Question

A matter of convention. All Lamino acids have an \(S\) absolute configuration except L-cysteine, which has the \(R\) configuration. Explain why L-cysteine is designated as having the \(R\) absolute configuration.

Short answer

L-cysteine's sulfur gives it a high priority, causing a clockwise trace, resulting in an "R" configuration.

Step-by-step solution

Understand the Absolute Configuration System

The absolute configuration of a chiral molecule is determined using the Cahn-Ingold-Prelog (CIP) priority rules. These rules rank substituents around a chiral center based on atomic number, isotopic mass, and connectivity.

Analyze L-Cysteine's Chiral Center

L-cysteine has a sulfur atom (which has a higher atomic number than the oxygen or nitrogen) in its side chain, bonded to the chiral center carbon alongside hydrogen, carboxyl, and amino groups.

Assign Priority to Substituents

According to CIP rules, the sulfur atom in the thiol group (-SH) of L-cysteine is given the highest priority (1), followed by the carboxyl group (2), the amino group (3), and the hydrogen atom (4).

Use the Priority to Determine Configuration

With the lowest priority group (hydrogen) oriented away from us, trace a path from priority 1 to 2 to 3. For L-cysteine, the trace is clockwise, which corresponds to the "R" (rectus, Latin for "right") configuration.

Key concepts

Chiral Center

A chiral center is a fundamental concept in stereochemistry, specifically dealing with the spatial arrangement of atoms around a specific atom in a molecule, creating non-superimposable mirror images. This chiral center, often a carbon atom, is bonded to four different substituents, leading to these unique configurations. Such configurations cause the molecule to rotate plane-polarized light, a characteristic of chirality that makes these molecules critical in fields like pharmacology and biochemistry.

• The central carbon atom is the focus in compounds such as amino acids.
• The different groups attached to this center must be considered for determining molecular properties.

Identifying the chiral center helps in understanding why certain molecules exhibit optical activity and allows for further analysis of their stereochemistry.

Cahn-Ingold-Prelog Priority Rules

The Cahn-Ingold-Prelog (CIP) priority rules are used to unequivocally name the absolute configuration of stereo centers in molecules. These rules are crucial for identifying the sequence in which atoms attached to a chiral center are prioritized.

• Priority is assigned based on atomic number: the higher the atomic number of the atoms directly attached to the chiral center, the higher the priority.
• In cases where atomic numbers are identical, one looks to the next set of atoms up the chain to break ties.
• Heavy isotopes take precedence over lighter ones.

In the context of L-cysteine, these rules determine that the sulfur atom has the highest priority due to its high atomic number compared to other substituents like oxygen and nitrogen. This precise and systematic method ensures that the configuration is determined accurately irrespective of the visual orientation of the molecule.

L-Cysteine Configuration

L-cysteine is an exception to the rule that most L-amino acids have an "S" (sinister, Latin for "left") configuration. The unique structure of L-cysteine results in an "R" (rectus, Latin for "right") configuration due to its substituents and how they are prioritized under the Cahn-Ingold-Prelog (CIP) rules.

• The sulfur in the thiol (-SH) group is key to this configuration, given its higher ranking among the groups attached to the chiral center.
• By orienting the molecule so that the lowest priority group (hydrogen) is at the back, tracing a path from the highest to the third highest priority group forms a clockwise path, revealing the "R" configuration.

This orientation and the path determined by the CIP rules provide clarity on why L-cysteine stands out, highlighting its configuration without ambiguity.