Amino Acids: The Building Blocks of Life (Syllabus 34.4)
Welcome to one of the most exciting topics in organic chemistry! Amino acids are often called the building blocks of life because they link together to form proteins, which do almost everything in our bodies, from moving muscles to carrying oxygen.
This chapter combines what you’ve learned about carboxylic acids and amines. Because amino acids contain both these functional groups, they have fascinating and unique properties, especially regarding how they react to changes in pH. Don't worry if this seems tricky at first; we will break down the concept of the zwitterion step-by-step!
1. Structure and Amphoteric Nature
1.1 The General Structure
Every amino acid shares a common core structure. They all contain two key functional groups attached to a central carbon atom, called the alpha-carbon (α-carbon):
- An Amino group (\(\text{NH}_2\)): A basic group.
- A Carboxyl group (\(\text{COOH}\)): An acidic group.
- A Hydrogen atom (\(\text{H}\)).
- A variable side chain (the R group). This R group determines the specific identity and properties of the amino acid (e.g., whether it is glycine, alanine, etc.).
The general formula looks like this: \(\text{H}_2\text{N} - \text{CHR} - \text{COOH}\)
1.2 Amphoteric Properties (Acting as both Acid and Base)
Because amino acids have both an acidic ($\text{COOH}$) group and a basic ($\text{NH}_2$) group, they are amphoteric (or amphiprotic).
Think of an amphoteric substance like a referee in a sports match—it can react differently depending on which "side" (acid or base) it is placed with.
Reaction in Acidic Conditions (Adding \(\text{H}^+\)):
The basic amino group (\(\text{NH}_2\)) accepts the proton (\(\text{H}^+\)) from the external acid, becoming positively charged.
$$ \text{H}_2\text{N} - \text{CHR} - \text{COOH} + \text{H}^+ \rightarrow \boldsymbol{^\oplus\text{H}_3\text{N} - \text{CHR} - \text{COOH}} $$
Net charge: Positive (\(+1\))
Reaction in Alkaline Conditions (Adding \(\text{OH}^-\)):
The acidic carboxyl group (\(\text{COOH}\)) donates a proton to the external alkali (\(\text{OH}^-\)), becoming negatively charged.
$$ \text{H}_2\text{N} - \text{CHR} - \text{COOH} + \text{OH}^- \rightarrow \boldsymbol{\text{H}_2\text{N} - \text{CHR} - \text{COO}^\ominus} + \text{H}_2\text{O} $$
Net charge: Negative (\(-1\))
Key Takeaway:
Amino acids are amphoteric because they contain both acidic (\(\text{COOH}\)) and basic (\(\text{NH}_2\)) groups. They can exist as positive ions in acid and negative ions in alkali.
2. The Zwitterion and the Isoelectric Point
In a neutral aqueous solution, amino acids undergo an internal acid-base reaction. This is one of the most important concepts for this topic!
2.1 Formation of the Zwitterion
In a neutral solution (or even in the solid state), the carboxyl group acts as an acid and gives its proton to the amino group, which acts as a base. This proton transfer happens within the same molecule.
The resulting species is called a zwitterion.
$$ \text{H}_2\text{N} - \text{CHR} - \text{COOH} \rightleftharpoons \boldsymbol{^\oplus\text{H}_3\text{N} - \text{CHR} - \text{COO}^\ominus} $$
- The carboxyl group is now the negatively charged carboxylate ion (\(\text{COO}^\ominus\)).
- The amino group is now the positively charged ammonium ion (\(^\oplus\text{NH}_3\)).
The zwitterion has two opposite charges within the same molecule, but the net charge is zero.
Did you know? "Zwitterion" comes from the German word "zwei," meaning two, referring to the two opposing charges.
2.2 The Isoelectric Point (\(\text{pI}\))
The isoelectric point (\(\text{pI}\)) is the specific pH value at which an amino acid exists predominantly in its zwitterion form, meaning the concentration of the positive ion and the negative ion are equal, resulting in zero overall net charge.
For most simple amino acids (where the R group is non-ionizable), the pI is close to neutral (around pH 6).
Importance of the Zwitterion and pI:
- Amino acids rarely exist as simple uncharged molecules (\(\text{H}_2\text{N} - \text{CHR} - \text{COOH}\)) in solution.
- The zwitterion structure explains why amino acids have much higher melting points than simple organic molecules of similar size (they exist as internal salts, held together by strong ionic attraction).
