Welcome to Amino Acids (CCEA A2 Chemistry)
Welcome to one of the most fascinating topics in your A2 2 Organic Nitrogen Chemistry module! Amino acids are the fundamental building blocks of life, forming every protein, enzyme, and peptide in living organisms. In this chapter, we will demystify their structures, uncover their unique dual acid-base personality, explore how they link together, and learn how chemists separate and identify them.
Don't worry if this seems a bit tricky at first! By breaking down each concept into bite-sized steps, you will quickly master every reaction, structure, and exam question that CCEA can throw your way.
---1. What is an \(\alpha\)-Amino Acid? Structure & Nomenclature
The Core Structure
An \(\alpha\)-amino acid (systematically known as a 2-amino carboxylic acid) is an organic molecule that contains two essential functional groups attached to the very same carbon atom:
• A basic amino group (\(-\text{NH}_2\))
• An acidic carboxylic acid group (\(-\text{COOH}\))
• A hydrogen atom (\(-\text{H}\))
• A variable side-chain known as the \(\text{R}\) group
Because both key groups are bonded to carbon-2 (the \(\alpha\)-carbon right next to the carboxylic acid carbon), its general structural formula is written as \(\text{R–CH}(\text{NH}_2)\text{COOH}\) or \(\text{H}_2\text{N–CHR–COOH}\).
Systematic IUPAC Naming
When naming amino acids systematically, always treat the carboxylic acid carbon as carbon-1 (\(\text{C}1\)). The carbon carrying the amino group is carbon-2 (\(\text{C}2\)):
• Glycine (\(\text{R} = -\text{H}\)): \(\text{H}_2\text{N–CH}_2\text{–COOH}\) is systematically named 2-aminoethanoic acid (or aminoethanoic acid).
• Alanine (\(\text{R} = -\text{CH}_3\)): \(\text{CH}_3\text{–CH}(\text{NH}_2)\text{–COOH}\) is systematically named 2-aminopropanoic acid.
Key Takeaway: All standard \(\alpha\)-amino acids have the \(-\text{NH}_2\) and \(-\text{COOH}\) groups on carbon-2, giving them the general formula \(\text{R–CH}(\text{NH}_2)\text{COOH}\).
---2. Chirality and Optical Activity
The Chiral Centre
Recall from your stereochemistry studies that an asymmetric or chiral carbon centre is a carbon atom bonded to four completely different atoms or groups of atoms.
In all naturally occurring \(\alpha\)-amino acids (except glycine), the \(\alpha\)-carbon is attached to four distinct groups:
1. The amino group (\(-\text{NH}_2\))
2. The carboxylic acid group (\(-\text{COOH}\))
3. A hydrogen atom (\(-\text{H}\))
4. The specific side chain (\(-\text{R}\))
Optical Isomerism
Because they possess a chiral centre, these amino acids are optically active. They exist as a pair of non-superimposable mirror-image forms called enantiomers that rotate the plane of plane-polarised light in equal and opposite directions.
The Crucial Exception: Glycine
Examiner Alert: Glycine (\(\text{H}_2\text{N–CH}_2\text{–COOH}\)) is the only standard \(\alpha\)-amino acid that is optically inactive (achiral). Why? Its \(\text{R}\) group is simply a hydrogen atom (\(-\text{H}\)). This means its \(\alpha\)-carbon is bonded to two identical hydrogen atoms, so it does not have four different groups.
Key Takeaway: All naturally occurring \(\alpha\)-amino acids are chiral and optically active except glycine, which has two hydrogen atoms on carbon-2.
---3. Zwitterions and Physical Properties
What is a Zwitterion?
Amino acids do not actually exist as neutral, uncharged \(\text{H}_2\text{N–CHR–COOH}\) molecules in the solid state or in neutral aqueous solution. Instead, an internal acid-base proton transfer takes place:
• The acidic carboxylic acid group (\(-\text{COOH}\)) loses a proton (\(\text{H}^+\)) to form a negatively charged carboxylate group (\(-\text{COO}^-\)).
• The basic amino group (\(-\text{NH}_2\)) accepts that proton to form a positively charged ammonium ion (\(-\text{NH}_3^+\)).
The resulting dipolar species is called a zwitterion (from the German word for hybrid):
\(\text{R–CH}(\text{NH}_3^+)\text{COO}^-\)
A zwitterion carries both a permanent positive charge and a permanent negative charge on different parts of the same molecule, making it electrically neutral overall.
Why Do Amino Acids Have High Melting Points?
Unlike standard organic molecules of similar size (which are held together by relatively weak London dispersion forces or simple hydrogen bonds), solid amino acids exist in an ionic lattice held together by strong electrostatic attractions between oppositely charged zwitterions.
As a result, amino acids:
• Are white, crystalline solids.
• Have unusually high melting points (often decomposing before they melt) because a large amount of energy is required to break these strong ionic attractions.
