Question

Of the 19 L amino acids, 18 have the \(S\) configuration at the \(\alpha\) carbon. Cysteine is the only L. amino acid that has an \(R\) configuration. Explain.

Short answer

Cysteine's thiol group gives it an \(R\) configuration due to higher priority in the R group.

Step-by-step solution

Understand the Problem

To determine why cysteine is the only L-amino acid with an \(R\) configuration, we need to consider the structure of cysteine compared to other L-amino acids.

Review Structure & Configuration

In amino acids, the \(\alpha\) carbon is bonded to four groups: the amino group, the carboxyl group, the R group, and hydrogen. The priority of these groups determines the configuration (\(R\) or \(S\)).

Determine Priority of Groups

For most amino acids, the typical priority order (using Cahn-Ingold-Prelog rules) is: amino group > carboxyl group > R group > hydrogen. This order results in an \(S\) configuration for L-amino acids.

Special Case of Cysteine

Cysteine has a thiol group (\(-SH\)) in its R group. Sulfur has a higher atomic number than other atoms typically in the R group, thus raising the priority of the R group above the carboxyl group.

Compare Priorities to Determine Configuration

Due to the thiol group, the R group in cysteine is prioritized higher, resulting in an \(R\) configuration when applying the Cahn-Ingold-Prelog rules.

Key concepts

Cahn-Ingold-Prelog priority rules

The Cahn-Ingold-Prelog priority rules are essential in determining the configurations of chiral centers in molecules. These rules help us assign priorities to different substituents attached to a chiral center based on atomic number.

• The atom with the highest atomic number gets the highest priority.
• If two atoms have the same atomic number, proceed to the next atoms along the chain until a difference is found.
• Double and triple bonds are treated as if the bonded atoms are duplicated or triplicated.

By using these priority rules, chemists can systematically determine whether a chiral center is of the R (rectus) or S (sinister) configuration, which is critical for characterizing molecular structures.

Chiral centers in amino acids

Amino acids are organic compounds containing both an amino group and a carboxyl group, and they also have a unique R group. The \(\alpha\) carbon in amino acids is typically a chiral center, meaning it is attached to four different groups.

• This makes it a central player in determining the overall configuration of the amino acid.
• Each chiral center can have either an R or S configuration, based on the priority of the groups attached to it.

The chiral nature of amino acids is vital in biochemistry because it can influence how proteins are shaped and how they function in the body.

R and S configuration

Once priorities of the attached groups are determined using the Cahn-Ingold-Prelog rules, the configuration at the chiral center can be assigned as either \(R\) or \(S\).

• Arrange the molecule so the group with the lowest priority is pointed away from you.
• If the remaining three groups decrease in priority in a clockwise arrangement, the configuration is \(R\).
• If the order is counterclockwise, then the configuration is \(S\).

Most L-amino acids have an \(S\) configuration. However, configurations can differ due to the priority of the attached groups, which is notably different in cysteine.

Cysteine stereochemistry

Cysteine is unique among the L-amino acids because of its \(R\) configuration, despite being in the same L-series as amino acids typically classified as \(S\). This anomaly occurs because cysteine's R group contains a sulfur atom, which has a higher atomic number than oxygen, nitrogen, or carbon.

• In cysteine, the priority order becomes: thiol group (R group) > amino group > carboxyl group > hydrogen.
• The high priority of the sulfur atom in the thiol group forces the configuration to \(R\) instead of \(S\).

This inversion in priority due to the sulfur atom exemplifies the impact of atomic composition on stereochemistry in amino acids.