Isomerism
Isomerism (from the ancient Greek word formation elements ἴσος (isos) "equal", μέρος (meros) "proportion, part, piece") is the occurrence of two or more chemical compounds with the same molecular formula and molecular mass , which are however in the link or the the spatial arrangement of the atoms. The corresponding compounds are called isomers and can be represented by different structural formulas. They differ in their chemical and / or physical and often also in their biochemical properties. Isomerism occurs primarily with organic compounds , but also with (inorganic) coordination compounds . The isomerism is divided into different areas.
Constitutional isomerism or structural isomerism
Constitutional isomers (also called structural isomers) have the same general empirical formula , but differ in the order of the atoms and in their bonds. The isomers are therefore generally different substances with different chemical (including reactivity) and physical properties (including melting and boiling point, solubility). A distinction can be made between several cases:
- Functional isomers have different functional groups , e.g. B. Ethanol (CH 3 -CH 2 -OH) and dimethyl ether CH 3 -O-CH 3 .
- Skeletal isomers have differently branched carbon backbones. They are often grouped into groups of substances. In the case of hydrocarbons, these are e.g. B. the pentanes or the hexanes . The same applies to compounds with a functional group. Thus include butanol and 2-methyl-1-propanol to the butanols .
- In positional isomers (also called local isomers or regioisomers), the same functional group is in different positions, e.g. B. with 1,2- propanediol and 1,3- propanediol .
- Bond isomers (also valence isomers ) differ in the number and / or position of σ and π bonds , e.g. B. with C 3 H 4 as propadiene or propyne .
A special case of bond isomerism is tautomerism , in which (usually two) different isomers merge into one another in a reversible chemical reaction, as parts of the molecule (mostly hydrogen atoms) change their place and thereby shift bonds, e.g. B. a previous double bond becomes a single bond and a double bond or a ring closure occurs elsewhere on the molecule. Due to the rapid achievement of chemical equilibrium, however, the individual tautomers can usually not be isolated separately.
Stereoisomerism
Stereoisomers basically have the same structure (constitution) - and thus also the same empirical formula - but differ in the spatial arrangement ( configuration ) of the atoms.
Configuration isomerism
Configuration isomers are stereoisomers, but without taking the conformation into account .
Enantiomerism
An important case are enantiomers , configurational isomers, which relate to one another like image and mirror image, but do not have a plane of symmetry within the molecule. Enantiomers therefore differ in all stereocenters (atoms which, due to four different substituents , allow two different orders among these). Important examples are sugars , amino acids, and many chiral drugs .
Diastereomerism
All configuration isomers that are not enantiomers are called diastereomers . Diastereoisomers are divided as follows:
- One form is the cis - trans isomerism , which occurs on unsymmetrically substituted double bonds or on ring systems. This isomerism is e.g. B. between maleic acid ( cis form) and fumaric acid ( trans form).
- As epimers are called pairs of diastereoisomers of a molecule with multiple stereocenters, which differ in one of these centers (such as isoleucine and Alloisoleucine -. See chart - or glucose and galactose ), but are the same in the other. Epimers are therefore always also diastereomers, but not vice versa.
- In sugar chemistry, the term anomer is used as a special case of an epimer, the difference between which lies in the first carbon (relevant when the α- or β-form of a sugar such as glucose is formed ).
- A meso shape has several centers of chirality, but also a plane of symmetry and can therefore be made to coincide with the mirror image. Generally valid is the formulation that a meso form has equivalent chiral centers (substituted with the same radicals) with opposite configuration [e.g. B. a stereocenter with ( R ) - and an identically substituted with ( S ) -configuration]. Contrary to the first appearance, two meso forms are therefore not enantiomers and are optically inactive (optical rotation value α = 0 degrees). The number of stereocenters in meso compounds is an even number (2, 4, 6, 8, etc.).
- a special form of diastereomerism is endo-exo isomerism , which only occurs with substituted bridged bicyclic hydrocarbons .
Calculation of the maximum number of stereoisomers of a molecule: 2 n with n chiral centers . If meso forms are present, the number of isomers is reduced by one per meso form.
Example: Cyclohexane with a different substituent on each of the six carbon atoms of the ring has six stereocenters, so there are a maximum of 2 6 = 64 stereoisomers.
Optical activity often occurs in connection with stereoisomers ; i.e., enantiomers rotate the plane of linearly polarized light by the same amount in opposite directions.
