Stereoisomerism is a type of isomerism in which molecules have the same molecular formula and the same structural (connectivity) formula but differ in the three-dimensional spatial arrangement of their atoms.
Stereoisomers are divided into two main categories:
Geometrical isomerism arises in alkenes due to restricted rotation about the double bond.
Why is rotation restricted? The double bond consists of:
Rotation about the double bond would require breaking the bond, which needs significant energy. Therefore, rotation is effectively prevented at room temperature.
Conditions for cis-trans isomerism in alkenes:
Example: 2-Butene ()
| Isomer | Description |
|---|---|
| cis-2-butene | Both groups on the same side of the double bond |
| trans-2-butene | Both groups on opposite sides of the double bond |
Note: 1,1-Dichloroethene () does not show cis-trans isomerism because one carbon of the double bond carries two identical substituents ( and ).
Geometrical isomerism also occurs in square planar and octahedral transition metal complexes.
Example:
The two isomers have different physical and biological properties.
Example 1:
Example 2: (Ni with two en ligands and two water)
Here, the bidentate ligand 1,2-diaminoethane (en) occupies two adjacent coordination sites. The two molecules can be:
A chiral centre is a carbon atom bonded to four different atoms or groups. Such a molecule is non-superimposable on its mirror image.
Example: Lactic acid () — carbon-2 is bonded to , , , and .
Enantiomers are a pair of optical isomers that are non-superimposable mirror images of each other. They:
A racemic mixture (racemate) is an equimolar mixture of two enantiomers. It is optically inactive because the equal and opposite rotations of the two enantiomers cancel each other out.
Octahedral complexes with bidentate ligands can also show optical isomerism.
Example: (Ni with three en ligands)
The three bidentate en ligands wrap around the Ni ion in a propeller-like arrangement. The two non-superimposable mirror image forms are optical isomers (enantiomers).
Example: (cis isomer only)
The cis isomer of this complex is chiral and exists as a pair of enantiomers. The trans isomer has a plane of symmetry and is optically inactive.
Chirality is critically important in pharmaceutical chemistry because enantiomers can have very different biological activities.
Biological receptor sites are themselves chiral (made of chiral amino acids). Only the enantiomer with the correct three-dimensional shape will fit the receptor site and produce the desired effect — like a hand fitting a glove.
Thalidomide () was prescribed in the late 1950s as a sedative and anti-nausea drug for pregnant women. It was sold as a racemic mixture.
| Enantiomer | Effect |
|---|---|
| -thalidomide | Effective sedative |
| -thalidomide | Teratogenic — causes severe limb deformities in developing fetuses |
The tragedy resulted in thousands of babies being born with limb defects.
Important note: Even administering pure -thalidomide is not safe, because in the body it undergoes racemisation — it is converted back to a mixture of both enantiomers. Therefore, the -isomer will always be produced in vivo.
1. Chiral Resolution (Separation of Enantiomers)
Enantiomers cannot be separated by ordinary physical methods (same boiling point, solubility, etc.). They are separated by:
2. Chiral Catalysts
A chiral catalyst can be used during synthesis to produce predominantly or exclusively one enantiomer (asymmetric synthesis). This avoids the need for separation and is more efficient.
Advantages of producing a single pure enantiomer: