29.4 Optical isomerism

Enantiomers are non-superimposable mirror images. In an achiral environment they have the same melting point, boiling point and many chemical properties, but they rotate plane-polarised light in opposite directions.

A chiral receptor or enzyme is itself asymmetric, so the two enantiomers can bind differently and produce different biological effects.

Two enantiomers may pass through an ordinary solvent identically yet one fit a biological active site better, like opposite hands fitting a glove.

R and S labels do not by themselves tell you clockwise optical rotation, and “same formula” does not mean the molecules are superimposable.

An optically active sample rotates plane-polarised light. A racemic mixture contains equal amounts of both enantiomers, whose opposite rotations cancel, so the mixture shows no net rotation.

Optical activity describes the sample, not simply the presence of a chiral carbon. A sample enriched in one enantiomer can be active; a perfectly 1:1 mixture is racemic.

A pure (+) enantiomer and pure (−) enantiomer rotate light by equal magnitudes in opposite directions. Mixing equal amounts gives zero observed rotation.

No net rotation does not prove that no chiral molecules are present; it may indicate cancellation in a racemate.

The two enantiomers of one substance rotate plane-polarised light by equal angles in opposite directions under the same conditions. One is dextrorotatory (+), the other laevorotatory (−).

The sign of rotation is measured experimentally; it is not predicted from the R/S descriptor or from the direction in which the structure is drawn on a page.

If one enantiomer rotates light +12°, its mirror image rotates it −12° at the same concentration, path length and temperature.

R/S nomenclature and +/− optical rotation are independent labels. Never replace one with the other.

A chiral drug may exist as enantiomers that have the same bulk physical properties but different biological effects because receptors, enzymes and transport proteins are chiral.

Synthetic preparation may therefore aim for one enantiomer, resolve a racemate, or test the mixture carefully. The useful enantiomer can be more active, while the other may be inactive or have a different effect.

A molecule designed to fit one enzyme binding site like a hand in a glove may have a mirror-image form that binds weakly or to another target.

“One enantiomer is always harmless” is not a chemical rule. Biological effects must be measured, and a racemate is not automatically equivalent to a pure enantiomer.