Conformational isomerism
All the configuration isomers mentioned so far have in common that an isomer can only be converted into another form by breaking a bond. This does not apply to the last group of isomers: Conformational isomers ( conformers ) are stereoisomers that can be converted into one another by simply rotating single bonds. Therefore, rotamers are often used . The thermal energy at room temperature is usually sufficient for the transfer. An example is the ecliptic (hidden) and staggered ethane (clearly visible in the Newman projection ). The two groups of ethane can in principle be at any angle to one another, the energy difference being less than the thermal energy, so that in a solution the isomeric forms continuously merge and cannot normally be isolated. A special case is atropisomerism , in which axial chirality occurs.
More terms
Despite the linguistic similarity, the term mesomerism does not belong in this subject area.
Forms of isomerism
The following table gives a brief overview of the most important forms of isomerism:
| Isomers | Similarities | differences | Different chemical and physical properties | Transfer possible without breaking the bond | ||
|---|---|---|---|---|---|---|
| Constitutional isomers | Molecular formula | structure | Yes | No | ||
| Stereoisomers | Configurational isomers | Diastereomers | Molecular formula + structure |
spatial arrangement | Yes | No |
| Enantiomers | spatial arrangement, but like image and mirror image | optically active, chemical differences only in the case of chiral reaction partners (e.g. enzymes ) | No | |||
| Conformational isomers | spatial position | No | Yes | |||
Isomerism of complex compounds
In complex chemistry there are a number of very different forms of isomerism, but all forms can be divided into two large groups, the constitutional isomers and the stereoisomers.
Constitutional isomerism of complex compounds
- Binding isomerism
Bond isomerism occurs when a ligand can be connected to the central atom via several different of its atoms. This is how nitro complexes or nitrite complexes differ:
The same applies to cyanates (–OCN) and isocyanates (–NCO) as well as to thiocyanates (–SCN) and isothiocyanates (–NCS).
- Ionization isomerism
In complexes, by exchanging a ligand in the coordination sphere with a bound ion, e.g. B.
- a) [Co (NH 3 ) 5 (SO 4 )] Br (red), and
- b) [Co (NH 3 ) 5 Br] SO 4 (violet)
- Hydration isomerism
Hydration isomerism is a special case of ionization isomerism in which water molecules are involved as ligands. The particles in square brackets form the complex; the chloride ions outside the square brackets are only ionically bound:
- a) [Cr III (H 2 O) 4 Cl 2 )] Cl · 2 H 2 O (dark green)
- b) [Cr III (H 2 O) 5 Cl)] Cl 2 · H 2 O (light green)
- c) [Cr III (H 2 O) 6 ] Cl 3 (violet)
- Coordination isomerism
If both anions and cations are present as complexes in a complex, the ligands of central atom 1 can be exchanged for those of central atom 2.
Configuration isomerism of complex compounds
Analogous to the stereoisomerism of organic molecules, a distinction is made between complexes that have the same composition but a different spatial structure. Depending on the geometry of the complex, different forms of stereoisomerism can occur. The cis-trans isomerism is defined analogously to the diastereomerism in organic chemistry. It occurs, for example, with planar-square or octahedral complexes, but not with tetrahedral complexes.
If there are three identical ligands in an octahedral complex, a distinction can be made between fac (iale) and mer (idional) isomers.
If there is no rotating mirror axis in the molecule, enantiomerism naturally also occurs. In contrast to organic chemistry (4 different substituents on carbon) there is no simple rule when this is the case, unless the complex is tetrahedral coordinated. This is because coordination> 4 and chelate complexes can occur. So is z. B. cis- [Co (Br) 2 (en) 2 ] optically active, but not the trans form.
Significance in medicine / pharmacy
Pharmacological importance
In medicine , the stereoisomerism of drugs can be of considerable importance. Many drugs contain at least one stereocenter. The different enantiomers (isomers in the case of several stereocenters) can have different pharmacodynamic and pharmacokinetic properties; With regard to pharmacodynamics, this depends in particular on whether the stereocenter is located in a region of the drug molecule that is relevant for the drug-receptor interaction. If this is the case, then very often - but not always - only one of the enantiomers is responsible for the desired effects; this is also known as the eutomer . The other enantiomer (the distomer ) can contribute to the main effect, be ineffective, but in the worst case it can also be harmful or toxic. In the latter case, the distomer can be regarded as a 50% contamination of the active ingredient.
- Enantiomers
An example that is often used in this context is the drug thalidomide , which, as an effective component of the sleeping pill Contergan , led to numerous malformations in newborns in the 1960s ( Contergan scandal ).
