From Big Medical Encyclopedia

ISOMERISM (grech, isos equal, identical + meros a share, a part) — the phenomenon which is that some substances having identical qualitative and quantitative structure and identical molecular weight can possess various structure (i.e. order of compound of atoms in a molecule) or various spatial relationship of atoms or atomic groups; such distinctions are the reason different physical. - chemical and biol, properties of these substances called by isomers. The space structure of a molecule influences in a decisive way properties and biol, functions of the organic matters participating in processes of life activity: it belongs to proteins and amino acids forming them, nucleinic to - there, to sugars, steroid hormones, natural oxyacids, enzymes, vitamins, etc. E.g., the photochemical processes happening in a retina of an eye include obligatory transition of a retinal to the stereoisomer (see. Rhodopsins ). It is necessary for resynthesis of a rhodopsin that the retina received cis-isomer of vitamin A. Any question medical or biol, chemistry cannot be solved without stereochemical factors, i.e. without I.

Vpervye I. phenomenon Yu. Libikh who in 1823 found out that silver salt rattling to - you the same chemical structure, as silver salt cyanic to - you received in 1822 by F. Voeller have absolutely other properties, in particular property to blow up observed. The term «isomerism» was entered by I. Bertselius in 1830. Essence And. received the correct explanation only after creation of the theory of a chemical structure by A. M. Butlerov, according to a cut of property of substance depend not only by nature and amounts of the atoms which are a part of its molecule but also on an order of their connection.

Distinguish two main types And.: structural, caused by various order of compound of atoms, and space (stereoisomerism), edges it is characterized by the fact that at the identical sequence of compound of atoms in a molecule their arrangement in space variously.

Structural And. it is observed at distinction of a carbon skeleton of molecules (the chain of C-atoms can be direct or branched), and also at the different provision of this or that functional group in relation to equally constructed chain of C-atoms. E.g., three isomers of hexane with the general formula C 6 H 14 have such structure:

With increase in number of atoms the number of possible isomers quickly increases in a carbon chain. In an aromatic series of hydrocarbons derivatives of benzene with two and three deputies have three isomers:

Unsaturated hydrocarbons can be isomeric as owing to And. a carbon chain, and owing to various situation — C = C — or — C = C — bonds, e.g.:

There is a special sort I. — the metamerism, edges is defined by distinction of the radicals connected with multivalent atom-organogen, e.g.:

CH 3 CH 2 - O-CH 2 - CH 3 [diethyl («sulfuric») ether];

CH 3 - O-CH 2 CH 2 CH 3 [methyl-propyl ether].

Physical. and chemical properties of isomers are various. For the isomers relating to one homologous series, napr, unsaturated hydrocarbons, differences in physical are most characteristic. properties. If isomers differ under the provision of a functional group, then and their chemical properties are various, and these differences can be brightly expressed as, e.g., at glycine and amide glycolic to - you:

NH 2 - CH 2 - COOH [glycine] and HO-CH 2 CONH 2 [amide glycolic to - you]

the Special look And. is tautomerism (see), edges it is characterized by the fact that two (or more) isomer (tautomer) spontaneously pass each other until between them balance is not established.

Space And. (stereoisomerism) includes two main types: geometrical, or cis-a trance isomerism, and optical, or mirror, I.

Tsis-trans-isomers differ from each other in various arrangement of atoms or groups of atoms in relation to the plane of a double bond or the plane of a ring (cycle). In that case when certain atoms or groups of atoms are on one side of a double bond (or rings), connection is cisisomer when similar atoms or groups of atoms are on different sides from a double bond (ring) — trans-isomer. Cis-trans-isomers differ from each other on physical. and to chemical properties, however usually one of them is less steady and passes into another under the influence of uv radiation, heating, etc.

One of forms of a stereoisomerism is the sin-anti-isomerism observed among organic compounds in which molecule trivalent nitrogen is connected by a double bond to carbon atom, t. e. With = N —. Aldoksima and ketoximes are an example of such isomers.

Among aldoksim what have a hydroxylic group (OH —) are considered as sinizomer and hydrogen are on one side of a double bond:

Sinizomera differ from anti-isomers in stability. This look And. takes place and when the molecule contains two nitrogen atoms connected by a double bond, napr at azo compounds (see) and diazo compounds (see).

the Diagrammatic representation of optical (mirror) isomerides of lactic acid — the D (a) and L.

