In
stereochemistry
Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereois ...
, topicity is the stereochemical relationship between
substituents
A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and ''functional group'', as well as ''side ...
and the structure to which they are attached. Depending on the relationship, such groups can be ''heterotopic'', ''homotopic'', ''enantiotopic'', or ''diastereotopic''.
Homotopic
Homotopic groups in a chemical compound are equivalent groups. Two groups A and B are homotopic if the molecule remains the same (including stereochemically) when the groups are interchanged with some other atom (such as bromine) while the remaining parts of the molecule stay fixed. Homotopic atoms are always identical, in any environment. Homotopic NMR-active nuclei have the same
chemical shift
In nuclear magnetic resonance (NMR) spectroscopy, the chemical shift is the resonant frequency of an atomic nucleus relative to a standard in a magnetic field. Often the position and number of chemical shifts are diagnostic of the structure of ...
in an
NMR
Nuclear magnetic resonance (NMR) is a physical phenomenon in which nuclei in a strong constant magnetic field are perturbed by a weak oscillating magnetic field (in the near field) and respond by producing an electromagnetic signal with ...
spectrum. For example, the four hydrogen atoms of
methane
Methane ( , ) is a chemical compound with the chemical formula (one carbon atom bonded to four hydrogen atoms). It is a group-14 hydride, the simplest alkane, and the main constituent of natural gas. The relative abundance of methane on Eart ...
(CH
4) are homotopic with one another, as are the two hydrogens or the two chlorines in
dichloromethane
Dichloromethane (DCM or methylene chloride, methylene bichloride) is an organochlorine compound with the formula . This colorless, volatile liquid with a chloroform-like, sweet odour is widely used as a solvent. Although it is not miscible with ...
(CH
2Cl
2).
Enantiotopic
The
stereochemical
Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereois ...
term enantiotopic refers to the relationship between two groups in a molecule which, if one or the other were replaced, would generate a
chiral
Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object.
An object or a system is ''chiral'' if it is distinguishable from ...
compound. The two possible compounds resulting from that replacement would be
enantiomer
In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...
s.
For example, the two hydrogen atoms attached to the second carbon in
butane
Butane () or ''n''-butane is an alkane with the formula C4H10. Butane is a gas at room temperature and atmospheric pressure. Butane is a highly flammable, colorless, easily liquefied gas that quickly vaporizes at room temperature. The name but ...
are enantiotopic. Replacement of one hydrogen atom (colored blue) with a bromine atom will produce (''R'')-2-bromobutane. Replacement of the other hydrogen atom (colored red) with a bromine atom will produce the enantiomer (''S'')-2-bromobutane.
Enantiotopic groups are identical and indistinguishable except in chiral environments. For instance, the CH
2 hydrogens in
ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...
(CH
3CH
2OH) are normally enantiotopic, but can be made different (
diastereotopic) if combined with a chiral center, for instance by conversion to an
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...
of a chiral
carboxylic acid
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
such as
lactic acid
Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as natu ...
, or if coordinated to a chiral metal center, or if associated with an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
active site
In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...
, since enzymes are constituted of chiral
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s. Indeed, in the presence of the enzyme
LADH, one specific hydrogen is removed from the CH
2 group during the oxidation of ethanol to
acetaldehyde
Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is a colorless liquid or gas, boiling near room temperature. It is one of the mos ...
, and it gets replaced in the same place during the reverse reaction. The chiral environment needs not be optically pure for this effect.
Enantiotopic groups are mirror images of each other about an internal plane of symmetry. A chiral environment removes that symmetry. Enantiotopic pairs of NMR-active nuclei are also indistinguishable by NMR and produce a single signal.
Enantiotopic groups need not be attached to the same atom. For example, two hydrogen atoms adjacent to the carbonyl group in ''cis''-2,6-dimethylcyclohexanone are enantiotopic; they are related by an internal plane of symmetry passing through the carbonyl group, but deprotonation on one side of the carbonyl group or on the other will generate compounds that are enantiomers. Similarly, the replacement of one or the other with
deuterium
Deuterium (or hydrogen-2, symbol or deuterium, also known as heavy hydrogen) is one of two Stable isotope ratio, stable isotopes of hydrogen (the other being Hydrogen atom, protium, or hydrogen-1). The atomic nucleus, nucleus of a deuterium ato ...
will generate enantiomers.
Diastereotopic
The
stereochemical
Stereochemistry, a subdiscipline of chemistry, involves the study of the relative spatial arrangement of atoms that form the structure of molecules and their manipulation. The study of stereochemistry focuses on the relationships between stereois ...
term diastereotopic refers to the relationship between two groups in a molecule which, if replaced, would generate compounds that are
diastereomer
In stereochemistry, diastereomers (sometimes called diastereoisomers) are a type of stereoisomer. Diastereomers are defined as non-mirror image, non-identical stereoisomers. Hence, they occur when two or more stereoisomers of a compound have di ...
s. Diastereotopic groups are often, but not always, identical groups attached to the same atom in a molecule containing at least one chiral center.
For example, the two hydrogen atoms of the CH
2 moiety in (''S'')-2-bromobutane are diastereotopic. Replacement of one hydrogen atom (colored blue) with a bromine atom will produce (''2S,3R'')-2,3-dibromobutane. Replacement of the other hydrogen atom (colored red) with a bromine atom will produce the diastereomer (''2S,3S'')-2,3-dibromobutane.
