Inchemistry,isomers aremolecules orpolyatomic ions with identicalmolecular formula – that is, the same number ofatoms of eachelement – but distinct arrangements of atoms in space.[1]Isomerism refers to the existence or possibility of isomers.
Isomers do not necessarily share similarchemical orphysical properties. Two main forms of isomerism arestructural (or constitutional) isomerism, in whichbonds between the atoms differ; andstereoisomerism (or spatial isomerism), in which the bonds are the same but therelative positions of the atoms differ.
Isomeric relationships form ahierarchy. Two chemicals might be the same constitutional isomer, but upon deeper analysis be stereoisomers of each other. Two molecules that are the same stereoisomer as each other might be in different conformational forms or be differentisotopologues. The depth of analysis depends on the field of study or the chemical and physical properties of interest.
The English word "isomer" (/ˈaɪsəmər/) is aback-formation from "isomeric",[2] which was borrowed throughGermanisomerisch[3] fromSwedishisomerisk; which in turn was coined fromGreek ἰσόμερoςisómeros, with rootsisos = "equal",méros = "part".[4]
Structural isomers have the same number of atoms of each element (hence the samemolecular formula), but the atoms are connected in distinct ways.[5]
For example, there are three distinct compounds with the molecular formula:
The first two isomers shown of arepropanols, that is,alcohols derived frompropane. Both have a chain of three carbon atoms connected by single bonds, with the remaining carbonvalences being filled by sevenhydrogen atoms and by ahydroxyl group comprising theoxygen atom bound to a hydrogen atom. These two isomers differ on which carbon the hydroxyl is bound to: either to an extremity of the carbon chainpropan-1-ol (1-propanol,n-propyl alcohol,n-propanol;I) or to the middle carbonpropan-2-ol (2-propanol, isopropyl alcohol, isopropanol;II). These can be described by thecondensed structural formulas and.
The third isomer of is theethermethoxyethane (ethyl-methyl-ether;III). Unlike the other two, it has the oxygen atom connected to two carbons, and all eight hydrogens bonded directly to carbons. It can be described by the condensed formula.
The alcohol "3-propanol" is not another isomer, since the difference between it and 1-propanol is not real; it is only the result of an arbitrary choice in the direction of numbering the carbons along the chain. For the same reason, "ethoxymethane" is the same molecule as methoxyethane, not another isomer.
1-Propanol and 2-propanol are examples ofpositional isomers, which differ by the position at which certain features, such asdouble bonds orfunctional groups, occur on a "parent" molecule (propane, in that case).
There are also three structural isomers of thehydrocarbon:
 |  |  |
| I Propadiene | II Propyne | III Cyclopropene |
In two of the isomers, the three carbon atoms are connected in an open chain, but in one of them (propadiene or allene;I) the carbons are connected by twodouble bonds, while in the other (propyne or methylacetylene;II) they are connected by a single bond and atriple bond. In the third isomer (cyclopropene;III) the three carbons are connected into a ring by two single bonds and a double bond. In all three, the remaining valences of the carbon atoms are satisfied by the four hydrogens.
Again, note that there is only one structural isomer with a triple bond, because the other possible placement of that bond is just drawing the three carbons in a different order. For the same reason, there is only one cyclopropene, not three.
Tautomers are structural isomers which readily interconvert, so that two or more species co-exist in equilibrium such as
.[6]
Important examples areketo-enol tautomerism and the equilibrium between neutral andzwitterionic forms of anamino acid.
Stereoisomers have the same atoms or isotopes connected by bonds of the same type, but differ in the relative positions of those atoms in space. Two broad types of stereoisomers exist, enantiomers and diastereomers. Enantiomers have identical physical properties but diastereomers do not.[7]
Two compounds are said to beenantiomers if their molecules are mirror images of each other and cannot be made to coincide only by rotations or translations – like a left hand and a right hand. The two shapes are said to bechiral.
