racemization

Racemization is the process by which a chiral center in a molecule is converted into its mirror image, or when a chiral molecule interconverts with its enantiomer, resulting in a racemic mixture containing equal amounts of both enantiomers. This phenomenon can occur at stereogenic carbon atoms or at axes in atropisomeric compounds.

Racemization can proceed through mechanisms that generate achiral or planar intermediates, such as enolates, carbocations, iminium ions, or carbanions, enabling interchange of configuration. Acid- or base-catalyzed conditions, heat, or catalytic metals can accelerate the process. In carbonyl chemistry, enolization is a common route; in amino acids, alpha-carbon deprotonation/reprotonation leads to D/L interconversion; in carbohydrates and other substrates, similar pathways exist.

Racemization is relevant to chemistry and pharmacology. In pharmaceuticals, it can alter potency, pharmacokinetics, and safety; many drugs are marketed as racemates or as single enantiomers, with regulatory emphasis on enantiomeric purity. Racialization can also occur in biological systems over time, and certain amino acid residues, such as aspartic acid, can racemize in aging proteins, contributing to protein modification.

Detection and measurement of racemization rely on chiral analytical techniques. Chiral high-performance liquid chromatography, polarimetry, and NMR with chiral shift reagents quantify enantiomeric excess and track racemization kinetics.

Prevention and control of racemization involve adjusting storage and processing conditions to minimize exposure to acid or base catalysis, high temperatures, or moisture. Strategies include controlled pH, reduced temperature, anhydrous environments, protective groups, and formulation choices that stabilize the desired enantiomer.