Solubility
• In Water: Highly soluble. The charged \(\text{NH}_3^+\) and \(\text{COO}^-\) groups form strong ion-dipole attractions with polar water molecules (favourable hydration).
• In Non-polar Organic Solvents: Virtually insoluble (e.g., in hexane or benzene), because non-polar solvents cannot overcome the strong ionic electrostatic forces holding the zwitterions together.
Key Takeaway: The internal transfer of a proton creates a dipolar zwitterion \(\text{R–CH}(\text{NH}_3^+)\text{COO}^-\), leading to ionic lattice behaviour, high melting points, and water solubility.
---4. Amphoteric Nature & The Effect of pH
Amphoteric Behaviour
Because amino acids contain both acidic (\(-\text{NH}_3^+\) / \(-\text{COOH}\)) and basic (\(-\text{COO}^-\) / \(-\text{NH}_2\)) groups, they are amphoteric — they can react with and neutralise both acids and bases.
The Isoelectric Point (\(\text{pI}\))
The isoelectric point (\(\text{pI}\)) is the specific \(\text{pH}\) at which an amino acid exists predominantly in its dipolar zwitterionic form with no net overall electrical charge.
What Happens When You Change the pH?
1. In Strongly Acidic Solutions (Low \(\text{pH}\) / Excess \(\text{H}^+\)):
When acid is added, the carboxylate group (\(-\text{COO}^-\)) acts as a base and accepts a proton (\(\text{H}^+\)) to reform the neutral \(-\text{COOH}\) group. The amino acid becomes a cation (net positive charge):
\(\text{R–CH}(\text{NH}_3^+)\text{COO}^- + \text{H}^+ \rightleftharpoons \text{R–CH}(\text{NH}_3^+)\text{COOH}\)
Net charge: \(+1\)
2. In Strongly Alkaline Solutions (High \(\text{pH}\) / Excess \(\text{OH}^-\)):
When alkali is added, the ammonium group (\(-\text{NH}_3^+\)) acts as an acid and donates a proton to the hydroxide ion (\(\text{OH}^-\)), reverting to a neutral \(-\text{NH}_2\) group and forming water. The amino acid becomes an anion (net negative charge):
\(\text{R–CH}(\text{NH}_3^+)\text{COO}^- + \text{OH}^- \rightleftharpoons \text{R–CH}(\text{NH}_2)\text{COO}^- + \text{H}_2\text{O}\)
Net charge: \(-1\)
Quick Summary Table
• Low \(\text{pH}\) (Acidic): Structure is \(\text{R–CH}(\text{NH}_3^+)\text{COOH}\) \(\rightarrow\) Cation (Positive charge)
• Isoelectric Point (\(\text{pH} = \text{pI}\)): Structure is \(\text{R–CH}(\text{NH}_3^+)\text{COO}^-\) \(\rightarrow\) Zwitterion (Neutral, net zero charge)
• High \(\text{pH}\) (Alkaline): Structure is \(\text{R–CH}(\text{NH}_2)\text{COO}^-\) \(\rightarrow\) Anion (Negative charge)
Memory Trick: "Add acid \(\rightarrow\) Add \(\text{H}^+\) (creates positive ion). Add alkali \(\rightarrow\) Remove \(\text{H}^+\) (leaves negative ion)."
---5. Peptide Bonds, Dipeptides & Hydrolysis
Condensation Reactions and the Peptide Link
Two amino acids can join together in a condensation reaction. The carboxylic acid group (\(-\text{COOH}\)) of one amino acid reacts with the amino group (\(-\text{NH}_2\)) of another, eliminating a small molecule of water (\(\text{H}_2\text{O}\)).
This links the two units together via a peptide link (also called a secondary amide link):
\(-\text{CO–NH}-\) or \(-\text{C}(=\text{O})-\text{NH}-\)
Dipeptide Formation & Isomerism
A dipeptide is a molecule made of exactly two amino acid units joined by one peptide link. When two different amino acids react (for instance, Glycine and Alanine), two different constitutional dipeptide isomers can be formed depending on which molecule provides the \(-\text{COOH}\) group and which provides the \(-\text{NH}_2\) group:
1. Glycylalanine (Gly-Ala): Glycine donates the \(-\text{COOH}\) group and Alanine donates the \(-\text{NH}_2\) group:
\(\text{H}_2\text{N–CH}_2\text{–CO–NH–CH}(\text{CH}_3)\text{–COOH}\)
2. Alanylglycine (Ala-Gly): Alanine donates the \(-\text{COOH}\) group and Glycine donates the \(-\text{NH}_2\) group:
\(\text{H}_2\text{N–CH}(\text{CH}_3)\text{–CO–NH–CH}_2\text{–COOH}\)
Hydrolysis of Peptides
The peptide bond can be broken back down into its constituent amino acids by hydrolysis (splitting a bond using water). In the laboratory, this is typically performed by:
• Heating under reflux with concentrated acid (such as \(6\text{ mol dm}^{-3}\ \text{HCl}\)) or aqueous alkali.