A classic example isbromochlorofluoromethane (). The two enantiomers can be distinguished, for example, by whether the path turns clockwise or counterclockwise as seen from the hydrogen atom. In order to change one conformation to the other, at some point those four atoms would have to lie on the same plane – which would require severely straining or breaking their bonds to the carbon atom. The corresponding energy barrier between the two conformations is so high that there is practically no conversion between them at room temperature, and they can be regarded as different configurations.
The compoundchlorofluoromethane, in contrast, is not chiral; the mirror image of its molecule is also obtained by a half-turn about a suitable axis.
Another example of a chiral compound is2,3-pentadiene, a hydrocarbon that contains two overlapping double bonds. The double bonds are such that the three middle carbons are in a straight line, while the first three and last three lie on perpendicular planes. The molecule and its mirror image are not superimposable, even though the molecule has an axis of symmetry. The two enantiomers can be distinguished, for example, by theright-hand rule. This type of isomerism is calledaxial isomerism.
Enantiomers behave identically in chemical reactions, except when reacting with chiral compounds or in the presence of chiralcatalysts, such as mostenzymes. For this latter reason, the two enantiomers of most chiral compounds usually have markedly different effects and roles in living organisms. Inbiochemistry andfood science, the two enantiomers of a chiral molecule – such asglucose – are usually identified and treated as very different substances.
Each enantiomer of a chiral compound typically rotates the plane ofpolarized light that passes through it. The rotation has the same magnitude but opposite senses for the two isomers, and can be a useful way of distinguishing and measuring their concentration in a solution. For this reason, enantiomers were formerly called "optical isomers".[8][9] However, this term is ambiguous and is discouraged by theIUPAC.[10][11]
Some enantiomer pairs (such as those oftrans-cyclooctene) can be interconverted by internal motions that change bond lengths and angles only slightly. Other pairs (such as CHFClBr) cannot be interconverted without breaking bonds, and therefore are different configurations.
Stereoisomers that are not enantiomers are calleddiastereomers. Some diastereomers may containchiral centers, and some may not.[12]
A double bond between two carbon atoms forces the remaining four bonds (if they are single) to lie on the same plane, perpendicular to the plane of the bond as defined by itsπ orbital. If the two bonds on each carbon connect to different atoms, two distinct conformations are possible that differ from each other by a twist of 180 degrees of one of the carbons about the double bond.
The classical example is dichloroethene, specifically the structural isomer that has one chlorine bonded to each carbon. It has two conformational isomers, with the two chlorines on the same side or on opposite sides of the double bond's plane. They are traditionally calledcis (from Latin meaning "on this side of") andtrans ("on the other side of"), respectively, orZ andE in theIUPAC recommended nomenclature. Conversion between these two forms usually requires temporarily breaking bonds (or turning the double bond into a single bond), so the two are considered different configurations of the molecule.
More generally,cis–trans isomerism (formerly called "geometric isomerism") occurs in molecules where the relative orientation of two distinguishable functional groups is restricted by a somewhat rigid framework of other atoms.[13]
For example, in the cyclic alcoholinositol (a six-fold alcohol of cyclohexane), the six-carbon cyclic backbone largely prevents the hydroxyl and the hydrogen on each carbon from switching places. Therefore, one has different configurational isomers depending on whether each hydroxyl is on "this side" or "the other side" of the ring's mean plane. Discounting isomers that are equivalent under rotations, there are nine isomers that differ by this criterion, and behave as different stable substances (two of them being enantiomers of each other). The most common one in nature (myo-inositol) has the hydroxyls on carbons 1, 2, 3 and 5 on the same side of that plane, and can therefore be calledcis-1,2,3,5-trans-4,6-cyclohexanehexol. And each of thesecis-trans isomers can possibly have stable "chair" or "boat" conformations (although the barriers between these are significantly lower than those between differentcis-trans isomers).
Cis andtrans isomers also occur in inorganiccoordination compounds, such assquare planar complexes andoctahedral complexes.
For more complex organic molecules, thecis andtrans labels can be ambiguous. In such cases, a more precise labeling scheme is employed based on theCahn-Ingold-Prelog priority rules.[14][12]
Different isotopes of the same element can be considered as different kinds of atoms when enumerating isomers of a molecule or ion. The replacement of one or more atoms by their isotopes can create multiple structural isomers and/or stereoisomers from a single isomer.
