We report here the synthesis of mixed salts of cobalt (II) with α-ketocarboxylic and mercaptocarboxylic acids, which have different types of antidote activity, in a single molecule. Simultaneous administration of the mixed cobalt salt with poison (sodium cyanide) at doses corresponding to the LD50 and LD99 ameliorated the main symptoms of poisoning by 75 – 100% and prevented death. The index of protection (IP) and antidote power (AP) on intragastric administration of compound 1a at a dose of 300 mg/kg immediately after sodium cyanide poisoning were 1.40 and 1.08 respectively. Prophylactic administration 30 min before poison increased these values 1.8-fold, giving IP = 2.5 and AP = 1.9.

The mercury test is a rapid and widely used method for distinguishing truly homogeneous molecular catalysis from nanoparticle metal catalysis. In the current work, using various M-0 and M-II complexes of palladium and platinum that are often used in homogeneous catalysis as examples, we demonstrated that the mercury test is generally inadequate as a method for distinguishing between homogeneous and cluster/nanoparticle catalysis mechanisms for the following reasons: (i) the general and facile reactivity of both molecular M-0 and M-II complexes toward metallic mercury and (ii) the very high and often unpredictable dependence of the test results on the operational conditions and the inability to develop universal quantitatively defined operational parameter Two main types or mercury-induced transformations, the cleavage of M-0 complexes and the oxidative-reductive transmetalation of M-II complexes, including a reaction of highly popular M-II/NHC comp(l)exes, were elucidated using NMR, ESI-MS, and EDXRF techniques. A mechanistic picture of the reactions involving metal complexes was revealed with mercury, and representative metal species were isolated and characterized. Even in an attempt to not overstate the results, one must note that the use of the mercury tests often leads to inaccurate conclusions and complicates the mechanistic studies of these catalytic systems. As a general concept, distinguishing reaction mechanisms (homogeneous vs cluster/nanoparticle) by using catalyst poisoning requires careful rethinking in the case of dynamic catalytic systems.

New gelling agents have been discovered: glycoluril carboxylic acid amides, giving two-component gels with imidazole. First, the one-pot, two step reaction of glycoluril carboxylic acids, CDI and various amines was investigated for the preparation of gels and it was found that the reaction mixtures were gelled in dry DMF during the preparation of some amides. The conditions of the gel-sol-gel transitions were found. The morphology of the xerogels was studied by SEM. The structure of the xerogels is constructed from interlocked rods or from interlaced curved fibres. Self-organization in the co-crystals of amides with H2O or imidazole was detected. The molecules of the co-crystals of amides with H2O are self-assembled into homochiral tapes. (C) 2019 Elsevier Ltd. All rights reserved.

A spectrum of differentially expressed microRNAs was determined by the massively parallel sequencing method in normal healthy prostate tissues, in hormone-dependent prostate cancer samples, and in the LNCaP and DU145 cell lines. A set of microRNAs in tumors and prostate cancer (PCa) cell lines was identified on the basis of the changes in expression compared with that in normal prostate tissues. Twenty-seven aberrantly expressed microRNAs were detected in tumor tissues and ten of them showed significant changes in expression in LNCaP and DU145 cells. Seven of them demonstrated the change of the expression in the same direction in all the tumor samples as well as in the PCa cell lines. The expression of miR-148a changed in DU145 cells in the opposite direction compared with that in LNCaP cells and tumors. The expression of let-7c, let-7b, miR-99a, miR-125b-2, miR-100, miR-10a, and miR-31 was reversed in DU145 cells compared with LNCaP cells. However, these microRNAs exhibited no significant changes in expression in tumors. It turns out that the target of miR-148a, let-7b, and microRNAs, included in the miR-99a/let-7c/miR-125b-2 cluster, the expression of which increased in LNCaP cells and decreased in DU145 cells, is the insulin-like growth factor receptor gene 1 (IGF1R). The obtained data make it possible to assume that the differences in the effect of microRNAs in cell lines are connected with their repressive influence on IGF1R expression in hormone-sensitive LNCaP cells and an absence of such influence in the hormone-independent DU145 cell line.

A new method for the synthesis of complexes PtIV(NHC)X4L (NHC is N-heterocyclic carbene of imidazole or benzimidazole series; X = Cl, Br; L is N-coordinated pyridine or NHC) based on mechanochemical oxidation of complexes PtII(NHC)X2L with dichloroiodobenzene (PhICl2) or pyridinium hydrobromide perbromide (PyHBr3) was proposed. Mechanochemical activation led to reduction in the synthesis time and increase in the selectivity of halogenation and yields of the target PtIV complexes (74–98%) as compared to the reaction in solutions.

