Inorganic chemistry Flashcards
Which other metals have some anti-cancer activity but not enough for clinical trials?
Gallium
Hafnium
Palladium
Gadolinium
What metal is used in the treatment of rheumatoid arthritis?
Gold
- sodium aurothiomalate
What is a metalloid?
Type of chemical element which has a preponderance of properties in between, or that a mixture of, those of metals or non-metals
What are boronic acids considered to be?
Lewis acids
pKa 4 - 10
What is the effect on Pka when adding an electron withdrawing group to aromatic boronic acid?
pKa decreases
What effect on Pka does adding an electron donating group to aromatic boronic acid?
pKa increases
What form/shape are boronic acids in at physiological pH?
Trigonal form
What form are boronic acids in in aqueous solutions with pH values higher than pKa?
Anionic tetrahedral forms
What was the first in-class proteasome inhibitor as well as the first boron-containing anti-cancer drug?
Bortezomib
What is Bortezomib used to treat?
Multiple myeloma
- white blood cell cancer
What is the structure of Bortezomib?
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
How does Bortezomib work?
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
What is the difference between ibuprofen and sila-ibuprofen?
Sila-ibuprofen has similar binding characteristics and a similar inhibitory profile towards COX-1 and COX-2 as ibuprofen
- higher solubility
What is the therapeutic index?
Maximum tolerated dose / minimum curative dose
What are chelates?
Complex ions which form co-ordinate bonds in which both electrons originate from the same atom
- dative bond
When does a typical chelate form?
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
What is chelation therapy?
A medical procedure that involves the intravenous administration of chelating agents to remove heavy metals from the body
- lead
- mercury
- arsenic
How does chelation therapy lead to deficiency diseases?
Chelating drugs can bind to remove some metals your body needs
- calcium
- copper
- zinc
How do isoniazid and ethambutol work?
Dependent on copper chelation for activity
What does copper form chelates with?
Electron rich atoms
- O
- N
How does copper change the lipophilicity of drugs?
Copper masks that polarity of electron rich atoms, making the complex is more lipophilic and facilitates concentration within the bacterial cell
Which metal does tetracycline rely on?
Magnesium
Why is magnesium-tetracycline chelate advantageous?
More lipophilic than the drug alone and penetrate biological barriers more easily
