Introduction
Stereochemistry studies molecules that share the same connectivity (which atoms are bonded to which) but differ in their three-dimensional spatial arrangement — a distinction invisible in an ordinary structural formula but often critical to a molecule’s chemical and biological behaviour (most dramatically, in drugs where one stereoisomer is therapeutic and its mirror image is inactive or harmful).
1. Chirality and stereogenic centres
A molecule is chiral if it is non-superimposable on its mirror image (like a left and right hand). The most common source of chirality is a stereogenic centre (commonly a carbon bonded to four different groups), though chirality can also arise from other structural features. A molecule with an internal plane of symmetry cannot be chiral even if it contains apparent stereogenic centres, because such a molecule is superimposable on its mirror image (an achiral, or meso, compound).
2. Enantiomers and diastereomers
Enantiomers are non-superimposable mirror images of each other — they have identical physical properties (melting point, boiling point, solubility) except for how they rotate plane-polarised light (opposite directions, equal magnitude) and how they interact with other chiral molecules or environments (such as biological receptors, which is why enantiomers can have very different biological effects). Diastereomers are stereoisomers that are not mirror images of each other (arising when a molecule has more than one stereogenic centre) — unlike enantiomers, diastereomers have genuinely different physical properties and can, in principle, be separated by ordinary means like distillation or crystallisation.
3. Optical activity
A chiral compound rotates the plane of plane-polarised light passing through it — this optical activity is measured with a polarimeter and is how enantiomers are experimentally distinguished, since all their other physical properties are identical. A 50:50 mixture of both enantiomers (a racemic mixture) shows no net optical rotation, because the equal and opposite rotations from each enantiomer cancel.
4. R/S configuration
The Cahn–Ingold–Prelog (CIP) rules assign priority to the four groups on a stereogenic centre based on atomic number (and, where needed, further rules for ties), then designate the configuration R (clockwise priority sequence, viewed with the lowest-priority group pointing away) or S (counterclockwise) — this is a systematic, unambiguous way to specify a molecule’s three-dimensional configuration in its name, independent of how the direction of optical rotation happens to be measured experimentally (there is no simple predictive relationship between R/S designation and the direction of optical rotation).
5. Geometrical isomerism and conformational ideas
Geometrical (cis/trans, or E/Z) isomerism arises from restricted rotation, most commonly around a C=C double bond (Chapter 12) or in ring systems, where substituents can be arranged on the same side (cis/Z, generally) or opposite sides (trans/E) of the restricted bond or ring. Conformational isomers (conformers), by contrast, interconvert freely by rotation around single bonds at room temperature (such as the staggered and eclipsed forms of ethane) and are not usually isolable as separate compounds — the distinction between configurational isomerism (fixed, requiring bond-breaking to interconvert: enantiomers, diastereomers, cis/trans) and conformational isomerism (freely interconverting) is essential to keep clear.
Key Takeaways
- Chirality (non-superimposable mirror images) most commonly arises from a stereogenic centre; a molecule with an internal symmetry plane is achiral even with apparent stereocentres present (meso compounds).
- Enantiomers share all physical properties except optical rotation direction and interaction with other chiral entities; diastereomers genuinely differ in physical properties and are separable by ordinary methods.
- Optical activity, measured by a polarimeter, is how enantiomers are experimentally distinguished; a racemic mixture shows zero net rotation.
- CIP rules assign unambiguous R/S configuration labels based on group priority, independent of the (unrelated) direction of optical rotation; configurational isomerism (fixed) is fundamentally different from freely interconverting conformational isomerism.