Novosibirsk Institute of Organic Chemistry

A series of novel hybrids of dehydroabietic acid (DHA) with semi-, thiosemicarbazides, and amino-1,3,4-oxadiazoles was synthesized starting from respective thioisocyanates or isocyanates. The cyclodehydrosulfurization of thiosemicarbazides with Hg(OAc)2 was used as a fast and efficient method to obtain regioisomeric 2-alkyl(aralkyl, aryl)amino-5-terpenyl- and 2-terpenylamino-5-alkyl(aralkyl, aryl)-1,3,4-oxadiazoles, even in the case of sterically hindered dehydroabietyl derivatives. Several conformationally flexible acylthiosemicarbazide and 2-amino-1,3,4-oxadiazole hybrids exhibited cytotoxicity against HepG2, MCF-7, and HeLa tumor cell lines that was significantly superior to that of the parent DHA. Among them, 2-(abieta-8,11,13-trien-18-oyl)-N-phenylhydrazincarbothioamide was the most active (GI50 = 12-17 µM), inhibiting the growth of tumor cells with greater selectivity (SI = 4.6-7.2) than doxorubicin, a positive control. The thiosemicarbazide moiety in the molecules of the acylthiosemicarbazide hybrids was important for the inhibition of the tumor cells' growth, while its adjacement mode to the terpenyl fragment was tolerant for retaining cytotoxicity. Replacement of the sulfur-containing thiosemicarbazide moiety with the sulfur-free semicarbazide resulted in the loss of cytotoxic properties. Absorption, distribution, metabolism, and excretion (ADME) parameters of the synthesized hybrids were assessed in silico.

Light-responsive molecules that can release drugs upon light absorption have attracted significant interest in chemistry and biology. BODIPY-based photoremovable protecting groups, or photocages, have recently emerged as especially promising tools in this respect. However, the exact photorelease mechanism is still not fully understood. We study the photochemical decomposition of meso-Methyl-BODIPY-conjugated epinephrine using 1H nuclear magnetic resonance and chemically induced dynamic nuclear polarization (CIDNP) techniques. After irradiation, epinephrine was detected only in trace amounts, whereas its oxidation product, adrenochrome, was the predominant product. Surprisingly, the CIDNP study has shown that the electron transfer (ET) in this reaction does not proceed from epinephrine to the BODIPY moiety, but rather occurs between two BODIPY cores. To validate this hypothesis, we applied the CIDNP method to detect photoinduced ET between two model BODIPY molecules in solution. In addition, the radical cation of BODIPY has been detected for the first time by CIDNP under photolysis in the presence of the electron acceptor-chloranil. The hyperfine interaction (HFI) constants of the BODIPY radical cation were estimated from the CIDNP spectrum, and they are in agreement with the HFI constant predicted by density functional theory calculations. Due to high enhancement coefficients, the CIDNP technique allows for to detection of polarized BODIPY products at very low concentrations.

The first example of a metal-organic framework containing 4,7-di((–)-borneol)-1,10-phenanthroline (L) is prepared. The [Tb2(L)2Cl2(chdc)2]·8DMF·H2O (1) and [Tb2(L)2Cl2(chdc)2]·4DMA·2.115H2O (2) (chdc2– = = trans-1,4-cyclohexanedicarboxylate, DMF = N,N-dimethylformamide, DMA = N,N-dimethylacetamide) compounds are structurally characterized. Compound 1 crystallizes in the $P\bar{1}$ chiral space group. Both MOFs have a similar structure of coordination layers with the sql topology, but different 3D packing of the layers. The volume fraction available for the solvent in the pores of 1 and 2 is 27% and 33%, respectively.

We report the synthesis and characterization of two new rhenium(I) complexes [ReBr(CO)3(L)] (1) and [Re(CO)3(L)(m-XylylNC)]OTf (2), where m-XylylNC is 2,6-dimethylphenylisocyanide. These compounds are derived from the dipyrido[3,2-a:2′,3′-c]phenazine ligand functionalized with borneol group at the second position (m-XylylNC = 2,6-dimethylphenyl isocyanide). As determined by single crystal X-ray diffraction, the molecular structure of the 2 cation has a distorted octahedral geometry at the rhenium center coordinated by N,N′-chelating ligand L, one isonitryl and three carbonyl ligands.

The results of studying the low-energy secondary electronic spectra of fluorine-substituted furan‒phenylene co-oligomer films in the energy range from 5 to 20 eV above EF are reported. Thermal vacuum deposition of films with a thickness of 8–10 nm was performed on the surface of silicon substrates and layer-by-layer deposited ZnO. The energy position of the main peaks of the density of electronic states in the conduction band of the investigated films and the properties of the potential barrier between the films and substrate surfaces was determined. The surface topography of the thin films of the fluorine-substituted furan‒phenylene co-oligomer was studied by atomic force microscopy. The films on the ZnO surface have a granular structure with a grain diameter of ~100 nm in the surface plane. Grains on the (SiO2)n-Si surface have an elongated shape, characteristic of microwhiskers.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a key enzyme for the repair of stalled topoisomerase 1 (TOP1)-DNA complexes. Previously, we obtained HEK293A cells with homozygous knockout of the TDP1 gene by the CRISPR/Cas9 method and used them as a cell model to study the mechanisms of anticancer therapy and to investigate the effect of TDP1 gene knockout on gene expression changes in the human HEK293A cell line by transcriptome analysis. In this study, we investigated the effect of a TDP1 inhibitor ((R,E)-2-acetyl-6-(2-(2-(4-bromobenzyliden) hydrazinyl) thiazol-4-yl)-3,7,9-trihydroxy-8,9b-dimethyldibenzo[b,d] furan-1(9bH)-one, OL9-119, an usnic acid derivative), capable of potentiating the antitumor effect of topotecan, as well as its combination with topotecan, on the transcriptome of wild-type and TDP1 knockout HEK293A cells. OL9-119 was found to be able to reduce cell motility by decreasing the expression of a number of genes, which may explain the antimetastatic effect of this compound. Differentially expressed genes (DEGs) related to electron transport, mitochondrial function, and protein folding were also identified under TDP1 inhibitor treatment.