Quick Review Box:
| Condition | Dominant Form | Net Charge | | :---: | :---: | :---: | | Acidic (\(\text{pH} < \text{pI}\)) | Cation (\(^\oplus\text{NH}_3\text{COOH}\)) | +1 | | Neutral (\(\text{pH} = \text{pI}\)) | Zwitterion (\(^\oplus\text{NH}_3\text{COO}^\ominus\)) | 0 | | Alkaline (\(\text{pH} > \text{pI}\)) | Anion (\(\text{NH}_2\text{COO}^\ominus\)) | -1 |
3. Formation of Peptide Bonds (Condensation)
Amino acids link together to form polymers (proteins) through a special type of linkage called the peptide bond.
3.1 The Condensation Reaction
The peptide bond is formed by a condensation reaction between two amino acids:
- The carboxyl group (\(\text{COOH}\)) of one amino acid reacts with the amino group (\(\text{NH}_2\)) of a second amino acid.
- A molecule of water (\(\text{H}_2\text{O}\)) is eliminated.
- The resulting bond is an amide linkage, known specifically as a peptide bond.
$$ \text{R}^1\text{COOH} + \text{R}^2\text{NH}_2 \rightarrow \text{R}^1\text{CONHR}^2 + \text{H}_2\text{O} $$
The structure of the peptide bond is: \( - \text{CO} - \text{NH} - \)
3.2 Dipeptides and Tripeptides
- When two amino acids join, they form a dipeptide.
- When three amino acids join, they form a tripeptide.
Polymers consisting of many amino acids linked by peptide bonds are called polypeptides or proteins. Since the condensation reaction eliminates water, this is classified as a condensation polymerisation.
3.3 Hydrolysis
The peptide bond can be broken (hydrolysed) by heating the polypeptide with either concentrated acid or concentrated alkali. This is the reverse of condensation, where water is added back to break the amide linkage and regenerate the original amino acid components.
Key Takeaway:
Amino acids form amide (peptide) bonds via a condensation reaction, eliminating water to create di-, tri-, or polypeptides.
4. Electrophoresis: Separating Amino Acids
Electrophoresis is a technique used to separate mixtures of charged molecules (like amino acids and peptides) based on their movement in an electric field. The direction and speed of movement depend entirely on the molecule's net charge, which is controlled by the pH of the surrounding buffer solution.
4.1 The Principle
A mixture of amino acids is placed on a supporting medium (like paper or gel) soaked in a buffer solution. An electric field is applied. Particles move toward the electrode of the opposite charge.
Analogy: Imagine a crowd of people. Those carrying positive signs walk toward the negative gate, those carrying negative signs walk toward the positive gate, and those carrying balanced/neutral signs don't move much at all.
4.2 Interpreting Electrophoresis Results
To predict the direction of movement, you must compare the pH of the buffer solution to the isoelectric point (\(\text{pI}\)) of the amino acid.
- If \(\text{pH} < \text{pI}\) (Acidic Buffer):
In an acidic environment, there is a high concentration of \(\text{H}^+\). Both the amino and carboxyl groups will be protonated to some extent, but the overall molecule will have a net positive charge (\(^\oplus\text{H}_3\text{N} - \text{CHR} - \text{COOH}\)). The amino acid will migrate towards the Cathode (Negative Electrode).
- If \(\text{pH} > \text{pI}\) (Alkaline Buffer):
In an alkaline environment, \(\text{H}^+\) ions are removed. The carboxyl group is deprotonated, giving a net negative charge (\(\text{H}_2\text{N} - \text{CHR} - \text{COO}^\ominus\)). The amino acid will migrate towards the Anode (Positive Electrode).
- If \(\text{pH} = \text{pI}\) (Neutral Buffer for simple AA):
The amino acid exists predominantly as a zwitterion with a net zero charge. It will remain stationary (or close to the starting point) in the electric field.
4.3 Applying the concept to Dipeptides
Dipeptides (and tripeptides) also exhibit charge characteristics based on pH. Remember that when two amino acids join, the internal \(\text{CO}\) and \(\text{NH}\) groups are locked up in the peptide bond, but the groups at the ends remain functional:
- The N-terminus (the free \(\text{NH}_2\) end).
- The C-terminus (the free \(\text{COOH}\) end).
These two terminal groups determine the overall charge and movement, following the same rules as single amino acids:
- In acid, the N-terminus grabs \(\text{H}^+\), giving a positive charge (moves to cathode).
- In alkali, the C-terminus loses \(\text{H}^+\), giving a negative charge (moves to anode).
Note: The actual pI of a dipeptide is usually different from the pI of its constituent amino acids. You only need to be able to interpret and predict the direction of movement given the pH relative to the molecule's pI.
Key Takeaway:
Electrophoresis separates amino acids based on their net charge. If the pH is low (acidic), the amino acid is positive and moves to the cathode. If the pH is high (alkaline), the amino acid is negative and moves to the anode.