Why is the absolute configuration R in some molecules and S in others?

The absolute configuration (R or S) of a molecule depends on the spatial arrangement of atoms around a chiral centre.

The absolute configuration of a molecule is determined by the Cahn-Ingold-Prelog (CIP) priority rules. These rules are used to assign a unique descriptor (R or S) to a chiral centre, which is a carbon atom bonded to four different groups. The descriptor R (from the Latin rectus, meaning right) or S (from the Latin sinister, meaning left) refers to the direction of rotation of the plane of polarised light by the molecule.

The CIP rules involve assigning priorities to the atoms directly attached to the chiral centre, based on their atomic numbers. The atom with the highest atomic number gets the highest priority (1), and the one with the lowest atomic number gets the lowest priority (4). If two atoms have the same atomic number, the priority is determined by the next atoms along the chain.

Once the priorities have been assigned, the molecule is oriented so that the group with the lowest priority is pointed away from the observer. If the remaining three groups decrease in priority in a clockwise direction, the configuration is R. If they decrease in priority in an anticlockwise direction, the configuration is S.

It's important to note that the absolute configuration (R or S) of a molecule is not related to its optical activity (whether it rotates plane-polarised light to the right (+) or to the left (-)). A molecule with an R configuration can be either dextrorotatory (+) or levorotatory (-), and the same applies to a molecule with an S configuration. The relationship between the absolute configuration and the direction of rotation of plane-polarised light is determined experimentally for each molecule.

In summary, the absolute configuration (R or S) of a molecule is determined by the spatial arrangement of atoms around a chiral centre, according to the Cahn-Ingold-Prelog priority rules. This configuration is a fundamental property of the molecule and is crucial for its chemical behaviour and biological activity.