Chemotherapy

Platinum retention times are different in different organs, decreasing in the

order kidney > liver > genitals > spleen > bladder > heart > skin > stomach >
brain. After interaction with the DNA in the cells of these organs, the
degradation products are excreted via the liver and kidney.
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Chemotherapy

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Chemotherapy

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Chemotherapy

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 Chemotherapy

1. Electron transfer

Excess cellular levels of ROS cause damage to proteins, nucleic acids, lipids, membranes and
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organelles, which can lead to activation of cell death processes such as apoptosis.
 Chemotherapy

1. Electron transfer

Excess cellular levels of ROS cause damage to proteins, nucleic acids, lipids, membranes and
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organelles, which can lead to activation of cell death processes such as apoptosis.
 Chemotherapy

2. Covalent binding

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 Chemotherapy
3. Electrostatic binding

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 Chemotherapy

4. Hydrolysis

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 Chemotherapy
4. Hydrolysis

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 Chemotherapy
4. Hydrolysis

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 Differences Organic and Inorganic Drugs
• Easy one-electron reductions possible with many metal ions;

• Easy changes in structure due to

metal-ligand dissociation reactions:
use as pro-drugs; kinetic differences are metal dependent.

• Metal ions as such are non-degradable

 Two major types of metal drugs

• Drugs with slow metals (like Ru, Pt) or slowly

exchanging chelating ligands, like porphyrins;

• Drugs with rapid metals (fast ligand

exchanges, on cellular/biological time scales).
Why Platinum is so good?
And why are other metals
less good?

The secret is the speed of

its reactions – a.o. with
DNA – compared with the
speed of cell divisions!
Hard (A) to Soft (class B) ions

Hg2+ 2+
Ru2+ Pt Pt4+ Ir3+
2+
Cd Ru3+
Pd2+
Zn2+ Co2+
Cu2+
Fe2+ Co3+
Ni2+ Cr 3+
Ln3+ V2+
Cs+ 2+
Ca In3+
Mn2+ Be2+
Na+ Mg 2+ Ga3+ Al3+
Li+

10+8 10+6 10+4 10+2 100 10-2 10-4 10-6

Decreasing rate of aqua ligand exchange in s-1

 Ligand Exchange Kinetics
How fast (16OH2) exchanges with (18OH2) at a
particular metal site

Mn2+
Range Pt2+ Ru2+ Pd2+Ni2+Fe2+Zn2+ Cu2+
of cell Co2+
division
Ir3+ Rh3+ Cr3+Ru3+ Fe3+V3+ Ti3+

10years 1 day 1 hour 1s 1 ms 1 μs 1 ns

200 years