Whiteboard Chemistry with Joe White

Amino Acids, Proteins & DNA

The molecules of life through a chemist’s eyes: amino acids as zwitterions, the peptide bond that builds proteins, the bonding that holds them in shape, DNA base pairing, and how cisplatin stops a cancer cell dividing.

AQA 7404/7405 Paper 2 A-level only
Hero motif · to come From zwitterion to double helix
The big idea

Three families, one thread: amino acids carry both an acid and a base group, so they behave unusually; join them by peptide bonds and you get proteins (including enzymes); and DNA stores information through hydrogen-bonded base pairs. The chemistry you already know — acids and bases, condensation, hydrogen bonding, ligand substitution — explains all of it.

Amino acids — zwitterions & acid/base behaviour

An α-amino acid has an amine group and a carboxylic acid group on the same carbon: H2N–CHR–COOH, where R varies. Because it carries both an acid and a base, an amino acid behaves as both.

The zwitterion and its ions
  • Around neutral pH the acid group donates its H+ to the amine group on the same molecule, giving a zwitterion: +H3N–CHR–COO (overall neutral, but with both a + and a − charge).
  • In acid solution the –COO is protonated → a cation: +H3N–CHR–COOH.
  • In alkaline solution the –NH3+ loses H+ → an anion: H2N–CHR–COO.
Figure F1 · illustration to come Cation ↔ zwitterion ↔ anion Add H+ in acid; remove H+ in alkali.
Almost every amino acid also has a chiral centre (the α-carbon) — glycine, where R = H, is the exception.
🧪 Exam-style questions
Q1 [1 mark]

Which is the structure of the zwitterion of the amino acid alanine, CH3CH(NH2)COOH?

  1. CH3CH(NH2)COOH
  2. CH3CH(NH3+)COOH
  3. CH3CH(NH2)COO
  4. CH3CH(NH3+)COO
A zwitterion has both a protonated amine (–NH3+) and a deprotonated acid (–COO) — overall neutral, one + and one −.
Q2 [1 mark]

Which is the main species present in a solution of the amino acid at pH = 14?

  1. +H3N–CHR–COOH
  2. +H3N–CHR–COO
  3. H2N–CHR–COOH
  4. H2N–CHR–COO
At high pH (excess OH) both acidic protons are removed: the amine is neutral (–NH2) and the acid is deprotonated (–COO), so the species is an anion.

Source: AQA A-Level Chemistry past papers.

Proteins — peptides & structure

Amino acids join by peptide bonds: the –COOH of one reacts with the –NH2 of the next, forming an amide link (–CO–NH–) and releasing water — a condensation reaction. A chain of them is a protein. Heating with hot aqueous acid (or alkali) hydrolyses the peptide bonds back to the constituent amino acids.

Three levels of structure
  • Primary — the sequence of amino acids in the chain.
  • Secondary — the chain coils into an α-helix or folds into a β-pleated sheet, held by hydrogen bonds between the C=O and N–H of the backbone.
  • Tertiary — the overall 3-D shape, held by interactions between the R groups: hydrogen bonds, S–S disulfide bridges (between two cysteines), and ionic interactions.
Figure F2 · illustration to come Peptide bond & the three structure levels Backbone H-bonds shape the secondary; R-group interactions shape the tertiary.
The strongest R-group interaction is the disulfide bridge (covalent); hydrogen bonds and ionic interactions are weaker.

A mixture of amino acids from a hydrolysed protein can be separated and identified by thin-layer chromatography: colourless amino acids are located with ninhydrin or UV light and identified by their Rf values (see chromatography).

🧪 Exam-style questions
Q3 [1 mark]

Which interaction is mainly responsible for holding a protein’s secondary structure in an α-helix?

  1. covalent bonds
  2. hydrogen bonds
  3. ionic interactions
  4. van der Waals forces
The α-helix and β-pleated sheet are held by hydrogen bonds between the backbone C=O and N–H groups.
Q4 [4 marks]

In a protein, explain why the interaction between two cysteine R groups differs in strength from the interaction between a serine R group (–CH2OH) and an aspartic acid R group (–CH2COOH).

Show answer

Two cysteine R groups (each –CH2SH) form a disulfide (S–S) bridge. 1 mark

The serine and aspartic acid R groups form a hydrogen bond (between –OH and –COOH). 1 mark

The disulfide bridge is stronger than the hydrogen bond… 1 mark

…because a disulfide bridge is a covalent bond, whereas a hydrogen bond is not. 1 mark

Source: AQA A-Level Chemistry past papers.

Enzymes, DNA & cisplatin

Enzymes

Enzymes are proteins that act as catalysts. Each has a stereospecific active site whose shape is complementary to one substrate. Because the active site has a definite 3-D shape, only one enantiomer of a chiral substrate fits — the mirror image cannot bind, just as a left hand won’t fit a right glove. A drug can act as an inhibitor by binding to the active site and blocking it; computers are used to design molecules with the right complementary shape.

