1. 2-Amino Acids & Zwitterions
Naturally occurring amino acids are 2-amino acids (alpha-amino acids) with the general formula R-CH(NH₂)-COOH. With the exception of glycine (where R = H), all natural 2-amino acids have four different groups attached to the central alpha carbon and are therefore chiral.
H₂N-CH(R)-COOH ⇌ ⁺H₃N-CH(R)-COO⁻ This dipolar ion containing both a positive and a negative formal charge is called a zwitterion.
Glycine in three forms
Glycine is the simplest amino acid (R = H).
- Zwitterion: H₃N⁺CH₂COO⁻
- In acid: H₃N⁺CH₂COOH (the COO⁻ gains H⁺)
- In alkali: H₂NCH₂COO⁻ (the NH₃⁺ loses H⁺)
Why Amino Acids Have Exceptionally High Melting Points
Amino acids are crystalline solids with melting points typically above 200 °C. This is because they exist as zwitterions that assemble into a giant ionic lattice held together by strong electrostatic ionic attractions between oppositely charged -NH₃⁺ and -COO⁻ groups, requiring vast thermal energy to disrupt.
2. Amino Acids in Acidic and Alkaline Solution
Beyond the OxfordAQA specification
Isoelectric point (pI): the pH at which an amino acid exists mainly as a zwitterion with a net charge of zero. 9620 does not require the isoelectric point or electrophoresis.
Behaviour When pH is Altered
- In Strongly Acidic Solution (excess H⁺):
The basic -COO⁻ group accepts a proton to become -COOH:
⁺H₃N-CH(R)-COO⁻ + H⁺ ⇌ ⁺H₃N-CH(R)-COOH
The molecule carries a net positive charge (+1). Beyond the OxfordAQA specification: in gel electrophoresis it moves towards the negative electrode. - In Strongly Alkaline Solution (excess OH⁻):
The acidic -NH₃⁺ group loses a proton to hydroxide ions:
⁺H₃N-CH(R)-COO⁻ + OH⁻ ⇌ H₂N-CH(R)-COO⁻ + H₂O
The molecule carries a net negative charge (-1). Beyond the OxfordAQA specification: in gel electrophoresis it moves towards the positive electrode.
3. Zwitterion Equilibrium Diagram
Beyond the OxfordAQA specification: the isoelectric point and electrophoresis labels in this diagram are not required.
4. Protein Structure Levels
Proteins are biopolymers constructed from amino acids linked together by peptide bonds (-CONH-).
Peptide links and dipeptides
The COOH group of one amino acid reacts with the NH₂ group of another. Water is lost and a peptide (amide) link, -CONH-, forms. Two amino acids give a dipeptide.
Glycine and alanine can join in two ways, so they give two different dipeptides:
A tripeptide has three amino acids and two peptide links. For example, Gly-Ala-Gly is:
H₂NCH₂CONHCH(CH₃)CONHCH₂COOH
Hydrolysis of peptides and proteins
Heat with hot 6 mol dm⁻³ HCl. The peptide links are hydrolysed and the amino acids are released. In the acid, the amino acids are protonated, for example glycine is present as H₃N⁺CH₂COOH.
The amino acids can then be separated and identified by thin-layer chromatography. See Chromatography: amino acids by TLC.
Levels of protein structure
| Structural Level | Description | Types of Bonds Responsible |
|---|---|---|
| Primary (1°) | The specific linear sequence of amino acids in the polypeptide chain. | Strong covalent peptide bonds (-CONH-). (Hydrolysed by heating with hot 6 mol dm⁻³ HCl.) |
| Secondary (2°) | Local regular folding of the polypeptide chain into alpha-helices or beta-pleated sheets. | Hydrogen bonding between C=O of one peptide link and N-H of another peptide link along the backbone. |
| Tertiary (3°) | The overall 3-dimensional folding of the entire polypeptide chain into its active globular or fibrous shape. | Four R-group interactions:
1. Disulfide bridges: Covalent -S-S- bonds between cysteine residues. 2. Ionic salt bridges: Between -COO⁻ and -NH₃⁺ groups. 3. Hydrogen bonds: Between polar R-groups (-OH, -NH₂). 4. van der Waals dispersion forces: Between non-polar hydrocarbon R-groups. |
Identify each level from a diagram: a chain of labelled amino acids shows the primary structure. A coil (α-helix) or flat zigzag strands joined by hydrogen bonds (β-pleated sheet) show the secondary structure. A whole chain folded into a 3D shape, with links such as S-S bonds, shows the tertiary structure.
