Many organic molecules exist as non-superimposable mirror images of each other, a property known as chirality. These mirror-image molecules, called enantiomers, possess identical chemical formulas but differ in the three-dimensional arrangement of their atoms. To communicate precisely about these different spatial arrangements, a classification system is necessary. The D/L system, or Fischer-Rosanoff convention, arose as an early, historical method for distinguishing between these chiral forms, particularly for biologically relevant compounds like sugars and amino acids.
Defining Relative Configuration
The D/L system is fundamentally a nomenclature of relative configuration, meaning the assignment is made by comparing a molecule’s structure to a chosen reference standard. This standard molecule is glyceraldehyde, the simplest carbohydrate with a chiral center. The two enantiomers of glyceraldehyde, designated D- and L-glyceraldehyde, serve as the basis for the entire system.
To apply this system, the molecule is drawn using a Fischer projection, a two-dimensional representation where the main carbon chain is oriented vertically. The D or L assignment is determined by the position of a specific functional group on the stereocenter farthest from the main functional group. For most sugars, this involves looking at the hydroxyl (\(\text{-OH}\)) group on the lowest-numbered chiral carbon.
If the \(\text{-OH}\) group on this determining stereocenter is drawn on the right side of the vertical chain, the molecule is assigned the D-configuration. Conversely, if the \(\text{-OH}\) group is on the left side, the molecule is assigned the L-configuration. This assignment is based on a chemical relationship to the reference glyceraldehyde, where D-sugars are chemically traceable back to D-glyceraldehyde.
D/L Notation Versus Optical Activity
A common point of confusion is the distinction between the D/L notation and the physical property of optical activity. The capital letters D and L indicate the molecule’s structural configuration relative to glyceraldehyde, not the direction in which it rotates plane-polarized light. Optical activity is an experimental observation, measured using a polarimeter, and is denoted by a plus sign (\(+\)) for dextrorotatory (rotating light to the right) or a minus sign (\(–\) ) for levorotatory (rotating light to the left).
There is no direct correlation between the D/L configuration and the direction of optical rotation. For example, D-glyceraldehyde is dextrorotatory, denoted as \(\text{D-(+)-glyceraldehyde}\). However, D-fructose is levorotatory, and is correctly named \(\text{D-(-)-fructose}\). Similarly, the naturally occurring L-amino acid L-serine is levorotatory, but many other L-amino acids commonly found in proteins are dextrorotatory.
The D/L label is a convention for describing the spatial arrangement of atoms, while the \((+)\) or \((-)\) sign describes a measurable physical property. When both are listed, such as in \(\text{D-(+)-glucose}\), the D refers to the configuration relative to glyceraldehyde, and the \((+)\) indicates the experimental observation that a solution of the compound rotates plane-polarized light to the right. The lack of a fixed relationship highlights the difference between a structural naming convention and an empirical measurement.
Biological Significance in Sugars and Amino Acids
The D/L system remains widely used within biochemistry due to a phenomenon called biological homochirality. Living systems exclusively utilize one enantiomer for most biomolecules, making the D/L designation a convenient shorthand for the biologically relevant form. This preference is particularly pronounced in the two major classes of biomolecules the system was designed to classify: sugars and amino acids.
Almost all naturally occurring carbohydrates, such as glucose and ribose, are D-isomers. This means that the \(\text{-OH}\) group on the lowest chiral carbon is on the right in the Fischer projection. In contrast, nearly all amino acids that make up proteins, with the exception of achiral glycine, are L-isomers. This uniformity is why L-amino acids and D-sugars are the standard forms in mammalian metabolism and cellular structure.
Enzymes, which are highly specific biological catalysts, are themselves chiral and have evolved to recognize and interact with only one of the two possible enantiomers. A metabolic pathway designed to process \(\text{D-glucose}\) will typically be unable to effectively process \(\text{L-glucose}\). This stereoselectivity by biological machinery is the reason the D/L notation continues to be a practical and recognized system in fields like nutrition, pharmacology, and molecular biology.
Transition to the R/S System
The D/L system is confined to molecules that are easily related to glyceraldehyde, primarily simple carbohydrates and amino acids, representing a significant limitation. It also names the entire molecule based on a single, often distant, stereocenter, which can lead to ambiguity in complex molecules with multiple chiral centers. This restriction necessitated the development of a more universal and precise method for assigning stereochemistry.
The modern standard, known as the Cahn-Ingold-Prelog (C.I.P.) system, uses the \(\text{R/S}\) nomenclature to describe absolute configuration. Unlike the D/L system’s reliance on a reference molecule, the \(\text{R/S}\) system assigns a configuration to every chiral center independently. This is achieved by using a set of priority rules based on the atomic numbers of the atoms directly attached to the chiral center.
The \(\text{R}\) (from the Latin rectus for right) and \(\text{S}\) (from the Latin sinister for left) designations provide an unambiguous description of the spatial arrangement for any chiral molecule, regardless of its class or complexity. Because the \(\text{R/S}\) system is non-comparative and universally applicable, it has largely replaced the D/L system in general organic chemistry and chemical synthesis. However, the \(\text{D/L}\) system persists in biochemistry as a convenient, historical shorthand.