Biochemistry - Chemical Reactions in Living Cells, Volume 1 - D. Metzler 1980

The Molecules We Are Made Of
Principles of Small Molecule Construction
Asymmetry: Right- and Left-Handed Molecules

Our left and right hands look almost identical, yet they differ from one another—one is the mirror image of the other. Practically speaking, this difference means that a right-hand glove cannot be worn on the left hand. However, while we encounter the distinction between left and right on a daily basis, putting into words exactly how the right hand differs from the left is no easy task. At the same time, because biochemical compounds—both monomers and polymers—are largely asymmetric, understanding molecular asymmetry is extremely vital. One must be able to visualize the spatial arrangement of asymmetric molecules and represent their structures on paper. To master this, it is necessary to work constantly with molecular models, or better yet, to build such models with your own hands (see Appendix).

When four different groups are attached to a central carbon atom, the molecule is invariably asymmetric. These four groups can be arranged in two ways, yielding two different configurations. Let us consider an a-amino acid

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To depict the three-dimensional Structure of a molecule on a flat surface, bonds pointing out of the plane of the drawing toward the reader are often represented as wedges, whereas bonds extending behind the plane of the drawing are shown as thin solid or dashed lines:

Amino Acids whose configuration about the a-carbon atom is the same as in the formulas above are called L-amino acids. Amino acids that are mirror images of L-Amino acids are termed D-amino acids¹. The L- and D-forms of the same compound are referred to as its enantiomorphic forms or enantiomers.

The structure of an L-amino acid was depicted above in four different ways. To show that we are dealing with the exact same structure, the molecule must be rotated in space so that the carboxyl group is at the top and the side chain (R group) is at the bottom (extending behind the plane of the drawing); meanwhile, the amino group and the hydrogen atom must end up on opposite sides of the carbon atom, projecting forward from the plane of the drawing. According to the convention proposed by E. Fischer, an amino acid is in the L-configuration if, in the aforementioned orientation, its amino group is on the left, and in the D-configuration if it is on the right.

At the same time, Fischer proposed always depicting amino acids in this specific orientation, representing all bonds with ordinary lines, as shown in the Fischer projection formula for L-Alanine below. According to the Cahn–Ingold–Prelog nomenclature (Section 5), this configuration is designated as S.

Biochemical reactions are typically highly stereospecific; an enzyme acting as a catalyst for a reaction exerts its effect only if the molecule exists in one of the two configurations. A closely related fact is that Proteins generally consist entirely of L-amino acids.

In older literature, when discussing optical isomerism manifested in the existence of D- and L-compounds, the terms "asymmetric carbon atom" or asymmetric center were used. Today, the terms chiral molecules, chiral centers, and chirality (derived from the Greek word meaning "handness") are more commonly employed. Compounds with a single chiral center form a single enantiomorphic pair, while molecules with two or more chiral centers form a family of diastereomers. Diastereomers form pairs of isomers that have opposite configurations at one or more chiral centers, but are not mirror images of one another. Examples include L-Threonine¹, which has the 2(S),3(R)-configuration, and its diastereomer, L-allothreonine, which has the 2(S),3(S)-configuration.

¹ D- and L-configurations correspond to a specific spatial arrangement of atoms in a molecule. The experimentally measurable property related to molecular asymmetry is optical rotation (Ch. 13, Sec. B.5). Sometimes, the sign of optical rotation (+ or —) is indicated alongside the name of the compound, for example, D(+)-glucose. The older designations d (dextrorotatory) and l (levorotatory) have the same meaning. However, a compound in the D-configuration may exhibit either a "+" or a "—" sign of optical rotation.