Enantiomers and optical isomerism

· Enantiomers = two optical isomers that are non-superimposable mirror images of each other.
· Enantiomers usually arise when a molecule contains a chiral centre: a carbon atom bonded to four different groups.
· Enantiomers have the same structural formula and the same connectivity, but a different 3D arrangement.
· Enantiomers have identical physical properties such as melting point, boiling point and solubility, except for their effect on plane-polarised light.
· Enantiomers usually have identical chemical properties in non-chiral conditions.
· In chiral biological systems, enantiomers may behave very differently because enzymes and receptors are themselves chiral.

Enantiomers are mirror images that cannot be placed exactly on top of each other. This non-superimposable relationship is the key feature of optical isomerism. Source

Plane-polarised light and optical activity

· Plane-polarised light = light vibrating in one plane only.
· A substance is optically active if it rotates plane-polarised light.
· One enantiomer rotates plane-polarised light clockwise; this is often described as dextrorotatory or +.
· The other enantiomer rotates plane-polarised light anticlockwise by the same angle; this is often described as laevorotatory or −.
· For a single substance, the two enantiomers rotate plane-polarised light by equal amounts in opposite directions.
· The direction of rotation cannot be predicted from structure alone at A-Level; it must be found experimentally.

Racemic mixtures

· A racemic mixture contains equal amounts of both enantiomers of a chiral compound.
· A racemic mixture is optically inactive because the rotations caused by the two enantiomers cancel out.
· Example idea: if one enantiomer rotates light by +x°, the other rotates it by −x°; a 50:50 mixture gives 0° overall rotation.
· Racemic mixtures are common when a chiral product is made using non-chiral reagents or conditions, because both enantiomers may form in equal amounts.
· A racemic mixture may need to be separated into pure enantiomers if only one enantiomer has the desired biological effect.

A racemic mixture contains equal amounts of both enantiomers. Their equal and opposite rotations cancel, so the mixture is optically inactive. Source

Enantiomers in drug molecules

· Chirality is highly relevant in drug synthesis because many biological targets, such as enzymes and receptors, are chiral.
· Two enantiomers of the same drug can have different biological activity.
· One enantiomer may be therapeutically useful, while the other may be less active, inactive, or may cause different side effects.
· This happens because each enantiomer has a different 3D fit with a chiral active site or receptor.
· Exam phrase: same chemical formula, different spatial arrangement, different interaction with biological receptors.

Chiral drug molecules can interact differently with biological targets. This explains why two enantiomers may have very different effects in the body. Source

Making pure optical isomers in synthesis

· Drug synthesis may produce a racemic mixture, but often only one enantiomer is wanted.
· A racemic mixture may need to be resolved, meaning the two enantiomers are separated.
· Separating enantiomers is difficult because they have very similar physical and chemical properties in non-chiral environments.
· A better method is often to use a chiral catalyst to make mainly or only one pure optical isomer.
· Chiral catalysts provide a chiral environment, favouring formation of one enantiomer over the other.
· This is important in pharmaceuticals because it can increase efficacy, reduce unwanted effects, and reduce waste from unwanted enantiomers.

Chiral catalysts help direct a reaction to form one enantiomer preferentially. This is useful when a drug must be made as a single pure optical isomer. Source

Common exam traps

· Do not say enantiomers have completely different physical properties; they have identical physical properties except optical rotation.
· Do not say a racemic mixture has no enantiomers; it contains both enantiomers in equal amounts.
· Do not say a racemic mixture is optically active; it is optically inactive because rotations cancel.
· Do not assume + / − optical rotation tells you the exact 3D arrangement unless data is given.
· Do not discuss meso compounds or diastereoisomers unless given in the question; these are not required for this syllabus point.