Inorganic chemistry

Question 1

Which other metals have some anti-cancer activity but not enough for clinical trials?

Answer 1

Gallium
Hafnium
Palladium
Gadolinium

Question 2

What metal is used in the treatment of rheumatoid arthritis?

Answer 2

Gold

- sodium aurothiomalate

Question 3

What is a metalloid?

Answer 3

Type of chemical element which has a preponderance of properties in between, or that a mixture of, those of metals or non-metals

Question 4

What are boronic acids considered to be?

Answer 4

Lewis acids

pKa 4 - 10

Question 5

What is the effect on Pka when adding an electron withdrawing group to aromatic boronic acid?

Answer 5

pKa decreases

Question 6

What effect on Pka does adding an electron donating group to aromatic boronic acid?

Answer 6

pKa increases

Question 7

What form/shape are boronic acids in at physiological pH?

Answer 7

Trigonal form

Question 8

What form are boronic acids in in aqueous solutions with pH values higher than pKa?

Answer 8

Anionic tetrahedral forms

Question 9

What was the first in-class proteasome inhibitor as well as the first boron-containing anti-cancer drug?

Answer 9

Bortezomib

Question 10

What is Bortezomib used to treat?

Answer 10

Multiple myeloma

- white blood cell cancer

Question 11

What is the structure of Bortezomib?

Answer 11

Pseudo-peptide that inhibits the proteasome
- cellular protein complex involved in protein degradation
In some cancers, the proteins that normally kill cancer cells are broken down too quickly
- Bortezomib interrupts this process and allows those proteins kill the cancer cells

Question 12

How does Bortezomib work?

Answer 12

The boronic acid group is key to proteasome binding

• can form hydrogen bonds
• enhances the interactions between Bortezomib and the protein
• shows a different spatial arrangement when compared with a carboxylic acid
• tetrahedral vs trigonal planar

Question 13

What is the difference between ibuprofen and sila-ibuprofen?

Answer 13

Sila-ibuprofen has similar binding characteristics and a similar inhibitory profile towards COX-1 and COX-2 as ibuprofen
- higher solubility

Question 14

What is the therapeutic index?

Answer 14

Maximum tolerated dose / minimum curative dose

Question 15

What are chelates?

Answer 15

Complex ions which form co-ordinate bonds in which both electrons originate from the same atom
- dative bond

Question 16

When does a typical chelate form?

Answer 16

When one or more organic molecules form coordinate bonds to a metal atom

• haem is a good example
• iron ion co-ordinated to a porphyrin ring acting as a tetradentate ligand and to one or two axial ligands

Question 17

What is chelation therapy?

Answer 17

A medical procedure that involves the intravenous administration of chelating agents to remove heavy metals from the body

• lead
• mercury
• arsenic

Question 18

How does chelation therapy lead to deficiency diseases?

Answer 18

Chelating drugs can bind to remove some metals your body needs

• calcium
• copper
• zinc

Question 19

How do isoniazid and ethambutol work?

Answer 19

Dependent on copper chelation for activity

Question 20

What does copper form chelates with?

Answer 20

Electron rich atoms

• O
• N

Question 21

How does copper change the lipophilicity of drugs?

Answer 21

Copper masks that polarity of electron rich atoms, making the complex is more lipophilic and facilitates concentration within the bacterial cell

Question 22

Which metal does tetracycline rely on?

Answer 22

Magnesium

Question 23

Why is magnesium-tetracycline chelate advantageous?

Answer 23

More lipophilic than the drug alone and penetrate biological barriers more easily