From Big Medical Encyclopedia

COMPLEXONS — the organic matters forming strong complexes with cations of many metals; combine in a molecule osnovny (more often the nitrogen atom, is more rare than trivalent phosphorus) and acid (as a rule — COOH — PO 3 H 2 ) centers. To. use in medicine as antidotes at poisonings with salts of heavy metals and lanthanides (rare earths) and in some other cases, and also as antioxidants at storage of medicines, vitamins and donor blood, as elyuant at division of mixes of lanthanides and other relatives to them on properties of elements. To. apply to washing tekhnol. the equipment from insoluble deposits and in the textile industry.

The term «complexons» was for the first time offered in 1945 by the Swiss chemist G. Schwarzenbach for organic ligands (ligands — the neutral molecules or ions of an opposite charge which are coordinated around the central ion; sometimes they are called by addendam) groups polyaminopolyacetic to - t, such as nitrilotriacetic, ethylene diamine tetraacetic, etc. Later To. began to call also polyaminopolyphosphonew, oxyalkylidenedilphosphonic to - you and related connections it.

The usual nomenclature of organic compounds is applicable also to K. Odnako in scientific and furthermore in technical literature generic and branded names often meet. So, nitrilotriacetic to - that is designated also NTA, Trilonum And, a complexon of I, Titriplexum of I; ethylene diamine tetraacetic to - they are EDTA, a complexon of II, Versenum; its disodium salt — Trilonum of B, a complexon of III, etilendiamindiizopropilfosfonovy to - that is fosfitsin.

To. represent crystal substances, as a rule, insoluble in alcohol and in the majority of organic solvents; they are rastvorima in to-takh and alkalis, is more rare in water. As well as amino acids, the majority To. are in solution and in a firm look in a betainovy form (betaines call intramolecular salts of the quarternary bases: ammonium, oxonium and sulphonium). Acid dissociation of the polymain to - t is carried out consistently: to pH 5,0 — 6,0 there is, as a rule, a dissociation of acid groups, at> pH 7,0 — betainovy groups.

Main distinctive property K. their ability to form high-strength is complex connections (see) with the majority of cations of metals, steady in aqueous mediums, including and with cations of alkaline earth metals; their interaction with cations of alkali metals is less characteristic. The complex formation is carried out by means of donorny atoms (the nitrogen, oxygen, sulfurs are more rare, than phosphorus-III) capable to provide not divided couples of electrons to vacant orbitals of a metal cation. Depending on number of donorny atoms distinguish complexing agents (ligands) trekhdentatny, chetyrekhdentatny etc. Respectively, in the formed complex two become isolated, three etc. numbers of cycles with metal (metalcycles). The similar complex connections formed by polidentatny ligands and containing several metalcycles are called chelates or claw-shaped connections. The bigger number of cycles becomes isolated in the formed complex, the it is steadier. So, EDTA is a shestidentatny ligand, the complex of cobalt contains five metalcycles.

Durability of the formed complex is characterized by a constant of stability (To). In the elementary case To = [ML] / ([M] [L]) where [ML] — concentration of a complex in solution, [M] — concentration of free metal, [L] — concentration of a free ligand. Durability of the formed complexes in most cases increases in the following sequence:<<< Be Mg Ca Fe 2+ < <<<<Mn Co CD Pb Fe 3+ .

By 70th 20 century more than 200 connections of a class K are synthesized. Detailed studying of their complexing properties allowed to reveal influence of a structure of a molecule on specifics of a complex formation and to create ligands with required properties. So, phosphorus To. (fosfitsin, etc.), phosphonew containing instead of carboxyl groups, have a number of unique properties: they are capable, unlike karboksilsoderzhashchy analogs, to a complex formation at low pH values, form strong complexes with transition elements, practically without interacting with calcium that is very important for their use in medicine (tab.); their complexes with cations of small and large atomic volume (beryllium, germanium, uranium) differ in big stability. To., the containing alkoxide and oxyaryl radicals, show selectivity to metals which salts are easily hydrolyzed, especially to iron, forming with it very strong complexes steady even at high pH values.

To. an aromatic series, the containing high-conjugated systems of bonds (ftaleina, naftalina, stilbenes), have ability to change coloring or intensity of a luminescence at interaction with cations. It results from interface of donorny nitrogen atoms (or oxygen) with system of double bonds that causes change of an electronic condition of a molecule in the course of a complex formation. Similar property K. allows to use them as analytical reagents what kompleksonometrichesky metalindicators — ksilenolovy orange are, e.g., ftalekson etc. (see. Kompleksonometriya ).

New opportunities are opened by area of the mixed complex formation. At the same time the cation-kompleksoobrazovatel at the same time interacts with a molecule K. and with a molecule of an additional ligand — haloid, amine, amino acid. The formed mixed (triple) complexes differ in durability and a number of specific properties.

In a human body To. form with ions of two - and trivalent metals (lead, cadmium, mercury, copper, etc.) complex connections which difficult dissociate, well rastvorima in water are rather quickly removed with urine and are a little toxic. The main number of complex connections are brought out of an organism by kidneys. Efficiency of use To. at intoxication metals depends as on a structure To. and their physical. - chemical properties, and from complex processes of circulation, deposition of ions of toxic metals and ways of their removal from an organism. Great value have competitive relations between To. and the bioligands which are contained in an organism fixing metals such as proteins, nucleinic to - you, amino acids, etc. The greatest effect To. render at acute intoxications metals, in t. e. in conditions when there is no strong communication between ions of toxic metal and bioligands in an organism yet; these ions are fixed in depot — in bones and parenchymatous bodies in rather small amounts. To. in an organism can connect also calcium ions which concentration in blood is rather high. In certain cases this effect has positive value, leading to removal from an organism of excess of calcium.