Key Takeaway: Condensation forms a peptide link (\(-\text{CO–NH}-\)) with the loss of \(\text{H}_2\text{O}\). Hydrolysis (reflux with \(6\text{ mol dm}^{-3}\ \text{HCl}\)) breaks the link back into free amino acids.
---6. Separation and Identification of Amino Acids
1. Chromatography (TLC and Paper Chromatography)
A protein hydrolysate (mixture of amino acids) can be separated and identified using thin-layer chromatography (TLC) or paper chromatography:
• Spotting & Running: A small spot of the amino acid mixture is placed on the baseline of the plate/paper and placed into a suitable solvent tank.
• Locating Agent (Ninhydrin): Because amino acids are colourless, the dried plate is sprayed with ninhydrin and gently heated. Ninhydrin reacts with amino acids to produce distinct purple/blue spots.
• Identification via \(R_f\) Values: The retardation factor (\(R_f\)) is calculated for each spot:
\(R_f = \frac{\text{distance moved by amino acid}}{\text{distance moved by solvent front}}\)
By comparing the experimental \(R_f\) values with tables of known standard values under the same solvent conditions, each amino acid can be identified.
2. Electrophoresis
Electrophoresis separates amino acids based on their net electrical charge, molecular size, and mass at a carefully controlled buffer \(\text{pH}\):
• A sample is placed on a supporting strip (paper or gel) wetted with a buffer solution, and a direct electric potential difference (voltage) is applied.
• Cations (positively charged amino acids, where buffer \(\text{pH} < \text{pI}\)) migrate towards the negatively charged cathode.
• Anions (negatively charged amino acids, where buffer \(\text{pH} > \text{pI}\)) migrate towards the positively charged anode.
• Amino acids at their isoelectric point (\(\text{pH} = \text{pI}\)) have no net charge and do not migrate.
Key Takeaway: Amino acids are visualised on chromatograms using purple-staining ninhydrin. In electrophoresis, migration depends on charge at the buffer \(\text{pH}\) (cations to cathode, anions to anode).
---7. Common Exam Pitfalls & Examiner Tips
1. Drawing Zwitterion Charges on the Wrong Atoms:
Always ensure the positive charge is clearly on the nitrogen atom (\(-\text{NH}_3^+\)) and the negative charge is on the oxygen atom (\(-\text{COO}^-\)). Never write \(\text{H}_3\text{N–}\) with a missing plus sign or put a negative charge on a carbon atom.
2. Claiming "All" Amino Acids are Optically Active:
Remember: Glycine is achiral. Stating that all amino acids show optical isomerism will lose you easy marks. Always specify "all naturally occurring \(\alpha\)-amino acids except glycine".
3. Inverting Acid/Base Behaviour:
Students often wrongly protonate the amino group in alkali or deprotonate the acid group in acid! Remember:
• Acid added (\(\text{low pH}\)) \(\rightarrow\) \(\text{COO}^-\) becomes \(-\text{COOH}\) (net charge \(+1\)).
• Alkali added (\(\text{high pH}\)) \(\rightarrow\) \(\text{NH}_3^+\) becomes \(-\text{NH}_2\) (net charge \(-1\)).
4. Drawing Peptide Link Connectivity:
When drawing a peptide bond, clearly show the carbonyl double bond: \(-\text{C}(=\text{O})-\text{NH}-\). Don't accidentally omit the oxygen atom or draw a simple single-bonded amine link \(-\text{CH}_2-\text{NH}-\).
5. Forgetting Dipeptide Isomers:
When asked how many dipeptides form from two different amino acids \(\text{A}\) and \(\text{B}\), remember that \(\text{A-B}\) and \(\text{B-A}\) are completely different structural isomers!
Chapter Quick Review
• General Formula: \(\text{R–CH}(\text{NH}_2)\text{COOH}\) (2-amino carboxylic acids).
• Chirality: Carbon-2 is chiral in all \(\alpha\)-amino acids except glycine (\(\text{R} = -\text{H}\)).
• Zwitterion: \(\text{R–CH}(\text{NH}_3^+)\text{COO}^-\) (dipolar, neutral overall). Gives high melting points and water solubility via ionic lattice forces.
• Acid Conditions (\(\text{low pH}\)): Forms cation \(\text{R–CH}(\text{NH}_3^+)\text{COOH}\).
• Alkaline Conditions (\(\text{high pH}\)): Forms anion \(\text{R–CH}(\text{NH}_2)\text{COO}^-\).
• Peptide Bond: Formed by condensation (\(-\text{CO–NH}-\) with loss of \(\text{H}_2\text{O}\)); broken by acid/alkaline hydrolysis (\(6\text{ mol dm}^{-3}\ \text{HCl}\)).
• Separation: Chromatography (ninhydrin spray turns spots purple) & Electrophoresis (movement governed by net charge at buffer \(\text{pH}\)).