Grabovskiy, Stanislav A

Grabovskii S.A., Andriyashina N.M., Lobov A.N., Safiullin R.L.

Abstract: 5-amino-3-hydroxy-1-phenyl-1H-pyrazol and 3-amino-5-hydroxy-1-phenyl-1H-pyrazol are widely used as synthons in organic and pharmaceutical chemistry. We developed a high-yield synthesis method for 5-amino-3-hydroxy-1-phenyl-1H-pyrazol using high-pressure and base catalysis, achieving up to 80% yield. This method significantly outperforms existing techniques, which yield no more than 39%. The synthesis was performed at pressures up to 10 katm, both in solvent-free conditions and in the presence of solvents, such as methanol, ethanol, toluene, tert-butyl methyl ether, and 1,4-dioxane. Thermodynamic parameters of possible paths were calculated using the SMD-M06- 2X/MG3S method. Applying high pressure (7 katm) enables the solvent-free and catalyst-free synthesis of 2-cyano-N'-phenylacetohydrazide with a yield of 96%. This compound can subsequently be converted into 5-amino-3-hydroxy-1-phenyl-1H-pyrazol with yields of up to 90% using base catalysis. Additionally, the reaction pathways of phenylhydrazine with ethyl cyanoacetate and its anion have been explored. These pathways are discussed in terms of thermodynamic potentials calculated using the SMD-M06-2X/MG3S method. High pressure significantly accelerates the reaction between phenylhydrazine and ethyl cyanoacetate, leading to the formation of 2-cyano-N'-phenylacetohydrazide. This intermediate can then be easily converted into 5-amino-3-hydroxy-1-phenyl-1H-pyrazol. Under neutral conditions, the most favorable reaction pathway involves the attack of the terminal nitrogen of phenylhydrazine on the carbonyl group. In the case of the ethyl cyanoacetate anion, the attack also targets the carbonyl group, but occurs via the phenyl-substituted nitrogen.

Egorov V., Valiullin L., Raginov I., Grabovskiy S., Gafiyatov R., Artemenko A., Zakharenko A., Golokhvast K.

In order to study the effect of a number of 6-substituted uracil derivatives on bovine embryo lung cells, experiments were conducted. According to the study, the effect of the studied substances on the cultural and morphological properties of cell was determined by taking into account their viability and proliferation index. In %, it was calculated that viability was determined by the ratio of living cells to their total number. The proliferation index was determined as the ratio of the number of proliferating cells to the number of seeded cells. At 0.1 mM concentration of the compounds studied, a decrease in LEK cell viability was recorded compared to the control group, but this was only the case for compound No. 2. When other compounds were used at doses of 0.1 mM, LEK cell viability increased by 3.0-7.0% compared to controls. Increasing the dose of the compounds studied to 1.0 mM results in a 10.0% decrease in survival in the presence of compounds No. 3 and 6, 16.0% in the presence of compounds No. 2 and 7, 19.0% in the presence of compound No. 4 and 25.0% in the presence of compounds No. 8 and 9.

Golovanov A.A., Odin I.S., Gordon K.V., Itakhunov R.N., Gusev D.M., Sokov S.A., Vologzhanina A.V., Grabovskiy S.A., Sosnin I.M., Ukolov A.I., Orlova O.I., Lazarenko V.A., Dorovatovskii P.V., Darmoroz D.D., Piven A.O., et. al.

AbstractOn the basis of the selective reactions of hydrazines with trialkylsilyl-substituted cross-conjugated enynones (pent-1-en-4-yn-3-ones) as fundamental building blocks, this work presents the developed common methodology for the synthesis of polysubstituted luminescent derivatives of acetylenic pyrazolines, pyrazoles, and combined polyheterocycles containing structural fragments from pyrazolines, isoxazoles, thiophenes, thiazoles, benzo[d]thiazoles, and benzo[d]imidazoles. In reactions with hydrazine and its monosubstituted aromatic and heteroaromatic derivatives, the mentioned pent-1-en-4-yn-3-ones, containing Me3Si, Et3Si, and t-BuMe2Si groups at the triple bond, give 3-(trialkylsilyl)ethynylpyrazolines. Following stages of desilylation and 1,3-dipolar cycloaddition with nitrile oxides, the 3-(trialkylsilyl)ethynylpyrazolines provide the formation of combined polyheterocyclic derivatives. Thus, a one-pot synthetic route to pyrazoline-containing isoxazoles from cross-conjugated enynones, arylhydrazines, and α-chlorobenzaldoximes has been developed. Some aspects of cyclocondensation mechanism and luminescent properties of synthesized azoles derivatives were examined.

