Chemguide: Support for CIE A level Chemistry
Learning outcome 12.4(b)
This statement is about the use of cisplatin as an anti-cancer drug. This is new to the 2016 syllabus, and it is uncertain at the moment what sort of depth of knowledge they expect.
Before you go on, you should find and read the statement in your copy of the syllabus.
Cisplatin has the formula Pt(NH3)2Cl2. There are two completely different ways in which the ammonias and chloride ions could arrange themselves around the central platinum ion, and one of these is the cis-form which we are interested in:
Cisplatin is an anti-cancer drug, and can pass through cell membranes. Once it is in the cell, the concentration of chloride ions is much less than it is outside the cell, and you get a ligand exchange reaction where the chlorines are replaced by water molecules.
The water molecules are bound to the platinum more loosely than the chlorines were.
Cisplatin works by attaching itself to DNA in such a way that stops it functioning properly.
The two strands of DNA are held together by hydrogen bonding between "base pairs". The diagram shows a tiny bit of a DNA double helix.
Note: This diagram comes from the US National Library of Medicine. You can see it in its original context by following this link if you are interested.
Normally I prefer to draw my own diagrams, but my drawing software isn't sophisticated enough to produce convincing twisted "ribbons".
Cisplatin has the ability to bond to two of these bases - guanine and adenine.
The water molecules currently bound to the platinum fall off, and co-ordinate bonds (dative covalent bonds) to the platinum are formed using a lone pair on a nitrogen atom of two guanines next door to each other in the helix.
That kinks the helix and wrecks the function of the DNA in the cell, which then dies.
There is a simple YouTube video showing this in more detail than you actually need.
Note: There is quite a lot wrong with this video from a chemistry point of view.
You can almost certainly ignore the action of the protein shown in the animation - you are doing A level chemistry, not degree level biology or biochemistry!
The video skips over the initial replacement of the chlorines by water.
And it gives the impression that a bond is formed from the platinum to the nitrogen, rather than the other way around. These should be co-ordinate bonds using the lone pair on a nitrogen atom attaching to an empty orbital on the platinum.
It does, however, save me having to draw a whole lot of very complicated diagrams!
Transplatin, where the chlorines are opposite each other, can't interfere with DNA in the same way because the geometry is wrong.
Cisplatin has major side-effects because, of course, it doesn't only attack the DNA in cancer cells.
© Jim Clark 2014