At optical, or mirror, And. molecules of isomers are similar at each other as mirror images, but cannot be combined (fig). Such substances have optical activity, i.e. can rotate the plane of polarization of light to the right [D-, or (+) - isomers] or to the left [L-, or (—) - isomers]. Since molecules of such isomers are similar at each other as they the right and left hand, and are also incompatible, them call still chiral (grech, cheir a hand). All optical isomerides contain asymmetric carbon atom, i.e. the atom connected to four various atoms or groups of atoms. During the writing of formulas such C-atoms note an asterisk (C *). Usually optical isomerides possess similar physical. and chemical properties, except for sign of rotation of the plane of polarization of light; besides, in certain conditions such substances form the crystals similar at each other as mirror images. This phenomenon carries the name «enantiomorphism»; optical antipodes are called respectively enantiomorfny forms. Mix of equal quantities of optical antipodes is called by racemic substance or a racemate, and by the substances making it — racemates.

Under certain conditions one optical antipode can turn into another. This transformation was for the first time studied by P. Walden in 1895 on apple to-takh and afterwards received the name of Walden Inversion. It was the first observation from the field of dynamic stereochemistry of reactions.

In process of increase in number of the known optically active connections there was a need to find some criterion, on Krom they could be compared. It was convenient, according to M. A. Rozanov (1906) proposal, to take for a standard an arrangement of atoms and their groups around asymmetric C-atom in a molecule glyceraldehyde (see):

The substances having the arrangement of atoms or their groups at S*-atoma corresponding to that at D-glyceraldehyde began to consider substances of a D-row, or D-configuration, and dexter right and laevus left was offered to carry the substances having an arrangement of atoms at S*-atoma, close to that at S*-atoma of L-glyceraldehyde to substances of a L-row, or L-configuration (Latin). Not always D-isomer rotates the plane of polarization of light to the right, and L-isomer to the left since sign of rotation is defined by all groups, a D-or L-accessory is determined generally by an arrangement of H-and OH-group. Such designations as D (—) - pentose or L (+) - hexose can meet. Therefore lowercase letters of «d» - and «1» - apply when it is only about sign of rotation, and the configuration either is not known, or is not important.

If in connection there are two asymmetric centers, it can form treo-and eritro-isomers. The names «eritro» and «treo» come from names of carbohydrates erythrose and threose:

Treo-isomers have identical pendent groups on the different parties of a standard projective formula, and at erythro-isomers two identical pendent groups stand in a projective formula on one party (on the right or at the left). Two erythro-isomers represent couple of optical antipodes during which mixing the racemate is formed; the same treats also treo-isomers.

At further increase in number of the asymmetric centers the number of stereoisomers increases, and each new asymmetric center doubles number of isomers, a cut is equal to 2 n , where n — number of the asymmetric centers.

The role of steric factors in biochemical, processes for the first time was noted by L. Pasteur in 1857, observing preferential destruction by nek-ry microorganisms of a dextrorotatory form wine to - you. It turned out that if to treat to action of such microorganisms a racemate wine to - you, then it is possible to save up a significant amount of a left-handed antipode.

P. Ehrlich at the beginning of 20 century described the same phenomenon for amino acids: some yeast in process fermentations (see) processed preferential L-amino acids, and their optical antipodes collected in cultural liquid. Thus it was succeeded to receive with an exit to 60 — 70% optically pure D - izome-ry alanine, valine, a leucine, an isoleucine, from about in Alija and, serine, phenylalanine, etc.

The crucial role in stereospecificity biochemical, processes is played by existence in a live organism spatially of the selective enzymes catalyzing transformations only of certain stereoisomers. H. D. Dakin in 1903 observed stereospecific action of the lipase allocated from a liver of a pig at hydrolysis of ethers almond to - you and related connections. Stereospecificity of phosphatase was found in 1905 by K. Neyberg. Enzymes are capable to catalyze asymmetric sinteza therefore from racemates optically active reaction products turn out. This ability of enzymes shows a way, on Krom in live organisms optical activity remains, reproduced and «breeds». The fact that in wildlife certain space forms meet is explained by it: amino acids (in proteins) only a L-row, sugar preferential a D-row.