5. Enzymes & Active Site Stereospecificity
Beyond the OxfordAQA specification
Enzymes are globular proteins that act as biological catalysts. The reactant molecule (substrate) binds to a specific region called the active site.
Stereospecificity of Enzyme Active Sites
Because proteins are constructed exclusively from chiral L-amino acids, the 3D active site itself is a chiral cavity. Consequently, enzymes display absolute stereospecificity: only ONE enantiomer of a chiral substrate can fit into the active site with its functional groups aligned to form intermolecular bonds (lock-and-key model). The mirror-image enantiomer cannot bind properly and remains unreacted.
6. Cisplatin and DNA
Beyond the OxfordAQA specification
9620 does not require the structure of DNA or base pairing. This background helps explain how cisplatin works.
Deoxyribonucleic acid (DNA) is a macromolecule that encodes genetic information. A single DNA strand is a polymer of nucleotides, each consisting of:
1. A phosphate group
2. A 2-deoxyribose sugar molecule
3. A nitrogenous base (Adenine, Thymine, Cytosine, or Guanine)
Complementary Base Pairing in the Double Helix
DNA consists of two antiparallel polynucleotide strands held together in a double helix by hydrogen bonds between complementary base pairs:
- Adenine (A) pairs with Thymine (T) via TWO hydrogen bonds.
- Guanine (G) pairs with Cytosine (C) via THREE hydrogen bonds.
Action of the Anticancer Drug Cisplatin
Cisplatin, [Pt(NH₃)₂Cl₂], is a square planar platinum(II) complex used in cancer chemotherapy:
- Inside the cell, one Cl⁻ ligand is replaced by a water molecule.
- The platinum then bonds to a nitrogen atom on a guanine base in DNA.
- Usually two bonds form to the DNA. This distorts the DNA, so it cannot replicate.
- The cancer cells cannot divide.
Note: the 9620 specification text says cisplatin binds to "a nitrogen atom on a protein". The target is a nitrogen atom on a guanine base in DNA, so learn the DNA version, and note the spec wording.
Adverse Effects and Risks
- Cisplatin also attacks healthy cells that divide quickly. This causes hair loss, nausea and kidney damage.
- The risks are reduced by using low doses and by targeting the tumour.
- Society must balance the benefits of the drug against its side effects.
7. Worked Examples
(a) As a solid at room temperature.
(b) In aqueous solution at pH 1.
(c) In aqueous solution at pH 13.
Solution:
- (a) Solid at room temperature: Exists as a zwitterion:
CH₃-CH(NH₃⁺)-COO⁻ - (b) At pH 1 (strongly acidic): Carboxyl group is protonated:
CH₃-CH(NH₃⁺)-COOH (cation, net charge +1) - (c) At pH 13 (strongly alkaline): Amino group loses a proton:
CH₃-CH(NH₂)-COO⁻ (anion, net charge -1)
Beyond the OxfordAQA specification
Calculate the total number of hydrogen bonds holding the two strands together in this segment.
Calculation:
Each A-T base pair is held by 2 hydrogen bonds: 15 × 2 = 30 hydrogen bonds.
Each G-C base pair is held by 3 hydrogen bonds: 25 × 3 = 75 hydrogen bonds.
Total hydrogen bonds = 30 + 75 = 105 hydrogen bonds.
Go deeper
These UK AQA pages cover the same ideas in more detail. They may include content that is not in 9620.
8. Practice Questions
Show Answer & Mark Scheme
Answer:
- (a) H₃N⁺CH₂COOH (1)
- (b) H₂NCH₂COO⁻ (1)
Show Answer & Mark Scheme
Answer:
- H₂NCH₂CONHCH(CH₃)COOH (1)
- H₂NCH(CH₃)CONHCH₂COOH (1)
Show Answer & Mark Scheme
Answer: hydrogen bonds (1); ionic attractions (1); disulfide (S-S) bonds between cysteine residues (1).
Show Answer & Mark Scheme
Answer:
- A Cl⁻ ligand is replaced by water (1).
- The Pt bonds to a nitrogen atom on a guanine base in DNA (1).
- This distorts the DNA so it cannot replicate, so the cell cannot divide (1).
Show Answer & Mark Scheme
Answer:
- Hair loss, nausea or kidney damage (it also attacks healthy cells that divide quickly) (1).
- Use low doses, or target the tumour (1).