Monthly Archives:: November 2015

Molecule of the Week

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Wilkinson’s Catalyst

Wilkinson's Catalyst

Indeed, Wilkinson’s catalyst is a pre-catalyst that is converted to an active form by losing one triphenylphosphine ligand before entering the catalytic cycle. Usually, the solvent molecule fills the vacant site.

Initially, the catalyst activates the molecular dihydrogen by oxidative addition mechanism to give a 18 valence electron dihydrido complex. The oxidation state of Rh is increased to +3. Thus formed dihydrido complex binds to the olefin in the next step with the concomitant loss of solvent or PPh3 ligand. Since the activation of dihydrogen occurs before addition of olefin, this path is referred to as dihydride path .

Now one of the hydrogen undergoes migratory insertion at the double bond. This is a slow step i.e., Rate Determining Step (RDS).

Immediately and finally, the alkane is released rapidly by an irreversible reductive elimination step that completes the catalytic cycle. The oxidation state of Rh is decreased to +1 and the catalyst is regenerated.

However, other paths and intermediates are also possible under the given reaction conditions (see link below).

How does the catalytic reaction work?

When it is dissolved in a solvent like benzene-ethanol, one of the phosphine molecules can be replaced by a weakly-bound solvent molecule, giving what is effectively a three-coordinate rhodium complex. Under an atmosphere of hydrogen gas, the resulting complex adds a hydrogen molecule, breaking the H-H bond forming a five-coordinate dihydride complex of rhodium. The dihydride is a Rh(III) species, so this is an oxidative-addition reaction, during which the colour of the solution changes from red to yellow. [RhH2Cl(PPh3)2] is still a 16-electron species and also has a vacant coordination site, so it can add an alkene molecule, forming a six-coordinate 18-electron complex. Next, there is a rearrangement with the coordinated alkene being inserted into a rhodium-hydrogen bond to form an alkyl complex – alternatively, think of it as a hydride transfer to the coordinated alkene. This step is rapidly followed by the transfer of the other hydrogen from rhodium to the alkyl group. This generates an alkane, which is immediately lost in a reductive-elimination step, so that the catalytic cycle – shown below in simplified form – can begin again.



Molecule of the Week

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Pioglitazone; The Molecule of the Week

Pioglitazone is a thiazolinedione drug that reduces blood glucose levels in diabetic patients. Takeda Pharmaceuticals launched it under the trade name Actos in 1999. Within 10 years, it became the world’s best-selling diabetes drug. Although it is relatively safe, some countries have stopped its sale because it is associated with bladder tumors.

As indicated in the images, pioglitazone is a racemic mixture of two enantiomers. Because the enantiomers interconvert in vivo, no differences are seen between the two in terms of pharmacological activity.


In 2015, Stéphane Prost, Philippe Leboulch, and colleagues at the Institute of Emerging Diseases & Innovative Therapies in France and Harvard Medical School discovered that pioglitazone can work with the cancer drug imatinib so that it not only stops the spread of chronic myeloid leukemia but eliminates the cancer altogether. Cancer stem cells can “hide” from imatinib by becoming quiescent, but pioglitazone releases the cells from “hibernation” to allow the cancer drug to finish its job. The researchers are preparing for clinical trials on pioglitazone.

More about this molecule from CAS, the most authoritative and comprehensive source for chemical information.



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