For example, replacing two atoms of commonhydrogen () bydeuterium (, or) on anethane molecule yields two distinct structural isomers, depending on whether the substitutions are both on the same carbon (1,1-dideuteroethane,) or one on each carbon (1,2-dideuteroethane,); as if the substituent waschlorine instead of deuterium. The two molecules do not interconvert easily and have different properties, such as theirmicrowave spectrum.[15]
Another example would be substituting one atom of deuterium for one of the hydrogens inchlorofluoromethane (). While the original molecule is not chiral and has a single isomer, the substitution creates a pair of chiral enantiomers of, which could be distinguished (at least in theory) by their optical activity.[16]
When two isomers would be identical if all isotopes of each element were replaced by a single isotope, they are described asisotopomers or isotopic isomers.[17] In the above two examples if all were replaced by, the two dideuteroethanes would both become ethane and the two deuterochlorofluoromethanes would both become.
The concept of isotopomers is different fromisotopologs or isotopic homologs, which differ in their isotopic composition.[17] For example, and are isotopologues and not isotopomers, and are therefore not isomers of each other.
Another type of isomerism based on nuclear properties isspin isomerism, where molecules differ only in the relativespin magnetic quantum numbers ms of the constituent atomic nuclei. This phenomenon is significant for molecular hydrogen, which can be partially separated into two long-lived states described as spin isomers[18] or nuclear spin isomers:[19] parahydrogen, with the spins of the two nuclei pointing in opposite directions, and orthohydrogen, where the spins point in the same direction.
Isomers having distinct biological properties are common; for example, the placement ofmethyl groups. In substitutedxanthines,theobromine, found in chocolate, is avasodilator with some effects in common withcaffeine; but, if one of the two methyl groups is moved to a different position on the two-ring core, the isomer istheophylline, which has a variety of effects, includingbronchodilation andanti-inflammatory action. Another example of this occurs in thephenethylamine-based stimulant drugs.Phentermine is anon-chiral compound with a weaker effect than that ofamphetamine. It is used as an appetite-reducing medication and has mild or no stimulant properties. However, an alternate atomic arrangement givesdextromethamphetamine, which is a stronger stimulant than amphetamine.
Inmedicinal chemistry and biochemistry,enantiomers are a special concern because they may possess distinctbiological activity. Many preparative procedures afford a mixture of equal amounts of both enantiomeric forms. In some cases, the enantiomers are separated bychromatography using chiral stationary phases. They may also be separated through the formation ofdiastereomeric salts. In other cases,enantioselective synthesis have been developed.
As an inorganic example,cisplatin (see structure above) is an important drug used in cancer chemotherapy, whereas the trans isomer (transplatin) has no useful pharmacological activity.
Isomerism was first observed in 1827, whenFriedrich Wöhler preparedsilver cyanate and discovered that, although its elemental composition of was identical tosilver fulminate (prepared byJustus von Liebig the previous year),[20] its properties were distinct. This finding challenged the prevailing chemical understanding of the time, which held thatchemical compounds could be distinct only when their elemental compositions differ. (We now know that the bonding structures offulminate andcyanate can be approximately described as≡ and, respectively.)
Additional examples were found in succeeding years, such as Wöhler's 1828 discovery thaturea has the same atomic composition () as the chemically distinctammonium cyanate. (Their structures are now known to be and, respectively.) In 1830Jöns Jacob Berzelius introduced the termisomerism to describe the phenomenon.[4][21][22][23]
In 1848,Louis Pasteur observed thattartaric acid crystals came into two kinds of shapes that were mirror images of each other. Separating the crystals by hand, he obtained two version of tartaric acid, each of which would crystallize in only one of the two shapes, and rotated the plane of polarized light to the same degree but in opposite directions.[24][25] In 1860, Pasteur explicitly hypothesized that the molecules of isomers might have the same composition but different arrangements of their atoms.[26]
