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Cisplatin forms coordinate bonds between platinum(II) and the N7 nitrogen of guanine bases, cross-linking DNA. Free AQA notes and 13 questions answered.
Cisplatin: How it Works is part of Amino acids, proteins and DNA (A-level only) in A Level AQA Chemistry.
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Cisplatin forms coordinate bonds between platinum(II) and the N7 nitrogen of guanine bases, cross-linking DNA. Free AQA notes and 13 questions answered.
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Use this lesson to stay inside Amino acids, proteins and DNA (A-level only) while connecting the detail back to the wider Organic chemistry topic.
Read the core explanations from Cisplatin: How it Works before testing yourself from memory.
Cancer cells divide uncontrollably. If you can stop a cancer cell from copying its DNA, you stop it from dividing — and that is precisely what cisplatin does.
Cisplatin is a platinum(II) coordination complex, and its anticancer activity comes directly from its ability to form a new bond with DNA. The chemistry you have already studied — coordinate bonding, ligand substitution, and transition metal complexes — is the exact toolkit needed to understand how this drug works at the molecular level.
This is one of the most elegant examples in A-level chemistry of how inorganic chemistry and biology intersect. By the end of this lesson, you will be able to explain the mechanism in precise exam language — which is exactly what AQA mark schemes reward.
Cisplatin has the formula cis-[Pt(NH3)2Cl2]. The central metal ion is platinum in the +2 oxidation state — Pt(II). Surrounding it are four ligands arranged in a square planar geometry: two ammonia molecules (NH3) and two chloride ions (Cl−).
Each ligand donates a lone pair of electrons to the Pt(II) centre, forming coordinate (dative covalent) bonds. The ammonia ligands donate through nitrogen; the chloride ligands donate through chlorine. This distinction matters enormously when the drug encounters DNA.
Inside the cell, the concentration of chloride ions is much lower than in the bloodstream. This shift in environment triggers the first stage of cisplatin's mechanism: the chloride ligands begin to be replaced by water molecules in a ligand replacement reaction.
Water molecules displace the chloride ligands one at a time, producing a positively charged aqua complex. This activated form of cisplatin is now highly reactive — it is primed to interact with DNA.
The aqua ligand is more easily displaced (more labile) from the platinum centre than chloride, making the aqua complex kinetically more reactive towards substitution by DNA bases. This increased lability is what makes the activated cisplatin so reactive towards DNA.
Here is where the mechanism becomes directly relevant to the AQA specification. Once cisplatin is activated, it undergoes a further ligand replacement reaction — this time with DNA itself.
DNA contains four bases: adenine, thymine, cytosine, and guanine. Guanine has a nitrogen atom at position 7 (N7) that carries a lone pair of electrons. This nitrogen acts as a ligand donor, displacing the water molecule from the activated cisplatin complex and forming a new coordinate bond between platinum and the N7 nitrogen of guanine.
The result is that cisplatin forms a cross-link between two guanine bases — typically on the same strand of DNA (an intrastrand cross-link). The platinum atom bridges the two guanines, physically distorting the DNA double helix.
For DNA to replicate, the two strands of the double helix must unwind and separate so that each strand can act as a template. Enzymes called DNA polymerases then read along each strand and build a complementary copy.
The platinum cross-link physically prevents this from happening. The Pt–N bonds lock two guanine bases together, creating a rigid kink in the DNA strand. The double helix cannot unwind properly at that site, and DNA polymerase cannot progress past the cross-link.
Without successful replication, the cancer cell cannot divide. The cell detects the DNA damage and, in many cases, triggers a programmed cell death pathway (apoptosis). This is why cisplatin is effective against rapidly dividing cancer cells — they are attempting to replicate their DNA far more frequently than normal cells.
It is worth stepping back and seeing the complete sequence as one connected chain of chemistry. Each stage follows logically from the last, and each stage involves concepts you have already studied in transition metal chemistry.
Worked example: Cisplatin's Mechanism: Step-by-Step
Trace the mechanism by which cisplatin prevents DNA replication, from its structure to its effect on the DNA double helix.
