Vol 93, No 6 (2023)

The acid-catalyzed reaction of 1-(2,2-dimethoxyethyl)ureas with aromatic and heterocyclic nucleophiles leads to the formation of new imidazolidin-2-ones. The proposed method makes it quite easy to introduce the required pharmacophore group into position 4 of the imidazolidine cycle.

2,3-Dihydro-1 H -imidazo[1,2- a ]benzimidazole in acetic acid, and its N ¹-Me derivative in CHCl₃, are brominated at position 6 with bromine. Less nucleophilic N ⁹-R derivatives do not enter into the reaction under these conditions, but, like their N ¹-R isomers, they are quite effectively brominated by the KBrO₃-HBr system, but at position 7, probably due to the transition of the reaction to the mode of bromination of protonated forms of substrates. N ¹- and N ⁹-alkyl-6(7)-Br-2,3-dihydroimidazo[1,2- a ]benzimidazoles can also be obtained by N -alkylation of 6(7)-Br-2,3-dihydroimidazo[1,2- a ]benzimidazoles under neutral or basic conditions.

A new method was proposed for the preparation of 5-amino-3-(cyanomethyl)-1 H -pyrazole-4-carbonitrile by reacting the potassium salt of malononitrile dimer with hydrazinium sulfate. The reaction of 5-amino-3(cyanomethyl)-1 H -pyrazole-4-carbonitrile with aromatic aldehydes in the presence of catalytic amounts of morpholine leads to the formation of Knoevenagel condensation products. Aminomethylation of the resulting ( Z )-5amino-3-(2-aryl-1-cyanovinyl)-1 H -pyrazole-4-carbonitriles with primary aromatic amines and excess aqueous HCHO in refluxing DMF leads to the formation of 7-(2-aryl-1-cyanovinyl)-1,2,3,4-tetrahydropyrazolo[1,5- a ][1,3,5]triazine-8-carbonitriles. Bioavailability parameters were studied in silico , and possible protein targets were predicted by protein-ligand docking. In an in vitro experiment on cultures of E. coli , S. aureus and B. pumilis , 5-amino-3-(cyanomethyl)-1 H -pyrazole-4-carbonitrile does not show any noticeable antibacterial effect. At the same time, three compounds of the pyrazolo[1,5- a ][1,3,5]triazine series showed a pronounced antidote effect against the herbicide 2,4-D on sunflower seedlings in a laboratory experiment, for one compound a noticeable growth-stimulating effect was noted.

A new variation of the sila-Sonogashira reaction was proposed, which involves the use of tetraalkynylsilane as an alkynylating reagent. It was found that the reaction proceeds most efficiently at an equivalent ratio of tetraalkynylsilane and iodoarene catalyzed by 5 mol% Pd(PPh₃)₂Cl₂ and 10% CuI in the presence of 10-fold amount of triethylamine in chloroform. The title tolanes yields are 58-85%.

A series of S -methylated derivatives of 2-thiouracil were prepared and then phosphonylated with diethyl chlorophosphate. The reaction conditions were optimized, the structure of the obtained compounds was determined by ¹Н, ¹³С, ³¹Р NMR spectroscopy methods.

A biocompatible supramolecular system based on sodium alginate and viologen calix[4]resorcinol for encapsulation of doxorubicin hydrochloride (DOX) was obtained. Using a set of physicochemical methods, the polymer- macrocycle ratio was found, at which stable nanoparticles are formed, and their morphological characteristics were determined. It was shown that with an increase in the concentration of calix[4]resorcinol, the size of nanoparticles increases and the zeta potential changes from negative to positive values. It was established that the most optimal supramolecular system for DOX binding is a composition with a macrocycle-polymer ratio of 1:50, and a change in the ratio of components can initiate drug release. The effect of encapsulated DOX on the physicochemical and biological properties of the supramolecular system was shown.

In four stages, by o -alkylation of phenol with 1-bromooctane, alkylation of octyloxybenzene with carbon tetrachloride, alkylation of phenol with tris(4-octyloxyphenyl)methanol, and nucleophilic substitution of the nitro group in 4-nitrophthalonitrile with tris(4-octyloxyphenyl)- 4-hydroxyphenylmethane, 4-{4-[tris(4-octyloxyphenyl)methyl]phenoxy}phthalonitrile was synthesized. Its reactions with copper(II), nickel(II), and cobalt(II) acetates in the presence of urea gave the corresponding metal phthalocyanines. The spectral properties of the obtained compounds were studied. All the phthalocyanines are not associated in chloroform at concentrations up to ~4×10^-5 mol/L. They do not exhibit mesomorphic properties, but upon cooling after heating, the copper and nickel complexes pass into a glass state.

In order to study the physicochemical and biological properties of the coordination compounds of bioactive metal ions with 2-hydroxyphenylphosphonic acid derivatives, the reaction of 2-hydroxy-5-ethylphenylphosphonic acid (Н₃L¹) with copper(II) perchlorate, sulfate, nitrate, and acetate in water was studied for the first time. It has been established that, regardless of the ratio of reagents, in the case of copper(II) perchlorate, sulfate, and nitrate, a complex of the composition [Cu(H₂L¹)₂(Н₂О)₂] is formed in high yield, while in the case of using copper(II) acetate a complex [Cu(HL¹)(H₂O)₂] is formed, the composition of which is established on the basis of a combination of elemental analysis data, IR and electronic spectra. Quantum-chemical calculations of the structure of [Cu(H₂L¹)₂(H₂O)₂] and [Cu(HL¹)(H₂O)₂] complexes were performed for the first time by the density functional theory (DFT) method. The cytotoxic properties of H₃L¹ acid and copper complexes [Cu(HL¹)(H₂O)₂] and [Cu(H₂L¹)₂(H₂O)₂] with respect to HeLa tumor cells of human cervical adenocarcinoma were studied. The accumulation of the resulting copper(II) complexes in HeLa cells was proved by laser confocal microscopy.