STEREOCHEMISTRY

Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms within molecules. An important branch of stereochemistry is the study of chiral molecules.

Stereochemistry is also known as 3D chemistry because the prefix "stereo-" means "three-dimensionality".

The study of stereochemical problems spans the entire range of organic, inorganic, biological, physical and supramolecular chemistries. Stereochemistry includes methods for determining and describing these relationships; the effect on the physical or biological properties these relationships impart upon the molecules in question, and the manner in which these relationships influence the reactivity of the molecules in question (dynamic stereochemistry).

Thalidomide example

An oft cited example of the importance of stereochemistry relates to the thalidomide disaster. thalidomide is a drug, first prepared in 1957 in germany, prescribed for treating morning sickness in pregnant women. The drug was discovered to be teratogenic, causing serious genetic damage to early embrionyc growth and development, leading to limb deformation in babies. Some of the several proposed mechanism of teratogenecity involve a different biological function for the (R)- and the (S)-thalidomide enantiomers. In the human body however, thalidomide undergoes racemization even if only one of the two enantiomers is administered as a drug, the other enantiomer is produced as a result of metabolism. Accordingly, it is incorrect to state that one of the stereoisomer is safe while the other is teratogenic. Thalidomide is currently used for the treatment of other diseases, notably cancer and leprosy. Strict regulations and controls have been enabled to avoid its use by pregnant women and prevent developmental deformations. This disaster was a driving force behind requiring strict testing of drugs before making them available to the public.

Types

ATROPISOMERISM

steric strain barrier to rotation is high enough to allow for the isolation of the conformers. The word atropisomer is derived from the Greek a, meaning not, and tropos, meaning turn. The name was coined by Kuhn in 1933, but atropisomerism was first detected in 6,6’-dinitro-2,2’-diphenic acid by Christie in 1922.

Oki defined atropisomers as conformers that interconvert with a half-life of more than 1000 seconds at a given temperature. Atropisomers are an important class of compounds because they display axial chirality. They differ from other chiral compounds in that they can be equilibrated thermally whereas in the other forms of chirality isomerization is usually only possible chemically.

The most important class of atropisomers are biaryls such as diphenic acid, which is a derivative of biphenyl with a complete set of ortho substituents. Others are dimers of naphthalene derivatives such as 1,1'-bi-2-naphthol. In a similar way, aliphatic ring systems like cyclohexanes linked through a single bond may display atropisomerism provided that bulky substituents are present.

Examples of naturally occurring atropisomers include vancomycin and knipholone, which is found in the roots of Kniphofia foliosa of the family Asphodelaceae.

Separation of atropisomers is possibly by chiral resolution methods such as selective crystallization. In an atropo-enantioselective or atropselective synthesis one atropisomer is formed at the expense of the other. Atroposelective synthesis may be carried out by use of chiral auxiliaries like a CBS catalyst in the total synthesis of knipholone or by approaches based on thermodynamic equilibration when an isomerization reaction favors one atropisomer over the other.

In organic chemistry BINAP is a ligand that is used in the preparation of optically active stereoisomers.

CIS-TRANS ISOMERISM

In organic chemistry, cis/trans isomerism (also known as geometric isomerism, configuration isomerism, or E/Z isomerism) is a form of stereoisomerism describing the orientation of functional groups within a molecule. In general, such isomers contain double bonds, which cannot rotate, but they can also arise from ring structures, wherein the rotation of bonds is greatly restricted. Cis and trans isomers occur both in organic molecules and in inorganic coordination complexes.

The terms cis and trans are from Latin, in which cis means "on the same side" and trans means "on the other side" or "across". The term "geometric isomerism" is considered an obsolete synonym of "cis/trans isomerism" by IUPAC. It is sometimes used as a synonym for general stereoisomerism (e.g., optical isomerism being called geometric isomerism); the correct term for non-optical stereoisomerism is diastereomerism.

CONFORMATIONAL ISOMERISM

In chemistry, conformational isomerism is a form of stereoisomerism in which the isomers can be interconverted exclusively by rotations about formally single bonds. Such isomers are generally referred to as conformational isomers or conformers and specifically as rotamers when the rotation leading to different conformations is restricted (hindered) rotation, in the sense that there exists a rotational energy barrier that needs to be overcome to convert one conformer to another. Conformational isomers are thus distinct from the other classes of stereoisomers for which interconversion necessarily involves breaking and reforming of chemical bonds. The rotational barrier, or barrier to rotation, is the activation energy required to interconvert rotamers.

