Chirality & Drug Production (CIE A Level Chemistry)

• Most of the drugs that are used to treat diseases contain one or more chiral centres
• These drugs can therefore exist as enantiomers which differ from each other in their ability to rotate plane polarised light
• Another crucial difference between the enantiomers is in their potential biological activity and therefore their effectiveness as medicines
• Drug compounds should be prepared in such a way that only one of the optical isomer is produced, in order to increase the drugs’ effectiveness
  • Some drug enantiomers can have very harmful side effects

Potential biological activity of enantiomers

• If conventional organic reactions are used to make the desired drug, a racemic mixture will be obtained
  • In a racemic mixture, there are equal amounts of the two enantiomers

• The physical and chemical properties of the enantiomers are the same, however, they may have opposite biological activities
• For example, the drug naproxen is used to treat pain in patients that suffer from arthritis
  • One of the enantiomers of naproxen eases the pain, whereas another enantiomer causes liver damage

• One enantiomer of a drug used to treat tuberculosis is effective whereas another enantiomer of this drug can cause blindness
• Thalidomide is another example of a drug that used to be used to treat morning sickness, where one of the enantiomers caused very harmful side effects for the unborn baby

Separating racemic mixtures

• Due to the different biological activities of enantiomers, it is very important to separate a racemic mixture into pure single enantiomers which are put in the drug product
• This results in reduced side-effects in patients
  • As a result, it protects pharmaceutical companies from legal actions if the side effects are too serious

• It also decreases the patient’s dosage by half as the pure enantiomer is more potent and therefore reduces production costs
  • A more potent drug has a better therapeutic activity

Chiral catalysts

• In order to produce single, pure optical isomers, chiral catalysts can be used
• The benefits of using chiral catalysts are that only small amounts of them are needed and they can be reused
  • For example, an organometallic ruthenium catalyst is used in the production of naproxen which is used in the treatment of arthritis

The organometallic ruthenium catalyst is a chiral catalyst which ensures that only one of the enantiomers is formed which can be used in treating arthritis

• Enzymes are excellent biological chiral catalysts that promote stereoselectivity and produce single-enantiomer products only
  • Stereoselectivity refers to the preference of a reaction to form one enantiomer over the other

• Due to the specific binding site of enzymes, only one enantiomer is formed in the reaction
• The enzymes are fixed in place on inert supports so that the reactants can pass over them without having to later separate the product from the enzymes
• The disadvantage of using enzymes is that it can be expensive to isolate them from living organism
  • Therefore, more research has recently been carried out into designing synthetic enzymes

• Although using enzymes to produce pure enantiomers in drug synthesis takes longer than conventional synthetic routes, there are many advantages to it in the long run
  • For example, using enzymes to synthesise drugs is a greener process as fewer steps are involved compared to conventional synthetic routes