PROPELLANS – PERSPECTIVE FRAME COMPOUNDS FOR THE CREATION OF HIGH-ENERGY SUBSTANCES

Важной задачей современной органической химии является открытие новых, ранее не известных науке веществ, которые могли бы расширить область наших знаний и пополнить номенклатуру высокоэнергетических или биологически активных продуктов. 3,7,10-Триоксо-2,4,6,8,9,11-гексааза[3.3.3|пропеллан и его нитропроизводные являются новейшими продуктами класса гетероциклов, их азотсодержащая полициклическая структура предполагает наличие интересных и полезных свойств, что обусловливает проявленный интерес к данной работе. Химия 3,7,10-триоксо-2,4,6,8,9,11-гексааза[3.3.3|пропеллана малоизучена и представлена лишь двумя алкилпроизводными и теоретическими расчетами энергетических характеристик нитропроизводных. В статье преставлены результаты исследования нитрования 3,7,10-триоксо-2,4,6,8,9,11-гексааза[3.3.3]пропеллана (THAP) концентрированнойазотной кислотой. Установлено, что в процессе нитрования наблюдается протекание двух конкурирующих реакций – лактам-лактимной перегруппировки и нитрования. Было показано, что продукты реакции сильно зависят от температуры реакционной массы. Установлено, что температуре -40 ºС протекает образование лактимной формы ТНАР, тогда как при постепенном увеличении температуры сначала образуется мононитропроизводное пропеллана, а при температуре 40 ºС идёт селективное образование 3,7,10-триоксо-2,6-динитро-2,4,6,8,9,11-гексааза[3.3.3]пропеллана с выходом 30%. An important task of modern organic chemistry is the discovery of new substances previously unknown to science, which could expand the area of our knowledge and replenish the range of high-energy or biologically active products. 3,7,10-Trioxo-2,4,6,8,9,11-hexaaza[3.3.3]propellane and its nitro derivatives are the newest products of the class of heterocycles; interest in this work. The chemistry of 3,7,10-trioxo-2,4,6,8,9,11-hexaaza[3.3.3]propellane is poorly understood and is represented by only two alkyl derivatives and theoretical calculations of the energy characteristics of nitro derivatives. The article presents the results of a study of the nitration of 3,7,10-trioxo-2,4,6,8,9,11-hexaaza[3.3.3]propellane (THAP) with concentrated nitric acid. It was found that in the process of nitration, there are two competing reactions - lactam-lactam rearrangement and nitration. It was shown that the reaction products strongly depend on the temperature of the reaction mixture. It was found that at a temperature of -40 ºС the formation of the lactimic form of THAP proceeds, whereas with a gradual increase in temperature, a mononitro derivative of propellane is first formed, and at a temperature of 40 ºС, the selective formation of 3,7,10-trioxo-2,6-dinitro-2,4,6,8,9,11-hexaaza[3.3.3]propellane in 30% yield.

Study of the Biological Activity of Alkyl Derivatives of Tetrahydroisoquinolines

A row of 1-alkyne (C6-C17) derivatives against tetrahydroisoquinoline have been synthesized. 1-alkyne (C6-C17) derivatives cytotoxicity against three lines of cancer cells and two lines of normal cells was studied. It was found that 1-tridecyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline exhibits a high cytotoxic effect with low toxicity to healthy cells. Antimicrobial activity of 1-alkyne (C6-C17) derivatives against 5 strains of bacteria and fungus was studied. It has been found that 1-nonyl-6,7-dimethoxy-1,3,4-tetrahydroisoquinoline exhibits strong antibacterial and antifungal effects.

