Transition metals: Cisplatin, haemoglobin, EDTA.

Edexcel A level Chemistry (2017)

Topic 15A: Principles of transition metal chemistry

Learning Objectives related to cis-platin and haemoglobin function

15/15. To know that square planar complexes are also formed by transition metal ions and that cis-platin is an example of such a complex.

15/16. To understand why cis-platin used in cancer treatment is supplied as a single isomer and not in a mixture with the trans form.

15/17. To be able to identify bidentate ligands, such as NH2CH2CH2NH2 and multidentate ligands, such as EDTA4− .

15/18. To know that haemoglobin is an iron(II) complex containing a multidentate ligand.

The structure of the haem group will not be assessed.

15/19. To know that a ligand exchange reaction occurs when an oxygen molecule bound to haemoglobin is replaced by a carbon monoxide molecule.

Cis-Platin and Haemoglobin

Let’s look first at cis-platin (cis-Pt(NH₃)₂Cl₂:

This is its structure.  You’ll see that it is a square planar shape and that the two chloro ligands sit on one side of the complex and two ammine ligands on the other side.

So the ligands are cis to each other like in alkene cis isomers where the two functional groups are on the same side of the carbon—carbon double bond. 

In its isomer trans–platin, the chloro and ammine ligands sit across from each other. 

Cis-platin is used in cancer treatment. 

I remember this well because my lab technician, a brilliant person and great support Val, sadly went down with peritoneal cancer back in the day and her treatment included cis-platin.  For over two years it kept her well and working for us it was the best thing to do under the circumstances she would say despite us saying to her to take a day off whenever she needed to. 

The role of cis-platin is not that well understood as to why it inhibits the growth of cancer cells.  It may have something to do with the reactivity of the chloro groups that might undergo a ligand exchange reaction with groups on the DNA of cancer cells and impede DNA replication.  It is this that might interrupt cell growth. 

The trans isomer has no effect on cancer cells so the drug is supplied in the cis form only. 

Haemoglobin

Haemoglobin is the molecule responsible for the carrying of oxygen around the human body.

It is responsible for the red colour of blood and red blood cells.

Heamoglobin has a quaternary structure in which four myoglobin proteins are bonded together.  You can see the four myoglobin molecules in the four different colours in the diagram above.

Note too that each myoglobin has at its centre an iron ion surrounded by a haem structure.  The haem structure is shown below:

We can see that the haem group is a multidentate ligand where in this case four bonds form with the iron ion. 

The iron ion (Fe²⁺) is at the centre of four nitrogen atoms.  There is another nitrogen below the iron ion (see the diagram below).  

The last bond is available to bond to oxygen.  This allows the myoglobin to carry oxygen gas around the body in oxygenated blood and release the oxygen where it might be needed.  

In other words, the attachment of oxygen to the haem iron is reversible.  This is illustrated in the diagram below. 

If the blood is exposed to carbon monoxide however the oxygen ligand is exchanged for a carbon monoxide ligand.   

The bond formed with iron becomes so strong that the attachment of carbon monoxide is irreversible.  

As no oxygen can be taken up asphyxiation is the result.  The blood turns a pink colour.

Other multidentate ligands

Other multidentate ligands include the bidentate ligand NH₂CH₂CH₂NH₂  1,2–diaminoethane and the hexa-dentate ethylene diammine tetraacetic acid EDTA.

Here are typical complex ion structures with these two multidentate ligands. 

In an EDTA complex, the hexadentate ligand can wrap itself around the central metal ion and create a chelate the process known as chelation.  See the diagram above.

A bidentate ligand bonds at two points to a transition metal ion as in the diagram below.  Each nitrogen atom has a lone pair available to make the dative covalent bond with the transition metal cation.

You can also see that the structures are mirror images of each other giving rise to optical isomers.