The main representatives To. derivatives polyaminopolycarboxylic to - t are used as pharmaceuticals: EDTA, its calcium - disodium salt (see. Tetacinum-calcium ) and disodium salt (see. Ethylene diamine tetraacetic acid disodium salt ), and also trisodium - calcium salt dietilentriaminopentauksusny to - you (see. Pentacinum ). Relatives on the mechanism of action to To. derivatives of dimethylcysteine are (D-Penicillaminum) and Deferoxaminum. For treatment hron, poisonings with metals use D-Penicillaminum which is appointed only by per os.

D-Penicillaminum is applied to binding of copper at patol, increase in its contents in an organism and, first of all, to treatment of hepatocerebral dystrophy (Wilson's disease — Konovalova). Drug at prolonged use causes substantial increase of excretion of copper, the wedge reduces sharpness, symptoms and improves functioning of a liver. Drug renders also therapeutic effect at a hemosiderosis, increasing release of iron, and at a nefrolitiazisa, regulating exchange of calcium. Due to the oppressing influence on synthesis of D-Penicillaminum collagen apply to treatment of a scleroderma and some forms of rheumatic diseases (e.g., rhematoid polyarthritis).

Specific antidote at poisoning with salts of iron is Deferoxaminum. This drug is administered intravenously also by per os.

Deferoxaminum selectively brings excess of iron out of various ferriferous proteins — ferritin, hemosiderin, etc. in this connection it is applied at primary and secondary hemochromatosis, including transfusion a hemosiderosis, at some types of anemia and at a porphyria.

For acceleration of removal of radioisotopes use hl. obr. Pentacinum.

The EDTA disodium salt in connection with its ability to delete calcium from an organism is applied at disturbances of a rhythm of cordial reductions (at digitalis tachyarrhythmias, ventricular extrasystoles and an atrioventricular block). In these cases drug is means of the emergency help to patients since intravenous administration of drugs of potassium is extremely dangerous or contraindicated. Bystry antiarrhytmic effect To. allows to prevent increase of frustration of a hemodynamics and to win time for regulation of electrolytic balance of an organism by purpose of salts of per os potassium. Drug is shown also for treatment of the diseases connected with patholologically excess adjournment in an organism of salts of calcium: patol, ossification of a skeleton, arthritises with adjournment of calcic salts, etc., and also for expansion of root channels of tooth by decalcification of oxyapatite of dentine.

To. are relatively small toxics. However they can cause quite heavy side effects connected with the fact that To. form complex connections not only with those metals which need to be brought out of an organism, but also with others, necessary for it. In this regard manifestations of a hypocalcemia are possible (especially during the use of Na 2 EDTA), gipokupremiya, etc. Formation of complex connections with ions of metals can cause irritation of a wall of a vein at infusion or a mucous membrane went. - kish. a path that leads to a number of the local and general phenomena: morbidities on the course of a vein, feeling of heat, dizziness, vomiting, etc. Bystry intravenous administration To. can cause a collapse. At long introduction To. are sometimes observed an aggravation a wedge, displays of intoxication, change of coagulant system of blood, white blood, a hemoglobin content, etc. Especially it should be noted disturbances from kidneys through which there is an allocation of the main number of complex connections; at use of D-Penicillaminum and Deferoxaminum the phenomena of a sensitization and a toksikodermiya can appear.

For prevention of possible side effects it is necessary to adhere strictly to application instructions of the drugs which are To.

Table. The Pharmako-klinichesky characteristic of the pharmaceuticals which are complexons

Bibliography: Albert E. Selective toxicity, the lane with English, page 282, M., 1971; Arkhipova O. G., 3 about r and N and L. A. and Sorkin N. S. Complexons in clinic of occupational diseases, M., 1975, bibliogr.; And sh e of l S. I. and d river. About prevention of a professional mercurialism at workers of production of a granozan new Soviet antidotom-D-pevi-tsillaminom, the Gigabyte. work and the prof. having got sick., No. 7, page 25, 1974, bibliogr.; D I am t-lovan. M, Temkinav. I. and Kol-pakova I. D. Complexons, M., 1970; Kabachnikm. And., etc. Organophosphorous complexons, Usp. chemistry, t. 43, century 9, page 1554, 1974, bibliogr.; Mashkovsky M. D. Pharmaceuticals, p. 2, page 124, etc., M., 1977; Chemistry and use of organophosphorous connections, under the editorship of M. I. Kabachnik, page 497, M., 1972, bibliogr.; Shvartsenbakh V. and G. Kompleksonometricheskoye's Tag titration, the lane with it., M., 1970, bibliogr.; R u i z-T o of of e s A. Zur Pharma-kokinetik und zum Stoffwechsel von D und L Penicillamin, Arzneimittel-Forsch., Bd. 24, S. 914 u. a., 1974, Bibliogr.

H. M. Dyatlova, B. Ya. Temkina; Ya. I. Hadzhay (pharm., tab.).