We studied microRNA gene expression in HeLa cells following exposure for 6 h and 8 days to Co60 gamma rays at a dose of 4 Gy using an approach of large-scale parallel DNA sequencing. We identified 12 microRNAs with aberrant expression which were maintained in cell generations. The analysis of radiation-induced aberrant expression of pre-microRNAs made it possible to assess the importance of nuclear and cytoplasmic stages of microRNA biogenesis for preservation of its aberrant expression. On cell treatment by 5-azacytidine, aberrant expression was maintained only in two microRNAs: miR-21-3p and miR-422a, which demonstrated an increase in expression. Radiation-induced decrease in expression in ten examined microRNAs was dependent on DNA demethylation. At the same time, expression in a microRNA set, which demonstrated inheritable alteration of the expression after gamma-radiation exposure in the untreated cells, was not dependent or was weakly dependent on DNA methylation. The obtained results suggest that ionizing radiation induces aberrant DNA methylation, which affects inherited expression changes in microRNAs in cell generations after exposure to the mutagen.

It was first shown that DNA damage induction in mitomycin C-treated HeLa cells leads to a change in the selection of 5p and 3p microRNA duplex strands in the formation of the RNA-induced silencing complex (RISC).

Coupling of 6-(carboxy)alkyl-2,4-dialkylglycolurils with N-(hydroxymethyl)glycolurils gives N,N’-methylenebisglycolurils totally substituted at the nitrogen atoms, which are formed mostly as racemate diastereomers.

Впервые показано, что индукция повреждений ДНК при обработке клеток HeLa митомицином C приводит к изменению селекции нитей 5р и 3р дуплекса микроРНК при формировании комплекса RISC (RNA-induced silencing complex).

The dependence of expression of miRNAs and their precursors (pre-miRNAs) on the DNA methylation level in HeLa cells 8 days after mitomycin C treatment was studied. A massive parallel DNA sequencing method was applied to analyze miRNA expression. 5-Azacytidine (DNA methylation inhibitor) was added to the medium 6 days after mutagenic agent exposure. The results indicated that the change in expression for some mature miRNAs (39 of 61) was accompanied by the change in the expression of their pre-miRNAs, while there were no significant changes in the expression of pre-miRNA for other mature miRNAs (22 of 61). The aberrant expression was maintained by 8 of 61 mature miRNAs and 6 of 55 pre-miRNAs in the induced HeLa cells after 5-azacytidine treatment. In addition, the expression of more than 90% of miRNAs, which indicated a significant change in expression after mitomycin C treatment, does not depend or depends slightly on the DNA methylation level in HeLa cells without mitomycin C treatment. The results suggest that mitomycin C induces aberrant DNA methylation which affects maintenance of changes in the miRNA expression in cell generations after mutagen treatment.

This work is devoted to the study and obtaining of new radioprotective agents based on natural flavonoid genistein and spherical amorphous nanoparticles (SANPs) produced from a mixture of birch bark triterpenoids. The physicochemical characteristics of the nanoparticles were studied by electron microscopy, dynamic light scattering, and UV-VIS spectroscopy. The radioprotective efficacy of the nanodrug in vivo and the possibility of its use as a radioprotective agent was shown.

The condensation of aliphatic alkylamines and achiral amino acids with 1,5-butano-2,4,6,8-tetra-(hydroxymethyl)- and 2,4,6,8-tetra(hydroxymethyl)glycolurils was used to prepare and characterize polycyclic condensed compounds (including some previously unknown examples) containing glycoluril and alkylamine fragments. X-ray structural study of the obtained compounds was used to identify n(N)→σ(C–H) anomeric interaction.

Regioselective reactions of N -(carboxyalkyl)ureas (ureido acids) and N -(aminoethyl)ureas with 1,2-dioxo-1,2-diphenylethane (benzyl) and glyoxal are studied in detail. The structure of the reactants affects the reaction regioselectivity. Acid-catalyzed reactions of glyoxal with 1-[2-(dimethylamino(acetylamino))ethyl]ureas and benzene with ureido acids result mainly in 2,6-di-substituted glycolurils. The structure of 2,6-di(methoxycarbonylethyl)glycoluril is unambiguously established by X-ray diffraction.