Optical Isomerism

1. Optical isomerism arises in organic molecules that contain a carbon atom attached to 4 different atoms or groups. • A carbon with 4 different atoms or groups attached is called a chiral centre. • If a molecule has a chiral centre in its structure, two mirror image arrangements are possible in space. They are non-superimposable mirror images of each other: they are optical isomers. Optical Isomerism Chiral Carbon attached to 4 different atoms or groups. • Optical isomers rotate plane polarised light in opposite directions: one rotates light clockwise and the other anticlockwise. • A mixture containing equal amounts of each isomer is known as a racemic mixture. A racemic mixture has no effect on plane polarised light because the rotations cancel each other out.

2. Chirality in Pharmaceutical Synthesis • Why is chirality in drug synthesis important? • The drug Thalidomide was prescribed during the 50s and 60s to prevent morning sickness in pregnant women. The drug was a chiral compound: • One of the stereoisomers has the desired therapeutic effect • The other stereoisomer led to deformities in developing babies. The production of a single isomer with the correct pharmacological activity presents 2 main advantages to pharmaceutical companies.: Risks from undesirable side effects are reduced: if thalidomide has been used as the ‘correct’ single optical isomer, morning sickness would have been prevented without the deformities caused by the other optical isomer. Drug doses are reduced: often when racemic mixtures are given as drugs, half of the dosage is wasted because only 1 of the isomers has the desired therapeutic effect. Making a drug containing only the one optical isomer should reduce the desired dose by half. Biological molecules have complex three dimensional structures that bind to a drug molecule in only one possible way. The 3D structure of a drug determines its pharmacological activity and whether it will have the desired therapeutic effect or not.

3. Chirality in Pharmaceutical Synthesis After preparing a chiral compound in the lab, complicated separation techniques are required to isolate the pharmacologically active isomer. Separation is difficult because optical isomers tend to have the same physical properties – melting points, boiling points and solubilities. Separation techniques often include the use of enzymes, electrophoresis and chromatography. This takes lots of time and is expensive. When a chiral compound is synthesised in the lab, a mixture of optical isomers is usually formed. When the same material is made naturally in a living system, it is produced as a single optical isomer. • Modern Chiral Synthesis: there are a number of methods being used or developed to prepare single chiral isomers: • Using enzymes as biological catalysts: nature is good at making single optical isomers • Chiral Pool Synthesis: this uses naturally occurring chiral molecules within the synthetic route such as α-amino acids and sugars. • Using transition element complexes to produce chiral catalysts which could transfer their chirality to produce a single isomer product.