In chiral molecules containing diastereotopic groups, such as in 2-bromobutane, there is no requirement for enantiomeric or
optical purity
In stereochemistry, enantiomeric excess (ee) is a measurement of purity used for chiral substances. It reflects the degree to which a sample contains one enantiomer in greater amounts than the other. A racemic mixture has an ee of 0%, while a si ...
; no matter its proportion, each enantiomer will generate enantiomeric sets of diastereomers upon substitution of diastereotopic groups (though, as in the case of substitution by bromine in 2-bromobutane,
meso isomers have, strictly speaking, no enantiomer).
Diastereotopic groups are not mirror images of one another about any plane. They are always different, in any environment, but may not be distinguishable. For instance, both pairs of CH
2 hydrogens in ethyl phenylalaninate hydrochloride (PhCH
2CH(NH
3+)COOCH
2CH
3 Cl
−) are diastereotopic and both give pairs of distinct
1H-NMR signals in DMSO-d
6 at 300 MHz, but in the similar ethyl 2-nitrobutanoate (CH
3CH
2CH(NO
2)COOCH
2CH
3), only the CH
2 group next to the chiral center gives distinct signals from its two hydrogens with the same instrument in CDCl
3. Such signals are often complex because of small differences in chemical shift, overlap and an additional strong coupling between
geminal
In chemistry, the descriptor geminal () refers to the relationship between two atoms or functional groups that are attached to the same atom. A geminal diol, for example, is a diol (a molecule that has two alcohol functional groups) attached t ...
hydrogens. On the other hand, the two CH
3 groups of ipsenol, which are three bonds away from the chiral center, give separate
1H doublets at 300 MHz and separate
13C-NMR signals in CDCl
3, but the diastereotopic hydrogens in ethyl alaninate hydrochloride (CH
3CH(NH
3+)COOCH
2CH
3 Cl
−), also three bonds away from the chiral center, show barely distinguishable
1H-NMR signals in DMSO-d
6.
Diastereotopic groups also arise in achiral molecules. For instance, any one pair of CH
2 hydrogens in 3-pentanol (Figure 1) are diastereotopic, as the two CH
2 carbons are
enantiotopic In stereochemistry, topicity is the stereochemical relationship between substituents and the structure to which they are attached. Depending on the relationship, such groups can be ''heterotopic'', ''homotopic'', ''enantiotopic'', or ''diastereotop ...
. Substitution of any one of the four CH
2 hydrogens creates two chiral centers at once, and the two possible hydrogen substitution products at any one CH
2 carbon will be diastereomers. This kind of relationship is often easier to detect in cyclic molecules. For instance, any pair of CH
2 hydrogens in cyclopentanol (Figure 2) are similarly diastereotopic, and this is easily discerned as one of the hydrogens in the pair will be ''cis'' to the OH group (on the same side of the ring face) while the other will be ''trans'' to it (on the opposite side).
The term diastereotopic is also applied to identical groups attached to the same end of an alkene moiety which, if replaced, would generate
geometric isomers
Geometry (; ) is, with arithmetic, one of the oldest branches of mathematics. It is concerned with properties of space such as the distance, shape, size, and relative position of figures. A mathematician who works in the field of geometry is ...
(also falling in the category of diastereomers). Thus, the CH
2 hydrogens of
propene
Propylene, also known as propene, is an unsaturated organic compound with the chemical formula CH3CH=CH2. It has one double bond, and is the second simplest member of the alkene class of hydrocarbons. It is a colorless gas with a faint petro ...
are diastereotopic, one being ''cis'' to the CH
3 group, and the other being ''trans'' to it, and replacement of one or the other with CH
3 would generate ''cis-'' or ''trans-''-2-
butene
Butene, also known as butylene, is an alkene with the formula . The word ''butene'' may refer to any of the individual compounds. They are colourless gases that are present in crude oil as a minor constituent in quantities that are too small for ...
.
Diastereotopicity is not limited to organic molecules, nor to groups attached to carbon, nor to molecules with chiral tetrahedral (''sp''
3-hybridized) centers: for instance, the pair of hydrogens in any CH
2 or NH
2 group in ''tris''(ethylenediamine)chromium(III) ion (Cr(en)
33+), where the metal center is chiral, are diastereotopic (Figure 2).
The terms enantiotopic and diastereotopic can also be applied to the faces of planar groups (especially carbonyl groups and alkene moieties). See
Cahn-Ingold-Prelog priority rule.
Heterotopic
Heterotopic groups are those that when substituted are structurally different. They are neither diastereotopic or enantiotopic nor homotopic.
See also
*
Prochiral
In stereochemistry, prochiral molecules are those that can be converted from achiral to chiral in a single step. An achiral species which can be converted to a chiral in two steps is called proprochiral.
If two identical substituents are attach ...
*
conformational analysis
In chemistry, conformational isomerism is a form of stereoisomerism in which the isomers can be interconverted just by rotations about formally single bonds (refer to figure on single bond rotation). While any two arrangements of atoms in a mo ...
References
{{Reflist
Stereochemistry
Nuclear magnetic resonance