DEPENDENCE «STRUCTURE – TOXICITY»OF THE METHYL DERIVATIVES OF PYRIDINE AND PYRIDINEN-OXIDE

Vasetstka O. P., Prodanchuk M. G., Zhminko P. G., Dulnev P. G.

HYGIENE AND ECOLOGY

Scentific article

The purpose of the work.Determine the dependence of acute toxicity of methyl derivatives of pyridine and pyridine-N-oxide and complexes pyridine-N-oxide with organic acids on their structure and physico-chemical properties. Methods.Toxicological methods –acute toxicity (LD50), physico-chemical methods –calculation of the constants log Ro/w by the program EPIWEB 4.1 and the values of charges on the nitrogen atom of pyridine and N-oxide of pyridine using the Natural Bond Orbital (NBO) method. Results and conclusions.The dependence of acute toxicity on the chemical structure and physical-chemical properties for pyridine, pyridine-N-oxide, their methyl derivatives and pyridine-N-oxide complexes with organic acids (total 23 substances) was studied. It is shown that they are moderately or low-toxic substances. The toxicity of methyl derivatives of pyridine and pyridine N-oxide depending on the physical and chemical properties varies slightly. Methyl groups in the structure of pyridine and pyridine-N-oxide irrespective of the position in the molecule increase their toxicity by 2-3 times. Pyridine- N-oxide is 2.7 times less toxic than pyridine, which is due to the presence of oxygen near the nitrogen atom of the pyridine ring, the magnitude of the nitrogen atom charge and less lipophilicity. With decreasing charge on the nitrogen atom in molecules of methyl derivatives of pyridine and pyridine-N-oxide, their toxicity increases. The toxicity of complexes of pyridine-N-oxide and its methyl derivatives with organic acids varies depending on the structure of the proton donors. Formic, oxalic and maleic acids increase the toxicity of pyridine-N-oxide and its methyl derivatives, and succinic acid reduces it. The toxicity of complexes of pyridine N-oxide with organic acids can be due to changes in the state of hydrogen bonds with oxygen N +→O and hydrogen as a result of their interaction.

pyridine, pyridine N-oxide, methyl derivatives, acute toxicity, structure-toxicity dependence

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«Bulletin of problems biology and medicine» Issue 1 Part 1 (142), 2018 year, 84-92 pages, index UDK 615.9 + 615.015.11+547.823

10.29254/2077-4214-2018-1-1-142-84-92