Indiscernible on physical. and to chemical properties optical antipodes differ on the fiziol, action often markedly. So, alkaloid of tobacco — left-handed nicotine — is several times more poisonous, than dextrorotatory nicotine; dextrorotatory asparagine has sweet taste, and its optical antipode is tasteless. Natural L - glutamino-vaya to - that has taste of meat and is used as flavoring additive at production of food concentrates, and D-glutaminic to - that is tasteless.

Activity of growth stimulants is also often connected with their space structure. So, (+) - alpha 3-indolylpropionic to - that is 30 times more active (—) - isomer; cis-cinnamon to - that is capable to accelerate growth of plants whereas trans-cinnamon to - that is in this respect inactive.

Also insecticidal drugs have stereospecificity. Only one of eight stereoisomers of hexachlorocyclohexane, so-called gamma isomer, has insecticidal activity. The same pattern is noticed also concerning DDT stereoisomers.

Spatial configuration also is of great importance for the substances possessing pharmakol, activity. E.g., L - dioksifenila-lanin (L-DOFA, a levodopa) with success it is used at treatment of some nervous diseases (see. Dioksifenilalanin ), whereas D-DOFA pharmakol, has no activity. From two antipodes of adrenaline stronger hormonal action also shows laevoisomer.

Only one of four stereo-isomers of Chloromycetinum — left-handed treo-isomer — is an active antibiotic, other stereoisomers are absolutely inactive.

The left-handed form of sarcolysine is active at treatment of some types of tumors, dextrorotatory — is inactive.

PASK (p-aminosalicylic to - that) possesses pharmakol, activity at treatment of tuberculosis whereas its structural isomers (orto-and meta-) do not possess antitubercular action.

The received synthetic antipode of natural (—) - morphine does not possess soothing action. Such examples it is possible to bring much. Data are obtained that psoriasis is a disease of a metabolism, at a cut the isomerization cis-of isomer (fumaric to - you) in trans-isomer is broken (maleic to - that):

Stereospecificity biol, processes finally is caused by the fact that live organisms «are constructed» of optically active asymmetric material. A figurative analogy was drawn by L. Pasteur: if to screw in in a board screws with the right and left cutting, they will enter a board with identical ease, however if to screw in the screw in an opening, a cut already has cutting, it is possible to make it only if the directions of both cuttings correspond each other.

In biol, systems of interconversion of various isomers catalyze the enzymes belonging to the class isomerases (see).

A rotary isomerism — see. Conformation .

The isomerism of atomic kernels is caused by existence at some nuclides of a so-called metastable state, i.e. excited state of a kernel with unfavourable transition in the basic and possessing therefore rather big time of life in comparison with the usual time of life of excited state of kernels making size about 10 - 13 sec. Phenomenon And. atomic kernels it is observed, as a rule, when distinction of spins of the ground and excited state is big. Metastable states happen as at stable, and, hl. obr., at radioactive nuclides. In the latter case the nuclide generally and a metastable state can conditionally be considered as two nuclides with identical atomic number and mass number, but with different schemes of radioactive decay — half-lives, type and a radiation energy.

Disintegration of metastable states most often happens by transition from this nuclide excited (higher) to the ground power state to emission of gamma radiation or electrons of internal conversion that is called isomeric transition.

It is known apprx. 150 isomers of nuclides with half-lives from fractions of a second up to several years. Separate nuclides have several different metastable states, i.e. several isomers which are breaking up with different half-lives (e.g., 124M Sb with T 1/2 1,3 min. and 24 min.). Many short-lived nuclides which are breaking up by isomeric transition with emission of gamma radiation rather small energy are successfully applied in radio isotope a wedge, researches.

Bibliography: Alpha, beta and gamma spectroscopy, under the editorship of K. Zigban, the lane with English, century 1 — 4, M., 1969; The Benefits To., the P e r in and N-kao. ikovarya. Fundamentals of stereochemistry and conformational analysis, the lane with English, L., 1974, bibliogr.; Brooms S. N., Kuznetsov S. G. and Zatsepin E. P.’ Stereospetsifichnost of effect of medicinal substances, L., 1973, bibliogr.; Klabunovsky E. I. Asymmetric synthesis, M., 1960, bibliogr.; Potapov V. M. Stereochemistry, M., 1976; Stepanenko B. of H. A course of organic chemistry, p.1 — 2, M., 1976.