CHEMS305F

Exercise Set Three Solution

Question 1
The following compound, desferrioxamine B, is used as a drug to treat iron overload in patients.

i) Based on the chemical structure of desferrioxamine B, identify and circle the donor atoms
available to coordinate Fe(III) in solution.
Answer
DFO-B has oxygen donor atoms from N-hydroxyl and amide.

ii) How many donor atoms of the ligand can be coordinated on Fe(III)?
Answer six
Page 1

iii) The formation constant for desferrioxamine B with Fe(III) ion is 1030.6. Write an equilibrium
equation and expression of the formation of Fe(III) desferrioxamine complex.
Answer
Fe3+ + H3DFO-B

[Fe(III) (DFO-B)] + 3 H+

[FeIII (DFO - B)][H ]3

Kf =
= 1030.6
III
[Fe ][H3DFO - B]

iv) Comment on the stability of the Fe(III) desferrioxamine complex and hence explain why
desferrioxamine B could be used to treat iron overload.
Answer
The formation constant for Fe(III) desferrioxamine complex is high
Keq = 1030.6 which implies that the Fe(III) desferrioxamine is thermodynamically very stable.
The desferrioxamine B has a high tendancy to form complex with Fe(III) in body.
Thereby helping to remove excess Fe3+.
v) Briefly describe the effect of a decrease in pH on the stability of the Fe(III) desferrioxamine
complex.
Answer
A decrease in pH would decrease the stability of the Fe(III) desferrioamine complex
because the ligand N-O- would be protonated and reduce its affinity to Fe(III) at low pH
vi) Drugs with high selectivity may have fewer side-effects. Briefly explain why DFO-B is
selective for Fe(III), but not dipositive transition metal ions and heavy metal ions.
Answer
DFO-B has three oxide donor atoms which can fit M3+ but not M2+.
Oxygen is hard donor atom and the affinity for late transition metal ions (heavy) is lower.

Page 2

Question 2
Zinc is an essential trace element for human, plants, animals and microorganisms. In most
organisms, it is the second most abundant transition metal in the biological system after iron and it is
the only metal which appears in all enzyme classes. One of the Zn containing enzyme is carbonic
anhydrase (CA). The CA catalyzes the reaction between carbon dioxide and water to form hydrogen
carbonate at physiological condition. The Zn(II) active site of CA is shown below:

a)

Write down the electronic configuration of Zn.

Answer [Ar]4s23d10

b)

Do you considered zinc metal a transition metal? Briefly explain your answer.
Answer No. The definition of transition metal is that the atom contain a partially filled d-orbital.
Since the electronic configuration of zinc is [Ar]4s23d10, it has a full filled d subshell and
therefore, it is not a transition metal.

c)

The spectroscopic study of Zinc containing enzyme is of great difficulty. Suggest a reason for
this.
Answer the most common oxidation state of Zn is Zn(II). It has an electronic configuration of
3d10 and the complexes are normally colorless and diamagnetic. Therefore, it is difficult to
analyze Zn containing enzyme through the UV spectroscopy or through the study of magnetic
moments.

d)

Discuss the mechanism of carbonic anhydrase and briefly describe the role of Zn(II) in the
active site.
Answer: the chart below starts from item (A)

Page 3

Zinc(II) is a good Lewis acid because high charge/radius ratio

The water coordinated to Zn(II) is readily converted to OH- by release of one proton
The OH- subsequently reacts with CO2 to form carbonate.
Since Zn is able to convert H2O to OH- at pH7 (physiological condition), therefore, it catalyzes the
reaction of CO2 and water to form HCO3-.
e)

The zinc(II) ion in carbonic anhydrase can be substituted by the first row transition metal ions
and the activity of the metal-substituted enzyme could then be measured. The trend of enzymic
activity to catalyze the converstion of CO2 to HCO3- is shown below:
Zn(II) > Co(II) > Ni(II) Cu(II)
Briefly explain the trend in enzymic activity.
[Hint: You should consider the common coordination geometry of the metal ions]
Answer
In the catalytic cycle of carbonic anhydrase, one of the key intermediate is the metal bounded
hydrogen carbonate.
For the catalytic cycle to be completed, the hydrogen carbonate must be displaced by water.
However, if the hydrogen carbonate is coordinated to the metal ion in a bidendate mode, the
displacement by water will be much difficult.
Whether the hydrogen carbonate acts as a monodendate or bidendate ligands depends on the
common coordination geometry of the metal ions.
Both Cu(II) and Ni(II) ion will preferably form the bidendate complex
Page 4

because these two metals are six-coordinate complexes.

For Zn(II), the most common geometry is tetrahedral.
Therefore, the hydrogen carbonate ion is coordinated to Zn(II) as a monodendate ligand
and could be easily displaced by water in the final step of the catalytic reaction.
For Co(II), it can adopt either tetrahedral or 5/6 coordination geometry.
Therefore, the reactivity of Co(II) would be in the middle.

[END OF Exercise three]

Page 5