Stereochemistry, a subdiscipline ofchemistry, studies the spatial arrangement ofatoms that form the structure ofmolecules and their manipulation.[1] The study of stereochemistry focuses on the relationships betweenstereoisomers, which are defined as having the same molecular formula and sequence of bonded atoms (constitution) but differing in the geometric positioning of the atoms in space. For this reason, it is also known as3D chemistry—the prefix "stereo-" means "three-dimensionality".[2] Stereochemistry applies to all kinds of compounds and ions,organic andinorganic species alike. Stereochemistry affectsbiological,physical, andsupramolecular chemistry.
Cahn–Ingold–Prelog priority rules are part of a system for describing a molecule's stereochemistry. They rank the atoms around a stereocenter in a standard way, allowing unambiguous descriptions of their relative positions in the molecule. AFischer projection is a simplified way to depict the stereochemistry around a stereocenter.
Stereochemistry has important applications in the field of medicine, particularly pharmaceuticals. An often cited example of the importance of stereochemistry relates to the thalidomide disaster.Thalidomide is apharmaceutical drug, first prepared in 1957 in Germany, prescribed for treating morning sickness in pregnant women. The drug was discovered to beteratogenic, causing seriousgenetic damage to early embryonic growth and development, leading to limb deformation in babies. Several proposedmechanisms of teratogenicity involve different biological functions for the (R)- and (S)-thalidomide enantiomers.[3] In the human body, however, thalidomide undergoesracemization: even if only one of the two enantiomers is administered as a drug, the other enantiomer is produced as a result of metabolism.[4] Accordingly, it is incorrect to state that one stereoisomer is safe while the other is teratogenic.[5] Thalidomide is currently used for the treatment of other diseases, notably cancer andleprosy. Strict regulations and controls have been implemented to avoid its use by pregnant women and prevent developmental deformities. This disaster was a driving force behind requiring strict testing of drugs before making them available to the public.
In yet another example, the drugibuprofen can exist as (R)- and (S)-isomers. Only the (S)-ibuprofen is active in reducing inflammation and pain.[6][7]
Isomers are of two types: diastereomers (also called diastereoisomers) and enantiomers. Enantiomers are non-superimposable mirror images. Diastereomers are all other types of isomers.
Epimers are a subcategory of diastereomers that differ in absolute configuration configurations at only one corresponding stereocenter. They are commonly found insugar chemistry, where two sugars can differ by the configuration of a single carbon atom. D-glucose and D-galactose are epimers, differing only at the C-4 position in their structure. (seesugar numbering)
Atropisomerism are another kind of diasteromer. They exist because of the inability to rotate about a bond, such as due tosteric hindrance between functional groups on two sp2-hybridized carbon atoms. Usually atropisomers are chiral, and as such they are a form ofaxial chirality. Atropisomerism can be described as conformational isomerism
In 1815,Jean-Baptiste Biot's observation of optical activity marked the beginning of organic stereochemistry history. He observed that organic molecules were able to rotate the plane of polarized light in a solution or in the gaseous phase.[8] Despite Biot's discoveries,Louis Pasteur is commonly described as the first stereochemist, having observed in 1842 thatsalts oftartaric acid collected fromwine production vessels could rotate the plane ofpolarized light, but that salts from other sources did not. This was the only physical property that differed between the two types of tartrate salts, which is due tooptical isomerism. In 1874,Jacobus Henricus van 't Hoff andJoseph Le Bel explained optical activity in terms of the tetrahedral arrangement of the atoms bound to carbon. Kekulé explored tetrahedral models earlier, in 1862, but never published his work; Emanuele Paternò probably knew of these but was the first to draw and discuss three dimensional structures, such as of1,2-dibromoethane in theGiornale di Scienze Naturali ed Economiche in 1869.[9] The term "chiral" was introduced byLord Kelvin in 1904.Arthur Robertson Cushny, a Scottish Pharmacologist, first provided a clear example in 1908 of a bioactivity difference between enantiomers of a chiral molecule viz. (−)-Adrenaline is two times more potent than the (±)- form as a vasoconstrictor and in 1926 laid the foundation for chiral pharmacology/stereo-pharmacology[10][11] (biological relations of optically isomeric substances). Later in 1966, the Cahn–Ingold–Prelog nomenclature or Sequence rule was devised to assign absolute configuration tostereogenic/chiral center (R- and S- notation)[12] and extended to be applied across olefinic bonds (E- and Z- notation).
^Ernest ElielBasic Organic Stereochemistry ,2001ISBN0471374997; Bernard Testa and John CaldwellOrganic Stereochemistry: Guiding Principles and Biomedicinal Relevance2014ISBN3906390691; Hua-Jie ZhuOrganic Stereochemistry: Experimental and Computational Methods2015ISBN3527338225; László Poppe, Mihály Nógrádi, József Nagy, Gábor Hornyánszky, Zoltán BorosStereochemistry and Stereoselective Synthesis: An Introduction2016ISBN3527339019
^Nasipuri, D (2021).Stereochemistry of Organic Compounds Principles and Applications (4th ed.). New Delhi: New Age International. p. 1.ISBN978-93-89802-47-4.{{cite book}}: CS1 maint: publisher location (link)
^Cahn, R. S.; Ingold, Christopher; Prelog, V. (April 1966). "Specification of Molecular Chirality".Angewandte Chemie International Edition in English.5 (4):385–415.doi:10.1002/anie.196603851.ISSN0570-0833.
-pent-2-%25C3%25A8ne.svg)
-pent-2-%25C3%25A8ne.svg)
-1-Bromo-1%2c2-dichloroethene.svg)
-1-Bromo-1%2c2-dichloroethene.svg)