DIASTEREOMER

Diastereomers (sometimes called diastereoisomers) are stereoisomers that are not enantiomers. Diastereomerism occurs when two or more stereoisomers of a compound have different configurations at one or more (but not all) of the equivalent (related) stereocenters and are not mirror images of each other. When two diastereoisomers differ from each other at only one stereocenter they are epimers. Each stereocenter gives rise to two different configurations and thus increases the number of stereoisomers by a factor of two.

Diastereomers differ from enantiomers in that the latter are pairs of stereoisomers that differ in all stereocenters and are therefore mirror images of one another. Enantiomers of a compound with more than one stereocenter are also diastereomers of the other stereoisomers of that compound that are not their mirror image. Diastereomers have different physical properties (unlike enantiomers) and different chemical reactivity.

Cis-trans isomerism and conformational isomerism are also forms of diastereomerism.

Diastereoselectivity is the preference for the formation of one or more than one diastereomer over the other in an organic reaction.

ENANTIOMERS

In chemistry, an enantiomer, is one of two stereoisomers that are mirror images of each other that are non-superposable (not identical), much as one's left and right hands are the same except for opposite orientation.

Organic compounds that contain an asymmetric (chiral) Carbon usually have two non-superimposable structures. These two structures are mirror images of each other and are, thus, commonly called enantiomorphs (enantio = opposite ; morph = form) Hence, optical isomerism (which occurs due to these same mirror-image properties) is now commonly referred to as enantiomerism

Enantiopure compounds refer to samples having, within the limits of detection, molecules of only one chirality.

Enantiomers have, when present in a symmetric environment, identical chemical and physical properties except for their ability to rotate plane-polarized light (+/−) by equal amounts but in opposite directions (although the polarized light can be considered an asymmetric medium). A mixture of equal parts of an optically active isomer and its enantiomer is termed racemic and has zero net rotation of plane-polarized light because the positive rotation of each (+) form is exactly counteracted by the negative rotation of a (−) one.

Enantiomers of each other often show different chemical reactions with other substances that are also enantiomers. Since many molecules in the bodies of living beings are enantiomers themselves, there is often a marked difference in the effects of two enantiomers on living beings. In drugs, for example, often only one of a drug's enantiomers is responsible for the desired physiologic effects, while the other enantiomer is less active, inactive, or sometimes even responsible for adverse effects (unwanted side-effects).

Owing to this discovery, drugs composed of only one enantiomer ("enantiopure") can be developed to enhance the pharmacological efficacy and sometimes do away with some side effects. An example of this kind of drug is eszopiclone (Lunesta), which is enantiopure and therefore is given in doses that are exactly 1/2 of the older, racemic mixture called zopiclone. In the case of eszopiclone, the S enantiomer is responsible for all the desired effects, though the other enantiomer seems to be inactive; while an individual must take 2 mg of zopiclone to get the same therapeutic benefit as they would receive from 1 mg of eszopiclone, that appears to be the only difference between the two drugs.

CONFORMATIONAL ISOMERISM

In chemistry, conformational isomerism is a form of stereoisomerism in which the isomers can be interconverted exclusively by rotations about formally single bonds. Such isomers are generally referred to as conformational isomers or conformers and specifically as rotamers when the rotation leading to different conformations is restricted (hindered) rotation, in the sense that there exists a rotational energy barrier that needs to be overcome to convert one conformer to another. Conformational isomers are thus distinct from the other classes of stereoisomers for which interconversion necessarily involves breaking and reforming of chemical bonds. The rotational barrier, or barrier to rotation, is the activation energy required to interconvert rotamers.

CHIRALITY

"L-form" redirects here. For the bacterial strains, see L-form bacteria.

Two enantiomers of a generic amino acid

(S)-Alanine (left) and (R)-alanine (right) in zwitterionic form at neutral pH

A chiral molecule /ˈkaɪərəl/ is a type of molecule that has a non-superposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom.

The term chiral in general is used to describe an object that is not superposable on its mirror image. Achiral (not chiral) objects are objects that are identical to their mirror image. Human hands are perhaps the most universally recognized example of chirality: The left hand is a non-superposable mirror image of the right hand; no matter how the two hands are oriented, it is impossible for all the major features of both hands to coincide. This difference in symmetry becomes obvious if someone attempts to shake the right hand of a person using his left hand, or if a left-handed glove is placed on a right hand. The term chirality is derived from the Greek word for hand, χειρ (kheir). It is a mathematical approach to the concept of "handedness".

In chemistry, chirality usually refers to molecules. Two mirror images of a chiral molecule are called enantiomers or optical isomers. Pairs of enantiomers are often designated as "right-" and "left-handed".

Molecular chirality is of interest because of its application to stereochemistry in inorganic chemistry, organic chemistry, physical chemistry, biochemistry, and supramolecular chemistry.