Baeva L.A., Grabovskiy S.A., Biktasheva L.F., Safiullin R.L.

Oxidation of 4-[(alkylsulfanyl)methyl]-3,5-dimethylisoxazoles with 1,1-di(hydroperoxy)-cyclohexane in benzene or ethanol under mild conditions gave the corresponding 4-[(alkyl-sulfinyl)methyl]-3,5-dimethylisoxazoles in up to 99% yields.

Gallyamova R.F., Grabovskiy S.A., Dokichev V.A., Musin F.F.

Surface modification of carbon fiber with 1,1-dihydroperoxycyclohexane (DHPC) before application of SiO2 barrier coating was studied. IR spectroscopy showed presence of the COOH carboxyl groups on the surface of modified carbon fibers. The modified surface has less hydrophobicity due to the presence of polar groups, which contribute to a change in the wettability of the fiber by the sol–gel solution and the adhesion of the oxide coating to the fiber surface. The quality and thickness of the oxide coatings were assessed by scanning electron microscopy. The use of DHPC leads to oxidation of the carbon fiber, making surface longitudinal stripes deeper. To determine the effect of DHPC modification on the properties of the fiber surface, a SiO2 coating was applied by immersion in a tetraethoxysilane sol. DHPC modification leads to the formation of a uniform SiO2 coating on the fiber surface. After the heat treatment, the coating thickness on the DHPC–modified fibers is 130 ± 30 nm. Analysis of the IR spectra showed that the addition of DHPC to the sol leads to an increase in the intensity of the Si–O–Si, Si–OH, and OH absorption bands, which are characteristic of the hydrolysis and polycondensation products of tetraethoxysilane. In the wavenumber range of 400–1200 cm–1, the Si–O–Si fragments form, which is confirmed by the presence of bands of Si–O– deformation bond at ν = 881 and 442 cm–1. The introduction of DHPC into the sol promotes the formation of a uniform coating on the carbon fibers. The coating thickness on the initial fibers reaches 410±100 nm at room temperature, decreasing to 190±60 nm after heating. The fiber and sol modification contribute to formation of a uniform coating with a thickness of 200 ± 70 nm and 130 ± 30 nm before and after the heating, respectively. DHPC modification of the fiber surface and tetraethoxysilane sol promotes the formation of continuous, uniform, and quality SiO2 coatings on the surface of carbon fibers.

Andriyashina N.M., Grabovskii S.A., Safiullin R.L.

Background: 1,1-Bishydroperoxides are used as oxidizing agents, radical initiators, in addition, studies of biological activity show the promise of this area of research. Objective: There are currently no kinetic data on the thermal stability of these peroxides in various solvents. Therefore, we investigated the thermal stability of 1,1-dihydroperoxycyclohexane as the most widely used at present. Methods: The rate constants and activation parameters were measured at the temperature range of 100-170 C in the presence of 2-naphthol, which inhibits the induced decomposition of the peroxide by free radicals. Peroxide concentration was determined by iodometric method. Results: The rate constants of the reaction with the solvents and of the monomolecular decomposition of the peroxide were determined. Conclusion: The use of DHPC as a radical initiator requires taking into account its reactions with the solvent and/or monomer, in addition to its monomolecular decomposition with the formation of free radicals.

Grabovskii S.A., Andriyashina N.M., Lobov A.N., Antipin A.V., Safiullin R.L.

AbstractA facile and efficient method for the oxidation of sulfides (dialkyl, phenylalkyl, benzylalkyl) to sulfoxides under mild conditions without using any catalysts is reported. This method afforded a series of sulfoxides with good yields (>95%). The ready accessibility and low cost of the gem-dihydroperoxides will endow it with attractive applications in chemical synthesis as oxidants.

Golovanov A.A., Itakhunov R., Odin I.S., Gusev D., Grabovskiy S.A., Gordon K.V., Vologzhanina A.V., Sokov S., Sosnin I.M.