Answer: Cisplatin forms a bifunctional cross-link between two guanine N7 atoms via coordinate Pt–N bonds, physically blocking DNA replication and preventing cancer cell division.
AQA questions on cisplatin tend to use the command words explain or describe. The distinction matters: describe asks you to state what happens; explain requires you to give the chemical reason why it happens. Many students lose marks by describing the outcome without linking it to the underlying bonding chemistry.
When you write about the bond formed between cisplatin and DNA, you must specify: (1) it is a coordinate bond, (2) it forms between platinum and the nitrogen atom on guanine, and (3) this occurs via a ligand replacement reaction. All three elements are needed for full marks on an explain question.
Published by Revise Right. Use the official specification reference to check the requirements for your course. Content updated: 2026-09-05.
Move to the related lessons or back to the topic page when you need the wider sequence before exam-style practice.
Cisplatin, cis-[Pt(NH₃)₂Cl₂], is a square planar platinum(II) complex with two ammonia ligands and two chloride ligands, each bonded to platinum by a coordinate bond. The two chloride ligands are on the same side (cis); the trans isomer is pharmacologically inactive.
Cisplatin works by forming coordinate bonds between its platinum(II) centre and the N7 nitrogen atoms of guanine bases in DNA, cross-linking two guanines. The cross-link distorts the double helix so the strands cannot separate and DNA polymerase cannot pass, preventing DNA replication and cancer cell division.
Inside the cell, the chloride ion concentration is much lower than in the bloodstream, so water molecules replace the chloride ligands one at a time: cis-[Pt(NH₃)₂Cl₂] + H₂O → [Pt(NH₃)₂Cl(H₂O)]⁺ + Cl⁻. The aqua ligand is more easily displaced, so this activated complex is highly reactive towards DNA.
Cisplatin forms a coordinate bond between platinum and the N7 nitrogen atom of guanine, which donates its lone pair to Pt(II) in a ligand replacement reaction that displaces a water ligand. When two guanines are bonded, platinum forms an intrastrand cross-link.
Only the cis isomer of [Pt(NH₃)₂Cl₂] is active because its two chloride ligands are on the same side, so once they are replaced, platinum can bond to two neighbouring guanine bases and cross-link the DNA. The trans isomer cannot form the cross-link geometry needed to block DNA replication.
Guanine has a nitrogen atom at position 7, N7, that carries a lone pair of electrons. This nitrogen acts as a ligand donor, displacing the water molecule from activated cisplatin and forming a coordinate bond between platinum and N7.
The platinum cross-link locks two guanine bases together, creating a rigid kink in the DNA strand. The double helix cannot unwind properly at that site and DNA polymerase cannot progress past the cross-link, so the cancer cell cannot divide.
The platinum in cisplatin is in the +2 oxidation state, Pt(II). It sits at the centre of a square planar complex with two ammonia ligands and two chloride ligands, each donating a lone pair to form a coordinate bond.
An intrastrand cross-link forms when cisplatin bonds to two guanine bases on the same strand of DNA. The platinum atom bridges the two guanines through coordinate Pt–N bonds, physically distorting the DNA double helix.
Cancer cells divide uncontrollably and attempt to replicate their DNA far more frequently than normal cells. Cisplatin blocks DNA replication, so it is effective against rapidly dividing cancer cells, and the damage often triggers a programmed cell death pathway.
The aqua ligand is more easily displaced, or more labile, from the platinum centre than chloride. This makes the positively charged aqua complex kinetically more reactive towards substitution by DNA bases.
In the first step, [Pt(NH₃)₂Cl(H₂O)]⁺ reacts with guanine: the N7 nitrogen of guanine donates its lone pair to Pt(II), displacing the water ligand. A second guanine then displaces the remaining chloride, so the platinum bridges two guanine bases.
Cisplatin forms two coordinate bonds with DNA, one to the N7 nitrogen of each of two guanine bases. The first displaces a water ligand and the second displaces the remaining chloride, giving a bifunctional cross-link that bridges the two guanines.