide) linkage. This is called a condensation reaction because a small molecule (water in this case) is formed. When two amino acids join together a dipeptide is made.
Student Activity 5
a) Using your model of glycine, join with another student, make a dipeptide and lose a water molecule between you. Reverse the process to get back to your starting molecules (this reverse process is hydrolysis).
b) One of you should now replace a hydrogen atom on the central carbon atom for a methyl group (you have made a new amino acid called alanine) and repeat the condensation. Compare your new dipeptide with one from the next table. Will it be the same?
Polypeptides and proteins
A protein is a chain of 40 or more amino acids linked together by peptide linkages. Proteins and polypeptides are formed by many condensation polymerisations involving the loss of water. Each time an additional amino acid is added to the chain, a molecule of water is formed. A polypeptide is a peptide containing more than 3 amino acid molecules (monomers).
Student Activity 6 Complete the equations below to show the condensations between two amino acids.
a)
alanine glycine
b)
c)
d) Draw all three amino acids and a tripeptide produced in the order glycine, phenylalanine and proline
e) How many different tripeptides could you make from these three amino acids (Ala, Gly and Phe)?
Note: use of a GC and a spectral database to identify tripeptides from a mixture
Formation of Dimers (Cyclic Peptides)
When strongly heated two alpha amino acids condense together to form a cyclic dimer
They all have structures as shown below. In this case this if R1=R2=H
The two amino acids that reacted together must be glycine
Student Activity 7
a)Draw the structure Alanine ( R group is CH3)
Draw the structure of Valine ( R group is CH(CH3)2)
Now draw the cylcic dimer that forms when these two amino acids condense under strong heating.
b) Draw the two amino acids used to form this dimer.
Hydrolysis
This term means the splitting of water by reaction with another compound. It means the other compound also gets split.
If you split a protein you produce amino acids.
The hydrolysis of a protein requires 6 moldm-3 HCl, refluxed for 24 hours. The products are amino acids. This process can also be carried out in the laboratory by heating the protein with aqueous alkali. In the natural world the same reaction occurs rapidly using a suitable enzyme such as trypsin. This catalysis allows for far less energy, therefore the reaction can occur at lower temperature.
Acid Hydrolysis can be shown using the equation below.
Notice that we get the protonated form of the amino group here.
Base Hydrolysis can be shown using the equation below.
Here we get the carboxylate salt form of the carboxyl group here.
Student activity 8
a) Show the products of base hydrolysis of the dipeptide shown.
(You can always redraw the molecule below first, in the skeletal formula is this make it look less busy!)
b) Show the products of acid hydrolysis of the dipeptide shown.
Optical Isomerism
You have already learned about E/Z isomerism; this is a type of stereoisomerism. These are compounds with the same molecular formula and structural formula but a different spatial arrangement of their atoms. Here we meet another kind of stereoisomerism called optical Isomerism.
It was first discovered by Louis Pasteur who looked at crystals of lactic acid under a microscope and found there were two types.
Lactic acid has the systematic name 2-hydroxypropanoic acid.
Student Activity 9
a) Draw the structural formula of lactic acid
b) Make a model of lactic acid. Compare your model with the one on the next table.
c) Look at the middle carbon atom, how many different groups/atoms has it got around it?
d) Make the two different lactic acid molecules that are mirror images of each other? They should be non-super imposable (like left and right hand gloves)
e) Draw a 3D diagram using two solid lines, a wedge and a dotted line. Start with the chiral carbon and show a tetrahedral arrangement.
Optical isomers exist when there is a chiral (Greek for handedness) carbon atom; one with four different groups/atoms attached to it: the carbon atom is said to be asymmetrically substituted. Two different forms of the molecule are possible. They are called enantiomers, some books call them + and -, others L, D and yet others L and R. The only practical way to tell the difference between them is that they rotate the plane of polarised light in opposite directions. A machine called a polarimeter does this. If you had a 50:50 mixture of the two isomers in the machine you would see no rotation. This is called a racemic mixture or a racemate. An individual naturally occurring protein is made from amino acids of only one optical isomer. Each natural process only produces one of the two optical isomers, because enzymes are stereospecific.
Student Activity 10
1) Draw the two optical isomers of alanine (2-aminopropanoic acid) as mirror images.
2) Look at these molecules. Is there a chiral carbon? Asterisk it if you find one.
a) CH3CH2CHBrCH2CH3
b) CH3CH2CHBrCH3
c)
d) butan-2-ol
e)
Which other form of stereoisomerism is present here? Circle the substructure which allows this.
f)
g)
Is this an α-amino acid?
Chiral drugs
As you may have found through your research, a drug which has a chiral centre presents various difficulties. One isomer may be pharmacologically inactive, whilst the other produces the desired effect. One isomer may produce serious side effects which seriously affect the health of the patient.
Salbutamol is used to treat asthma. Drugs such as salbutamol contain a chiral centre.
They can be made in an optically active form (a single active enantiomer) by:
· Using a chiral catalyst (a chiral transition metal catalyst);
· Using chiral pool synthesis (taking an existing chiral compound and performing a synthesis which does not change the symmetry);
· Using enzymes to produce a chiral centre.
Also, the racemic mixture can be separated by chiral resolution; this involves using a chiral stationary phase when performing chromatography.
Diastereoisomers
These are compounds with two chiral centres.
Student activity 11
1. Draw the other three structures which represent different isomers.
2. Identify the different forms of isomerism present.
Student Activity 12
OCR Jun11
This is what you should know!
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