The Specificity and Broad Multitarget Properties of Ligands for the Free Fatty Acid Receptors FFA3/GPR41 and FFA2/GPR43 and the Related Hydroxycarboxylic Acid Receptor HCA2/GPR109A

The paradigm of ligand-receptor interactions postulated as “one compound—one target” has been evolving; a multi-target, pleiotropic approach is now considered to be realistic. Novel series of 1,4,5,6,7,8-hexahydro-5-oxoquinolines, pyranopyrimidines and S-alkyl derivatives of pyranopyrimidines have been synthesized in order to characterise their pleiotropic, multitarget activity on the FFA3/GPR41, FFA2/GPR43, and HCA2/GPR109A receptors. Hexahydroquinoline derivatives have been known to exhibit characteristic activity as FFA3/GPR41 ligands, but during this study we observed their impact on FFA2/GPR43 and HCA2/GPR109A receptors as well as their electron-donating activity. Oxopyranopyrimidine and thioxopyranopyrimidine type compounds have been studied as ligands of the HCA2/GPR109A receptor; nevertheless, they exhibited equal or higher activity towards FFA3/GPR41 and FFA2/GPR43 receptors. S-Alkyl derivatives of pyranopyrimidines that have not yet been studied as ligands of GPCRs were more active towards HCA2/GPR109A and FFA3/GPR41 receptors than towards FFA2/GPR43. Representative compounds from each synthesized series were able to decrease the lipopolysaccharide-induced gene expression and secretion of proinflammatory cytokines (IL-6, TNF-α) and of a chemokine (MCP-1) in THP-1 macrophages, resembling the effect of HCA2/GPR109A ligand niacin and the endogenous ligand propionate. This study revealed groups of compounds possessing multitarget activity towards several receptors. The obtained data could be useful for further development of multitarget ligands.

Antiadhesive Properties of Imidazolium Ionic Liquids Based on (−)-Menthol against Candida spp.

Infections with Candida spp. are commonly found in long-time denture wearers, and when under immunosuppression can lead to stomatitis. Imidazolium ionic liquids with an alkyl or alkyloxymethyl chain and a natural (1R,2S,5R)-(−)-menthol substituent possess high antifungal and antiadhesive properties towards C. albicans, C. parapsilosis, C. glabrata and C. krusei. We tested three compounds and found they disturbed fungal plasma membranes, with no significant hemolytic properties. In the smallest hemolytic concentrations, all compounds inhibited C. albicans biofilm formation on acrylic, and partially on porcelain and alloy dentures. Biofilm eradication may result from hyphae inhibition (for alkyl derivatives) or cell wall lysis and reduction of adhesins level (for alkyloxymethyl derivative). Thus, we propose the compounds presented herein as potential anti-fungal denture cleaners or denture fixatives, especially due to their low toxicity towards mammalian erythrocytes after short-term exposure.

Investigation of physical and chemical properties of new derivatives of 5-(thiophene-3-ylmethyl)-4R-1,2,4-triazole-3-thiols

Heterocyclic compounds are one of the most important branches of modern organic chemistry and are widely used in medicine, pharmacy, agriculture, and in the production of new materials. One of these compounds is 1,2,4-triazole, which has attracted the attention of scientists around the world for many years. The aim of the work is to synthesize new derivatives of 5-(thiophene-3-ylmethyl)-4R-1,2,4-triazole-3-thiols and study their physical-chemical properties, conducting primary pharmacological screening. Materials and methods. Organic synthesis classical methods were used in the study, as well as a complex of physical-chemical analysis methods (1H NMR spectroscopy, elemental analysis, Elisa and chromato-mass spectral studies) were done. Prediction of pharmacological activity was carried out by using the PASS online computer program. Results. Two initial compounds were obtained: 5-(thiophene-3-ylmethyl)-4phenyl-1,2,4-triazole-3-thiol and 5-(thiophene-3-ylmethyl)-4H-1,2,4-triazole-3-thiol. During their further chemical transformation, a number of new corresponding alkyl derivatives were obtained. The structure of the synthesized compounds was confirmed using modern physical-chemical methods of analysis. Based on the results of pharmacological screening, the high activity of the obtained compounds can be predicted. Conclusions. 5-(thiophene-3-ylmethyl)-4H-1,2,4-triazole-3-thiol, 5-(thiophene-3-ylmethyl)-4-phenyl-1,2,4-triazole-3-thiol and a number of their alkyl derivatives were synthesized. The structure and individuality were proved thanks to modern physical and chemical methods of analysis. Having analyzed the results of primary pharmacological screening of a number of obtained compounds, some of them were selected for further study.