Condensation of 1,5-disubstituted pent-1-en-4-yn-1-ones with arylhydrazines in acidified alcohol results mainly in the formation of the corresponding arylhydrazones with traces of the side products of cyclization at the double bond - 1,5-diaryl-3-(arylethynyl)-4,5-dihydro-1H-pyrazoles (pyrazolines). Arylhydrazones are cyclized only by refluxing in high-boiling polar solvents (DMF and ethylene glycol), with the selective formation of 1,5-disubstituted 3-styrylpyrazoles in up to 77-95% yields. Thermodynamically, the cyclization of arylhydrazones at the triple bond is the most preferable pathway, as shown by DFT calculations and preparative synthesis experiments. Thus, we demonstrate that the reactions of arylhydrazines with 1,5-disubstituted pent-1-en-4-yn-1-ones lead to the formation of arylhydrazones and side pyrazoline impurities in a parallel (not consecutive) manner. 2-Hydrazinylpyridine interacts with 1,5-disubstituted pent-1-en-4-yn-1-ones in some other way, giving not pyridinylhydrazones but 2-(5-styryl-3-phenyl-1H-pyrazol-1-yl)pyridines (despite the acidity of the medium). The authors have developed a gram-scale synthesis method for these compounds, which were obtained in up to 60-82% yields. Besides, we have developed the synthesis method for certain styrylpyrazoles, which are quite promising substances for use as fluorescent probes. Their spectral-luminescence characteristics were examined as well as their complexing with Hg2+, Cd2+, and Pb2+ ions.

Grabovskiy S.A.

Low-temperature (–90°C) ozonolysis of tris(trimethylsilyl)silane gave tris(trimethylsilyl)silanol and 1,1,1-trimethyl-2,2-bis(trimethylsiloxy)disilan-2-ol. The primary isotope effect in the reaction of tris(trimethylsilyl)silane with ozone at –90°C is equal to 5.5 and is consistent with the theoretical value calculated at the B3LYP/6-31+G(2d,p) level of theory assuming abstraction of H(D) from the Si–H(D) bond by ozone. Possible reaction mechanisms, namely radical, ionic, and ozone insertion into the Si–H bond, are discussed.

Grabovskiy S.A., Kabal’nova N.N.

Oxidation of triethylsilane, tert-butyldimethylsilane, dimethylphenylsilane, triphenylsilane, 1,1,1,2tetramethyl-2-phenyldisilane, tris(trimethylsilyl)silane, hexamethyldisilane, tetrakis(trimethylsilyl)silane, 1,1,3,3tetraisopropyldisiloxane with chlorine dioxide was carried out. The reaction products of studied triorganosilanes with chlorine dioxide in an acetonitrile solution were the corresponding silanols and siloxanes. A mechanism explaining the formation of products and the observed regularities of the oxidation of silanes with chlorine dioxide has been proposed. A thermochemical analysis of some possible pathways in the gas phase using methods G4, G3, M05, and in an acetonitrile solution by the SMD-M05 method was carried out. The oxidation process can occur both with the participation of ionic and radical intermediates, depending on the structure of the oxidized substrate and medium.

Golovanov A.A., Odin I.S., Gusev D.M., Vologzhanina A.V., Sosnin I.M., Grabovskiy S.A.

The cyclocondensation of cross-conjugated enynones, dienynones, and trienynones (easily available due to low-cost starting compounds) with arylhydrazines leads to the regioselective synthesis of pyrazole derivatives (dihetaryl-substituted ethens, buta-1,3-diens, and hexa-1,3,5-triens) or results in 4,5-dihydro-1H-pyrazoles in good yield. The reaction path is controlled by the character of the substituent in enynone: the pyrazoles are obtained from the reaction of substrates that contain five-membered heteroaromatic substituents with arylhydrazines, and the 4,5-dihydro-1H-pyrazoles are obtained from the reaction of 1,5-diphenylpent-1-en-4-yn-3-one with arylhydrazines consistently. Despite the presence of a substituent, cyclocondensation of 2-hydrazinylpyridine with all of examined cross-conjugated enynones leads to the formation of pyrazoles. The reaction does not require special conditions (temperature, catalyst, inert atmosphere). The cyclocondensation pathways are determined by the electronic effect of an electron-rich five-membered heteroaromatic ring in the substrate. The synthesis allows use of various substituents and functional groups in enynone and hydrazine. The present method features high yields and simplicity of the product purification. The obtained pyrazoles possess fluorescent properties with a quantum yield up to 31%.

