Optical Activity and Biological Effect

Compounds with an asymmetric or chiral center give rise to enantiomers. Two isomeric forms are given that relate to each other like an image and a mirror image. They cannot be transferred to each other without breaking and reforming chemical bonds. Enantiomers share the same properties as long as they are in a nonchiral environment. When exposed to the asymmetric environment such as a protein binding pocket, they experience different interactions and thus produce different biological effects. Chiral centers are most commonly found on atoms carrying four different substituents. However, an overall handed scaffold can also give rise to chirality. When n independent stereocenters are present, 2n isomers (diastereomers) are produced, which give rise to 2n-1 racemic mixtures (pairs of equal enantiomers) as long as there is no internal inversion, mirror, or improper rotational symmetry. According to the Cahn-Ingold-Prelog priority rules chiral centers are assigned. The rules define a unique order of the attached substituents according to their atomic numbers. The substituent with the lowest priority must be rear-facing, and the direction of the remaining substituents determines R/S in order of decreasing priority. Enantiomers can be separated by fractional crystallization after conversion to diastereomeric salts with appropriate chiral auxiliaries. Enzymes such as lipases, esterases or proteases can also be used for resolution because they convert one enantiomer faster than the other for steric and kinetic reasons. Most natural products are optically active and exist in only one form. Biologically active enantiomers are called eutomers, inactive ones distomers. The biological activities of enantiomers and diastereomers can vary greatly in both strength and quality. The use of racemates must be carefully considered on a case-by-case basis. Side effects, chemical stability and different metabolism can have a decisive influence on the activity profile. At the molecular level, affinity discrimination of enantiomers is explained by different binding modes in the per se chiral binding pocket of the target protein, resulting in differences in the observed interaction pattern or strain of the adopted bound conformation. https://sn.pub/815bp7