Regioselective Mercury(I)/Palladium(II)-Catalyzed Single-Step Approach for the Synthesis of Imines and 2-Substituted Indoles

An efficient synthesis of ketimines was achieved through a regioselective Hg(I)-catalyzed hydroamination of terminal acetylenes in the presence of anilines. The Pd(II)-catalyzed cyclization of these imines into the 2-substituted indoles was satisfactorily carried out by a C-H activation. In a single-step approach, a variety of 2-substituted indoles were also generated via a Hg(I)/Pd(II)-catalyzed, one-pot, two-step process, starting from anilines and terminal acetylenes. The arylacetylenes proved to be more effective than the alkyl derivatives.

Effect of alkyl derivatization of gellan gum during the fabrication of electrospun membranes

Electrospun nanofibers based on polysaccharides represent a consolidated approach in Tissue Engineering and Regenerative Medicine (TERM) and nanomedicine as a drug delivery system (DDS). In this work, two chemical derivatives of a low molecular weight gellan gum (96.7 kDa) with aliphatic pendant tails were processed by electrospinning technique into non-woven nanofibrous mats. In order to generate spinnable blends, it was necessary to associate poly vinyl alcohol (PVA). The relationships between the physicochemical properties and the processability via electrospinning technique of gellan gum alkyl derivatives (GG-C8 and GG-C12 having a degree of alkyl chain derivatization of 17 mol % and 18 mol %, respectively) were investigated. The deposition of nanometric fibers (212.4 nm ± 60.0) was achieved by using the blend GG-C8/PVA spinned at 5% w/v in water. The use of a binary solvent composed of water and ethanol in a volumetric ratio 95:5 improved further spinnability obtaining similar nanofiber diameters (218.0 nm ± 96.0). The rheological analysis has allowed to highlight the role of the alkyl portion (C8 and C12) on the spinnability of the blended polymers.

Synthesis of alkyl derivatives of 3,7,10-trioxo-2,4,6,8,9,11-hexaaza[3.3.3]propellane and evaluation of their biological activity

Today 3,7,10-trioxo-2,4,6,8,9,11-hexaaaza[3.3.3]propellane (THAP) has not yet received widespread re-search attention due to the complexity of the synthesis. This work is devoted to the development of a method for the THAP derivatives synthesis, as well as to the study of their biological activity in comparison with al-kyl-substituted glycolurils (subject of comparison). ТНАРwas N-alkylated to furnish novel hexaalkyl deriva-tives of ТНАРwith methyl, ethyl and propyl substituents. The conditionsfor obtaining the maximum yield of the target productwere optimizedon the base of methyl derivative. The reaction proceeded in DMSO/КОНat 75–80ºC for 13hours in a moderate yield of 56%. The ethyl and propyl derivatives of ТНАРwere synthe-sized under the same conditions. The biological activity of the obtained ТНАРalkyl derivatives and glycoluril alkyl derivatives was evaluated against Sporosarcina ureae, Bacillus pumilus, Salmonella typhimurium and Staphylococcus aureus bacteria and influenza A virus. All the samples were found to exhib-it antibacterial activity against Staphylococcus aureus.It was shown that 2,4,6,8,9,11-hexapropyl-ТНАР, di-tert-butyl-diphenyl-, di-tert-butyl-dibenzyl-, di-tert-butyl-dimethyl-and di-isopropyl-dibenzylglycoluril, have exhibited also toxicity to living cells besides antiviral activity