Grabovskiy S.A., Kabal’nova N.N., Andriayshina N.M., Egorov V.I., Valiullin L.R., Nabatov A.A., Raginov I.S., Murinov Y.I.

Context: Previously, we investigated the relationship between the nature of the substituent at the 5-position of the uracil ring and the action of the corresponding uracil derivatives on immortalized lung cells. In the present study, we analyzed the impact of some 6-substituted uracil-derivatives on the regeneration potential of the lung cells (LC). Aims: To evaluate uracil derivatives capable of stimulating lung cell proliferation to create drugs that accelerate lung regeneration. Methods: The level of cell proliferation, maximum tolerated dose, and toxic effect of 6-substituted uracil derivatives (9 compounds) were studied on the immortalized lung epithelial cells and compared with the known drug 6-methyluracil. Results: The maximum tolerated dose of compounds for the LC line depends on the chemical structure of the compounds. The highest level of cell proliferation and tolerated was demonstrated when was used 3-methyl-6-cyclopropyluracil and 1-butyl-6-methyluracil. Conclusions: 3-methyl-6-cyclopropyluracil and 1-butyl-6-methyluracil exhibit a high proliferative activity in vitro so they could be recommended for additional studies of regenerative activity in vivo.

Grabovskii S.A., Akchurin T.I., Dokichev V.A.

The results of studies over the past ten years in the field of C=C bond hydrogenation in the presence of palladium catalysts deposited on various inorganic and organic carriers such activated carbons, carbon nanotubes, alumina, zeolites, or composite materials based on Al₂O₃-SiO₂, polystyrene, polypropyleneimine, polyamidoamine and hybrid inorganic/ polymer-carriers, are presented. The selectivity and rates of the hydrogenation process are considered and some comparisons are made. Porous supports and containing dendrimers generally retain palladium particles more effectively. Nanosized palladium stabilized by different dendrimers catalyzes the hydrogenation of C=C bonds in polyfunctional compounds chemoselectively without affecting functional groups, such as CHO, C=O, C(O)OR, CN, NO2, and halogens.

Grabovskii S.A., Grabovskaya Y.S., Antipin A.V., Kabal’nova N.N.

The O–H bond strength was calculated by the G4 and the M06-2X/MG3S methods for 2‑hydroxy-3-methylcyclopent-2-en-1-one (maple lactone), 4-hydroxy-2,3-dimethyl-2H-furan-5-one (sotolon), 4-hydroxy-5-methylfuran-3-one, 4-hydroxy-2,5-dimethylfuran-3-one (strawberry furanone), (2R)-2-[(1S)-1,2-dihydroxyethyl]-3,4-dihydroxy-2H-furan-5-one (ascorbic acid), 5-hydroxy-2-(hydroxymethyl)pyran-4-one (kojic acid), 3-hydroxy-2-methylpyran-4-one (maltol), 3-hydroxy-2-ethylpyran-4-one (ethylmaltol), 4-hydroxy-6-methylpyran-2-one, and 5-hydroxy-6-methyl-3,4-dihydro-2H-pyran-4-one (dihydromaltol). The calculations indicated the presence of a weak O–H bond of less than 82.0 kcal/mol in 4-hydroxyfuran-3-one derivatives. The experimental rate constant of the reaction of the compound with the lowest O–H bond strength, 4-hydroxy-2,5-dimethylfuran-3-one, with peroxyl radicals in chlorobenzene and acetonitrile was comparable to the data for dibutylhydroxytoluene, but the stoichiometric coefficient of inhibition was 0.17 (PhCl) and 0.66 (MeCN), which was significantly smaller than for dibutylhydroxytoluene. The activation enthalpy for hydrogen atom elimination from 4-hydroxy-2,5-dimethylfuran-3-one by peroxyl radicals calculated by the SMD(PhCl)-M05/MG3S method correlated well with the data for 5-hydroxy and 5-aminouracil derivatives, which is indicative of the common mechanism of interaction of these compounds with peroxyl radicals.

Andriyashina N.M., Grabovsky S.A., Kabalnova N.N.

