Organophosphorus compounds (OPCs) are used in many areas of human activity. Unique physicochemical properties and high biological activity not only determine the applied value of OPCs but also give them the properties of xenobiotics that are harmful to human health, which largely depend on the state of the endogenous microbiota. The purpose of this work is to assess the effect of pyridyl- and aryl-containing phosphines, their oxides, and sulfides on the growth of Bifidobacterium bifidum and Escherichia coli and to identify possible patterns of biotransformation of OPCs using 31P NMR spectroscopy. Bacteria were cultivated in thioglycollate medium containing the tested phosphorus compounds. At the stationary growth phase was determined the cell concentration and were recorded spectra 31P NMR. It was shown that the most reliable (p<0,05) and opposite effect on the growth dynamics of both species of bacteria was exhibited by phosphine sulfides 1 and 3: PS1 (pyridyl) reduced the population reproduction rate by 35–40%, and PS3 (aryl) increased it by 45–60%. At the same time, OPCs themselves were most likely not metabolized. Phosphine oxides reduced the average titer of bacteria compared to the control, and PO3 caused complete cell elimination after 24 hours cultivation. In the medium with PO2 was identified PS2 appeared, which may be caused by the biologically mediated process of oxide-to-sulfide conversion. All phosphines are chemically labile and they were oxidized abiotically to oxides and sulfides. Formed sulfides could be the reason for a significant increase (to 35%) in the growth rate bacteria population both species. Five new unidentified organophosphorus compounds (UPC) were recorded on medias with B. bifidum, some of which may belong to the products of biotransformation of the original OPCs. Some organic phosphates, homologous to the phosphine oxides tested, have a δp value neighboring to the taken NMR spectra. This may indicate the way of their biological transformation: oxidation of the CP bond in the phosphine oxides to an ester bond of organic phosphates. This ability of bifidobacteria to metabolize OPCs will make it possible to develop a therapeutic strategy based on the use of B. bifidum as a microorganism that degrades phosphorus-containing xenobiotics.

Background. Molecular structures combining a phosphorus-containing counterpart and non-polar radicals are employed in design of pro-drugs as structural and functional groups necessary for transportation of drugs through cellular barriers. It is assumed that the carrier itself does not exhibit biological activity. However, the “organic phosphate – alkyl radical” complex may possess its own metabolic and pharmacological properties even in the absence of a drug moiety.The aim. To study the effect of fluorinated alkyl phosphates on the growth of bacterial test cultures in an agar medium and to identify conjugated metabolic markers using UV/visible spectroscopy.Materials and methods. The effect of six organyl phosphates on the growth of five types of bacteria under aerobic conditions was evaluated by the method of wells in an agar medium. For solutions containing cell metabolites of Pseudomonas aeruginosa, the absorption spectra were recorded at 250–280 nm. The principal component analysis (PCA) was used for multivariate comparative analysis of the spectra. Results. The studied organyl phosphates bearing the ethyl and propyl radicals are potential temporary carriers of the drug moiety, since they are capable of penetrating through cellular barriers. However, the fluorinated compounds exhibit bactericidal properties, the degree of which depends on the arrangement of fluorine atoms in the radical. The most active compounds are those exhaustively halogenated at the terminal carbon atom of the ethyl radical (-СН2-СF3), while non-fluorinated organyl phosphate is the least active. UV/visible spectra of P. aeruginosa cultivation products, according to PCA data, contain patterns reflecting the metabolic effects mediated by these structural features of the radicals.Conclusion. In terms of practical application of the studied compounds, the activity of a proantibiotic based on organyl phosphate with a non-fluorinated ethyl(propyl) radical will be determined only by the specificity of the drug moiety. Exactly the same molecule, but exhaustively fluorinated at the terminal carbon atom of the alkyl radical, is likely to be characterized by lower specificity and higher activity under the additive (or synergistic) action of metabolically active groups.