DNA

A nucleotide is a phosphate ion bonded to 2-deoxyribose (a pentose sugar), which is bonded to one of four bases (adenine, cytosine, guanine, thymine). Nucleotides link through covalent bonds between the phosphate of one and the sugar of the next, giving a sugar–phosphate backbone with the bases hanging off it. Two strands run alongside each other, held together by hydrogen bonds between complementary base pairs, twisted into a double helix.

Base pairing

Adenine pairs with thymine (two hydrogen bonds); cytosine pairs with guanine (three hydrogen bonds). The pairing is fixed by where the H-bond donors and acceptors sit on each base, which is why the two strands are complementary.

Cisplatin

Cisplatin, [Pt(NH3)2Cl2], is a Pt(II) anticancer drug. It stops a cancer cell dividing by preventing DNA replication: in a ligand replacement reaction, its chloride ligands are replaced as bonds form between the platinum and nitrogen atoms on guanine bases, cross-linking the DNA so the strands cannot separate. Because it also affects healthy dividing cells, it has adverse side effects — so society weighs the benefits against the harms.

Figure F3 · illustration to come Base pairing & the cisplatin cross-link A–T two H-bonds; C–G three; Pt bonds to N on guanine.
Cisplatin is the same ligand substitution chemistry you met with transition metals.
🧪 Exam-style questions
Q5 [1 mark]

When cisplatin bonds to DNA, which ligand replacement occurs?

  1. replacement of one NH3 ligand
  2. replacement of two NH3 ligands
  3. replacement of one NH3 ligand and one Cl ligand
  4. replacement of two Cl ligands
The two chloride ligands are replaced as Pt bonds to nitrogen atoms on guanine; the ammonia ligands stay in place.
Q6 [1 mark]

Which statement about enzymes is not correct?

  1. The tertiary structure of an enzyme influences which molecules can bind to the active site.
  2. The action of enzymes can be inhibited by a molecule that binds to the active site.
  3. Enzymes work equally well on both optical isomers of a substrate.
  4. Computers can be used to design drugs to block active sites on enzymes.
The active site is stereospecific, so only one enantiomer fits — enzymes do not work equally on both, making this the incorrect statement.
Q7 [2 marks]

After cisplatin enters a cell, one chloride ligand is replaced by a water molecule. Give the equation for this reaction.

Show answer

[Pt(NH3)2Cl2] + H2O → [Pt(NH3)2Cl(H2O)]+ + Cl 2 marks

(One mark for the correct formula and + charge of the complex; one for balancing, with Cl released.)

Source: AQA A-Level Chemistry past papers.

Pulling it together

The whole topic reuses chemistry you already own: acid–base behaviour explains zwitterions; condensation and hydrolysis build and break proteins; hydrogen bonding shapes proteins and pairs DNA bases; optical isomerism explains why an enzyme picks one enantiomer; and ligand substitution explains cisplatin.

The marks that get dropped
  • Drawing a zwitterion without both charges, or giving the wrong ion for the stated pH.
  • Naming the wrong bonding for each protein level — secondary is backbone H-bonds; tertiary adds S–S bridges and ionic interactions.
  • Swapping the base pairs or their H-bond counts — A–T (2), C–G (3).
  • Saying cisplatin “damages” DNA vaguely — it prevents replication by a ligand replacement bonding Pt to N on guanine.

Examiner reports note that structure marks are lost to careless charges and bonds — a zwitterion missing a charge, a peptide link drawn without the N–H, base pairs with the wrong number of hydrogen bonds. Draw them deliberately.

Optional structure/bonding matcher loads here. The tables and callouts above are the static fallback.

🎯 Build the mark scheme — protein bonding & active sites

Explain how the secondary and tertiary structures of a protein are held together, and why an enzyme’s active site binds only one enantiomer. Award yourself a mark for each:

  • Secondary: hydrogen bonds between the backbone C=O and N–H groups.
  • Tertiary: disulfide (S–S) bridges, hydrogen bonds and ionic interactions between R groups.
  • The active site is stereospecific — a definite 3-D shape.
  • Only one enantiomer is complementary / fits; its mirror image cannot bind.
3.3.13 Amino acids, proteins & DNA — Quick-reference summary
  • Amino acids: H2N–CHR–COOH form zwitterions (+H3N–CHR–COO); cation in acid, anion in alkali.
  • Proteins: amino acids joined by peptide bonds (condensation, water lost). Primary = sequence; secondary = α-helix / β-pleated sheet held by hydrogen bonds; tertiary = folded shape held by H-bonds, S–S disulfide bridges and ionic interactions. Hydrolysis (hot HCl) → the amino acids.
  • Enzymes are proteins with a stereospecific active site — only one enantiomer of a substrate fits. Drugs can act as inhibitors by blocking the active site.
  • DNA: nucleotide = phosphate + 2-deoxyribose + base; a sugar–phosphate backbone; two strands held by hydrogen-bonded base pairs (A–T two H-bonds, C–G three) in a double helix.
  • Cisplatin [Pt(NH3)2Cl2] stops DNA replicating by a ligand replacement — the two Cl are replaced as Pt bonds to N atoms on guanine, cross-linking the strands.

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