Thermal stability of cyclododecylidene-1,1-bishydroperoxide in xylene has been studied and activation parameters of the reaction have been determined. The thermolysis has been accompanied by the reaction with ferrocene and the induced radical chain decomposition of cyclododecylidene-1,1-bishydroperoxide.

Hemamalini A., Rajarathinam C., Paul A.W., Jothi A.I.

Wang S., Wang Y., Zha F., Tang X., Chang Y., Tian H.

Baimakhanova B., Sadanov A., Baimakhanova G., Tluebekova D., Amangeldi A., Turlybaeva Z., Ratnikova I., Nurgaliyeva Z., Seisebayeva R., Ussipbek B., Umbetyarova L., Amirkhanova A., Seitimova G., Turgumbayeva A.

Mentha asiatica Boriss., a species native to Central Asia, has garnered significant attention for its diverse phytochemical profile and antimicrobial potential. This review synthesizes current knowledge on the antimicrobial activities of M. asiatica, focusing on its essential oils and other bioactive constituents. The study contextualizes the importance of natural antimicrobials in the era of rising antibiotic resistance and highlights the plant’s traditional use in ethnomedicine. The main methodologies explored include gas chromatography–mass spectrometry (GC–MS) for phytochemical characterization and various in vitro assays to assess antimicrobial efficacy against bacterial and fungal pathogens. The essential oils of M. asiatica demonstrate a broad spectrum of activity, attributed to compounds such as menthol, menthone, and carvone. Other phytochemicals, including sesquiterpenes and terpenoids, also contribute to its bioactivity. The review underscores the potential of M. asiatica as a source of novel antimicrobial agents and calls for further research into its mechanisms of action, bioavailability, and safety profiles. The findings position M. asiatica as a promising candidate for developing plant-based antimicrobial formulations, addressing critical needs in healthcare and food preservation.

Petrova S.F., Khamitov E.M., Nugumanov T.R., Ivanov S.P.

Nayak R.R., Khairun H.S., Parveen G., Garg A., Chumachenko Y., Shu R., Gupta N.K.

AbstractThe circular economy and the depletion of Earth's resources highlight the need to transform waste into value‐added emerging materials like carbon quantum dots (CQDs), which show great promise in energy storage, catalysis, and other applications. The production of catalytically active CQDs from biomass garners significant attention due to their unique advantages, such as ease of availability, natural abundance, renewability, low cost, and environmental friendliness. This review addresses the synthesis of CQDs from biomass, the factors influencing their properties and performance, and their diverse applications in catalytic hydrogenation reactions, selective reduction of nitroaromatic compounds, and azo dyes. Recent studies demonstrate that biomass‐derived CQDs exhibit significantly improved catalytic activity, selectivity, and stability, effectively addressing the long‐standing challenges of low activity and poor stability in catalysts derived from conventional sources.

Kushwaha P., Bhardwaj A., Rashi, Khan D., Upadhyay A.

AbstractPhenylhydrazines, comprised of a phenyl group attached with hydrazine unit, contribute potentially to organic synthetic transformations. Because of the myriad of synthetic applications, the last decade has witnessed a considerable upsurge of interest to perform various reactions catalyzed/mediated/promoted by phenylhydrazines. Some of these reactions have shown high regioselectivity in short reaction time under mild reaction conditions. The emergence of innumerable synthetic transformations utilizing phenylhydrazine has unleashed numerous openings for the development of diverse heterocyclic scaffolds. Given the synthetic importance of this valuable chemical entity, this review highlights the methodologies utilizing phenylhydrazines. Moreover, the present article will contribute considerably to the organic synthesis as well as in pharmaceutical chemistry. Academically, this review article will be interesting and informative for the researchers attempting to develop new synthetic routes for the heterocyclic structures.

Stoykov I.I., Antipin I.S., Burilov V.A., Kurbangalieva A.R., Rostovsky N.V., Pankova A.S., Balova I.A., Remizov Y.O., Pevzner L.M., Petrov M.L., Vasily A.V., Averin A.D., Beletskaya I.P., Nenaydenko V.G., Beloglazkina E.K., et. al.

An overview of the main scientific achievements of Russian universities in the field of organic chemistry for the period 2018–2023 is presented.

Devi P., Yadav S., Pundeer R., Gupta S., Anand H., Choubey R.K., Kumar V., Gaur A., Kumar S.

