Metal Chelation

Question 1

What are hard and soft metals?

Answer 1

Hard = gp 1 and 2 - interactions with organic molecules = completely electrostatic - don't deform from a sphere.
Soft = large metals (electron cloud can deform) - low chage density - bind sulphur atoms by covalent bonds.

Question 2

How can we determine ligand selectivity?

Answer 2

Surface charge - related to charge density = charge / area.

Question 3

Give four examples of toxic ligands.

Answer 3

Pb(II) - binds to iron metalloproteins.
Cadmium(II) - binds zinc metalloproteins.
Aluminium (III) - binds iron and calcium binding sites
Mercury (II) - binds zinc metalloproteins.

Question 4

What are the ideal requirements for an iron chelator?

Answer 4

Oral activity
Minimal metalloenzyme inhibition
No redox cycling
Ligand and iron complex penetrate BBB
Selective for iron.

Question 5

What chelator has been investigated for the treatment of Parkinson’s disease?

Answer 5

DFO (doesn’t cross BBB)
Deferiprone - Clinical trials in Lille and UK. Both showed;
- Low dose improving motor and mental response
- removes iron from SN
- After 3 weeks treatment - all patients = more relaxed!

Question 6

What shape complexes are formed by; Zn(II), Fe(II), Cu(II), Pt(II).

Answer 6

terahedral
Ocatahedron
Deformed octahedron or square pyramid (5 ligands)
Square planar.

Question 7

What else can iron chelators be used for?

Answer 7

Antibacterials

Chemotherapy.

Question 8

What is special about Salmonella?

Answer 8

Most siderophores have unique transport system so can’t be used by other organisms.
Salmonella expresses a wide range of receptors so can use the siderophores of competing organisms.

Question 9

what is the scale of the problem with haemoglobinopathies?

Answer 9

~7% of world’s population are carriers.

350,000,000 people.