- Enantiomers and diastereomers
The drug methylphenidate has two stereocenters. So there are four configurational isomers: (2 R , 2 ' R ) form, (2 S , 2' S ) form, (2 R , 2 ' S ) form and the (2 S , 2' R ) form . During the synthesis, the (2 R , 2 ' R ) form and the (2 S , 2' S ) form are formed as a racemate in the same amount. Furthermore, the racemate is formed from the (2 R , 2 ' S ) form and the (2 S , 2' R ) form during the synthesis . The racemate of the threo form, the (2 RS , 2 ' RS ) -methylphenidate, is used medicinally, although for fundamental considerations the use of an enantiomer which is more effective or has fewer side effects would be preferable. The pharmacological effect is mainly due to the D - (+) - form [D - (+) - methylphenidate, D- threo -methylphenidate, d-TMP, (2 R , 2 ′ R ) -methylphenidate].
Focalin ® , approved in the USA and Switzerland, contains only the (2 R , 2 ′ R ) -methylphenidate stereoisomer and is therefore effective even in lower doses.
Pharmaceutical-chemical importance
In classical chemical synthesis, a racemate is usually generated, i. that is, both enantiomers are present in equal proportions. If an enantiomerically pure end product is desired, an asymmetric synthesis strategy must therefore be followed. The separation of the enantiomers of racemic active ingredients by resolution can also be used to obtain enantiomerically pure drugs. Pharmaceutical active ingredients produced with the help of genetic engineering or fermentation are almost always enantiomerically pure. Alternatively, medicinal substances can also be isolated from natural substances (the chiral pool ), with enantiomerically pure products also being obtained as a rule.
Historical
Isomerism was discovered in the 1820s. The first example of this was the isomerism of silver cyanate (AgOCN) with silver fulminate (AgONC). Silver cyanate was analyzed in 1822 by Justus Liebig (together with Joseph Louis Gay-Lussac ), silver fulminate in 1823 by Jöns Jakob Berzelius . At first there was a dispute about the accuracy of the analyzes. After further examples of different substances with the same percentage composition had been found, e.g. B. ammonium cyanate and urea , it was finally recognized - initially by Gay-Lussac - that different substances can have the same quantitative composition. Berzelius, who in 1832 determined the same elemental composition for grape and tartaric acid , coined the term isomerism for it.
See also
Individual evidence
- ↑ Bernhard Testa: Fundamentals of organic stereochemistry. Verlag Chemie, Weinheim, 1983, ISBN 3-527-25935-X , pp. 128-130.
- ↑ a b E. J. Ariëns: Stereochemistry, a basis for sophisticated nonsense in pharmacokinetics and clinical pharmacology . In: European Journal of Clinical Pharmacology . No. 26 , 1984, pp. 663-668 , doi : 10.1007 / BF00541922 , PMID 6092093 .
- ^ D. Steinhilber, M. Schubert-Zsilavecz, HJ Roth: Medicinal Chemistry. Targets and Drugs . Deutscher Apotheker-Verlag, Stuttgart 2005, ISBN 3-7692-3483-9 .
- ↑ kompendium.ch: FOCALIN XR Ret Kaps 20 mg .
literature
- Ernest Ludwig Eliel, Arthur Lüttringhaus, Rudolf Cruse: Stereochemistry of carbon compounds. Wiley-VCH, Weinheim 1982, ISBN 3-527-25064-6 .
- Ernest Ludwig Eliel; Samuel H. Wilen, Henning Hopf , Johann Mulzer : Organic Stereochemistry. Wiley-VCH, Weinheim 1998, ISBN 3-527-29349-3 .
- Bernard Testa: Fundamentals of Organic Stereochemistry. Verlag Chemie, Weinheim 1983, ISBN 3-527-25935-X .
- Wolfgang Bähr, Hans Theobald: Organic stereochemistry. Springer, Berlin 1973, ISBN 3-540-06339-0 .
- Sheila R. Buxton, Stanley M. Roberts: Introduction to Organic Stereochemistry. Vieweg, Braunschweig 1999, ISBN 3-528-06996-1 .
- Karl-Heinz Hellwich: Stereochemistry - Basic Terms. Springer, Berlin 2002, ISBN 3-540-42347-8 .
Web links
- Constitutional Isomerism ( Chempage ) (last accessed November 2, 2012)
- Saarbrücken University : Lecture script stereochemistry (PDF, 499 KiB, last accessed on November 2, 2012)