A series of α-, β-unsaturated ketone derivatives of four substituted pyrazoles were synthesised using Claisen-Schmidt condensation reaction and were characterised using Fourier-transform infrared (FTIR) spectroscopy, 1H nuclear magnetic resonance (NMR) and 13C NMR spectroscopy. Further, these derivatives were studied under application as an oxidising agent in a compost-based microbial fuel cell (cMFC) to enhance its reduction efficiency. Characterisation methods of cyclic voltammetry (CV), linear sweep voltammetry (LSV), electrochemical impedance spectroscopy (EIS) and chrono-amperometry (CS) were employed to analyse the behaviour of the coin-cell device with and without pyrazoles at the cathode. Concentration dependence of the best pyrazole out of the series was studied to optimise the device performance. The results indicate the enhancement in bio-electro-catalytic activity and output power density when the cathode of the cMFC is laced with pyrazoles. In addition, sustainability and stability of the device was also investigated, and study to confirm the role of micro-organisms in the compost was also performed.

Karnakova S., Dvorko M., Shabalin D.

AbstractThis comprehensive review summarizes the published literature data concerning the chemistry of α‐enolizable alkynones, also denoted aliphatic or C−H active alkynones, where an alkyl group is adjacent to the carbonyl function, from the first example in 1949 to the present day. Starting from a historical perspective, the reader will be introduced to the recent achievements and future challenges in this field. The review covers around 100 references.

Gimadieva A.R., Khazimullina Y.Z., Gilimkhanova A.A., Mustafin A.G.

Nitrogen-containing heterocyclic compounds are widely used in pharmacology due to their pronounced biological activities and low toxicities. The introduction of a hydroxy function into uracil and pyridine molecules has led to compounds with antioxidant, anti-inflammatory, and immunomodulatory activity (3-hydroxy-6-methyl-2-ethylpyridine, 5-hydroxy-6-methyluracil, etc.). One of the successful methods for hydroxylation is peroxydisulfate oxidation. By modifying the Elbs reaction through catalysis and the introduction of additional oxidants, we have been able to significantly increase the yields of practically useful compounds.

Moussa Z., Ramanathan M., Alharmoozi S.M., Alkaabi S.A., Al Aryani S.H., Ahmed S.A., Al-Masri H.T.

Grabovskii S.A., Odin I.S., Golovanov A.A., Antipin A.V., Safiullin R.L.

The bond dissociation enthalpy of the N–H bond was calculated for the following compounds: 1-((E)-1,5-diphenylpent-1-en-4-yn-3-ylidene)-2-(o-tolyl)hydrazine, 1-((E)-1-(4-methoxyphenyl)-5-phenylpent-1-en-4-yn-3-ylidene)-2-phenylhydrazine, 1-((E)-1-phenylpent-1-en-4-yn-3-ylidene)-2-(p-tolyl)hydrazine, 1-((E)-1-(4-methoxyphenyl)-5-trimethylsilyl-1-en-4-yn-3-ylidene)-2-phenylhydrazine, and 1-((E)-1-(toiphenyl-2)-5-phenylpent-1-en-4-yn-3-ylidene)-2-phenylhydrazine. The calculations were performed by the M06-2X/6-311+G(2df,2pd)//B3LYP/6-31G(d) method using the homodesmotic approach. The bond dissociation enthalpy is lower than 77 kcal/mol for all the cross-conjugated hydrazone derivatives under study. The experimental rate constants for the reactions of the derivatives with peroxyl radicals in chlorobenzene during the initiated styrene oxidation are comparable to those of aromatic amines and are in the range (1.1–2.5) × 105 M−1 s−1. The stoichiometric inhibition coefficient depends on the structure of the derivatives and varies from 0.7 to 1.9. The inhibition is discussed within the framework of the radical mechanism.

Odin I.S., Itakhunov R.N., Gusev D.M., Vologzhanina A.V., Golovanov A.A.

5-(4,5-Dihydro-1H-pyrazol-3-yl)isoxazoles (pyrazoline-isoxazoles) are readily oxidized by active manganese dioxide in benzene or dichloromethane at room temperature. As a result, a simple and efficient method for the synthesis of the corresponding pyrazoleisoxazoles in 94–99% yields was developed. It was shown that 3-ethynyl-1H-pyrazoles are inactive in the 1,3-dipolar cycloaddition reaction with nitrile oxides and nitrile imines. The synthesized di- and trisubstituted pyrazole-isoxazoles showed weaker luminescent properties compared to pyrazoline-isoxazoles.

