From Big Medical Encyclopedia

FOSFORORGANYCHESKY CONNECTIONS — the organic compounds containing in the structure the phosphorus connected with a molecule of organic compound or a fos-for-carbon bond or through heteroatom — oxygen, nitrogen, sulfur. T. the pages which are partial esters of phosphoric acids (see) play extremely important biol. role; nucleic acids (see), phospholipids (see Phosphatides), phosphoproteins (see), etc. belong to such connections. Some F. pages apply as pharmaceuticals. The synthetic physiologically active connections which are full ethers or amides phosphoric to - t, with the general formula RiR2P are of special interest (About or S) X where Ri and R2 — alkyl or alkoks ilny radicals, the replaced amides, X — acid group (fluorine, nitrophenols, mercaptans, anhydrite groups). Biol. activity F. by page of this group it is connected with the fact that they act as inhibitors (see) cholinesterases (see Antikholinesterazny means). At the heart of classification and the standard nomenclature such F. pages lie phosphoric to - you, derivatives to-rykh they are. So, the chemical name of Arminum (see), derivative ethyl - phosphonew to - you. About-ethyl-au-m-nit-rofeyailetilfosfoyaat........

Characteristics of certain representatives F. page watch in articles Antikholinesterazny means, Arminum, Nibuphinum, Neuroparalytic toxic agents, the Pirofos, Phosphacolum, Hlorofos.

The mechanism in z and and m about d e fi-St in and I f about with f about r about r and N and h the EU to and x connections about sincaline-e with t of e r and z and m and. The Esterazny center of an active surface of cholinesterases (see) includes at least two functionally important groups — an imidazole of the rest of a histidine (see) and hydroxylic group of the rest of serine (see). At sorption F. page on the catalytic surface of cholinesterase (HE) between fos-forilny oxygen F. the page, an imidazole of a histidine and hydroxylic group of serine through system of hydrogen bindings form cyclic enzyme - an inhibitory complex, enzyme, similar on structure, - substrate to Mikhaelis's complex (see Enzymes). Redistribution of electrons leads to eliminating of acid group N • X and to education fosforilirovan-ache on hydroxylic group of HE serine, and such intermediate compound unlike the acylated HE (at its reaction with substrate) is almost incapable of hydrolytic eliminating of fosfo-rilny group and recovery of activity of enzyme (see Phosphorylation). It defines the irreversible nature of oppression of HE under the influence of F. the page, however hydrolysis of fosforilirovanny HE can occur under the influence of nucleophilic reagents — reaktivator. Quantitative measure of anti-fermental action F. the page serves a dimolecular reaction rate constant ki (M-1 * sec. "1-or M" 1 * • mines-1). Earlier as such measure served the size of concentration F. page, HE causing oppression for 50% (I50, M).

At development of acute intoxication F. page the leading role is played by their antikholinesterazny effect. Assume that a certain value has neantikholinesterazny action F. page directly on a holinoretseptor.

Metabolism of fosforor-@ and N and h e with to and x connections. On V. I. Rozengart's hypothesis, all metabolic transformations F. pages lead to formation of more polar products that facilitates their removal from an organism, and generally proceed under the influence of certain groups of the enzymes belonging to the classes of hydrolases (see), transferases (see), oxidoreductases (see). In an organism F. pages are exposed also to non-enzymatic transformations, napr, to eliminating of a molecule salt to - you in the course of metabolism of a hlorofos, a tiontiolny isomerization. Metabolic transformations F. pages in an organism can lead both to an inactivation (detoxication) of organophosphorous connections, and to their activation.

Practical application fosfororgan and chesk x connections. Main practical use F. the page as acaricides (see) and insecticides (see) is connected by hl. obr. with their high biol. efficiency and with a bystry detoxication (in comparison, e.g., with organochlorine compounds). To serious shortcomings F. the page concerns their certain toxicity concerning the person and domestic animals and easily arising resistance to them at arthropods (see Herbicides, Dezinsitsiruyushchy means, Larvicides, Pesticides).

Extremely important role played F. page in researches of the HE properties received from various sources. By means of big group specially synthesized F. the pages having unpolar hydrocarbon radicals on a catalytic surface of molecules HE the hydrophobic sites which are of great importance in manifestation by these enzymes of substrate specificity were found.

T. pages as pharmaceuticals apply at treatment of glaucoma, to the prevention and treatment of a postoperative atony of a stomach and intestines, and also at injuries and inflammatory diseases of bodies went. - kish. a path (see Antikholinesterazny means, Armin, Nibufin).

Bibliography: O'Brayn R. Toxic ethers of acids of phosphorus, the lane with English, M., 1964, bibliogr.; Rosen metal V. I. and Sherstobitov O. E. Selective toxicity of organophosphorous insectoacaricides, L., 1978; Gardens -

A. S's k., etc. Cholinesterases, Active center and mechanism of action, Tashkent, 1976; Chemistry and use фосфор^ organic compounds, Works of the First conference, under the editorship of A. E. Arbuzov, M., 1957; E

to M. Organophosphorus pesticides, Organic and biological chemistry, Clevelend, 1976, bibliogr. E. V. Rozengart.