Halide ions are a type of anions that are commonly found in the environment, have important physiological functions, and are used in industry. However, their high content is harmful to the environment and human health, largely depending on the status of the endogenous microbiota. The aim of this work is to research the features of the influence of halides on Bifidobacterium bifidum growth in vitro. The dependence of biomass accumulation in the stationary phase on the content of sodium and potassium halides in thioglycol medium at different concentrations (0,001, 0,01, 0,1 and 1 M) was studied. Empirical values were fitted with dose-response model curves. Two-factor PERMANOVA was shown that the shape of the curves significantly (p<0,01) depends on the type of anion, type of cation, salt concentration and the interaction of factors “type of anion / salt concentration”. Moreover, the biomass of bacteria is often lower in the presence of potassium salts than similar sodium ones. As a result, model curves for different salts has various form (logistics, exponential and hyperbolic). Fluorides and chlorides inhibited biomass growth at all concentrations compared to control. Bromides and iodides at 0,001–0,01 M stimulated the accumulation of biomass to 20–50%. This effect can be used in the food industry, agriculture and healthcare. At a concentration of 0,001 M, a significant regression relation was shown between the atomic mass of the halogen and the fitted curve value of biomass. This dependence probably demonstrates effect atomic radius or/and electronegativity halogens for their penetration into the cell and interaction with cellular targets. The result dependencies do not correspond with state sanitary standards for halide ions. These regulations for fluorides (~10–4 M) and chlorides (10–2 M) roughly match to the survival limit of bifidobacteria. However, more strong limits for bromides (~10–6 M) and iodides (~10–6 M) do not correlate with the biological response of bifidobacteria. In addition, the sanitarian standards halogenids do not take into account the modifying effect of cations which can be important.

Полифторалкилдихлорфосфаты легко реагируют с пропаргиловым спиртом в достаточно мягких условиях (22-62°С, 3 ч, пиридин-толуол), образуя неизвестные ранее бис(2-пропинил)полифторалкилфосфаты с выходом 36-41%, тройная связь в которых способна участвовать в реакции азид-алкинового циклоприсоединения.

Polyfluoroalkyl dichlorophosphates react easily with propargyl alcohol under mild conditions (22–62°С, 3 h, pyridine-toluene) to form previously unknown bis(2-propynyl) polyfluoroalkyl phosphates with a yield of 36–41%, a triple bond in which is capable of participating in the azide-alkyne cycloaddition reaction.

Bis[2-(4-pyridyl)ethyl]phosphine reacts with acrylonitrile under mild conditions to form bis[2-(4- pyridyl)ethyl](2-cyanoethyl)phosphine which is readily oxidized in air to the corresponding bis[2-(4-pyridyl)- ethyl](2-cyanoethyl)phosphine oxide. The latter compound reacts with 1,4-dihalobutanes according the scheme of polyquaternization with practically quantitative formation of high-molecular cationic compounds (ionenes) bearing phosphine oxide groups and pyridinium cycles in the main chain. The thus obtained ionenes enter the intermolecular interaction with anionic polyelectrolytes (polyacrylic acid, heparin). They were also found to exhibit antibacterial activity.

Polyquaternization reactions of bis[2-(4-pyridyl)ethyl]phenylethylphosphine oxide and tris[2-(4-pyridyl)ethyl]phosphine oxide with 1,4-dibromobutane were implemented for the first time to give linear (water-soluble) and cross-linked (limitedly water swelling), respectively, representatives of new phosphorus- and nitrogen-containing ionenes. The synthesized linear ionenes react with heparin and polyacrylic acid yielding water-insoluble polyelectrolyte complexes.

Phosphine generated from the red phosphorus in the system KOH-H 2 O-toluene adds regio- and chemoselectively to vinyl sulfides under radical initiation conditions with the formation of tris(2-organylthioethyl)phosphines, which are easily oxidized by elemental sulfur and selenium to the corresponding phosphine sulfides and phosphine selenides in 54–78% yield. The obtained adducts are split when treated with sodium amide in THF to give trivinylphosphine and trivinylphosphine chalcogenides.