Kumar R., Sharma A., Sharma A.

Stoikov I.I., Antipin I.S., Burilov V.A., Kurbangalieva A.R., Rostovskii N.V., Pankova A.S., Balova I.A., Remizov Y.O., Pevzner L.M., Petrov M.L., Vasilyev A.V., Averin A.D., Beletskaya I.P., Nenajdenko V.G., Beloglazkina E.K., et. al.

An overview of the main scientific achievements of Russian universities in the field of organic chemistry over the period 2018–2023 is presented.

Gallyamova R., Dokichev V., Musin F.

The paper describes the modification conducted for the PAN carbon fiber surfaces in the solutions of nitric and sulphuric acids. The authors studied the impact of modification parameters such as temperature, acid concentration, time and ratio of the nitrosulphuric acid on the occurrence of reactive groups on the fiber surface. The authors revealed the presence of carboxylic and ketone reactive groups in the range of 1663-1798 and 1568 cm-1 in the IR spectra of carbon fibers. The use of the nitrosulphuric acid did not identify sulfur-containing functional groups on the carbon fiber IR spectra. Preliminary acid treatment of the carbon fiber surface led to the formation of uniform continuous coating of a SiO2 barrier being 127 ± 30 μm by a sol-gel method.

Cohen R.D., Wood J.S., Lam Y., Buevich A.V., Sherer E.C., Reibarkh M., Williamson R.T., Martin G.E.

Density functional theory (DFT) benchmark studies of 1H and 13C NMR chemical shifts often yield differing conclusions, likely due to non-optimal test molecules and non-standardized data acquisition. To address this issue, we carefully selected and measured 1H and 13C NMR chemical shifts for 50 structurally diverse small organic molecules containing atoms from only the first two rows of the periodic table. Our NMR dataset, DELTA50, was used to calculate linear scaling factors and to evaluate the accuracy of 73 density functionals, 40 basis sets, 3 solvent models, and 3 gauge-referencing schemes. The best performing DFT methodologies for 1H and 13C NMR chemical shift predictions were WP04/6-311++G(2d,p) and ωB97X-D/def2-SVP, respectively, when combined with the polarizable continuum solvent model (PCM) and gauge-independent atomic orbital (GIAO) method. Geometries should be optimized at the B3LYP-D3/6-311G(d,p) level including the PCM solvent model for the best accuracy. Predictions of 20 organic compounds and natural products from a separate probe set had root-mean-square deviations (RMSD) of 0.07 to 0.19 for 1H and 0.5 to 2.9 for 13C. Maximum deviations were less than 0.5 and 6.5 ppm for 1H and 13C, respectively.

Andriyashina N.M., Grabovskii S.A., Safiullin R.L.

Background: 1,1-Bishydroperoxides are used as oxidizing agents, radical initiators, in addition, studies of biological activity show the promise of this area of research. Objective: There are currently no kinetic data on the thermal stability of these peroxides in various solvents. Therefore, we investigated the thermal stability of 1,1-dihydroperoxycyclohexane as the most widely used at present. Methods: The rate constants and activation parameters were measured at the temperature range of 100-170 C in the presence of 2-naphthol, which inhibits the induced decomposition of the peroxide by free radicals. Peroxide concentration was determined by iodometric method. Results: The rate constants of the reaction with the solvents and of the monomolecular decomposition of the peroxide were determined. Conclusion: The use of DHPC as a radical initiator requires taking into account its reactions with the solvent and/or monomer, in addition to its monomolecular decomposition with the formation of free radicals.

Alam M.J., Alam O., Naim M.J., Nawaz F., Manaithiya A., Imran M., Thabet H.K., Alshehri S., Ghoneim M.M., Alam P., Shakeel F.

Pyrazole, an important pharmacophore and a privileged scaffold of immense significance, is a five-membered heterocyclic moiety with an extensive therapeutic profile, viz., anti-inflammatory, anti-microbial, anti-anxiety, anticancer, analgesic, antipyretic, etc. Due to the expansion of pyrazolecent red pharmacological molecules at a quicker pace, there is an urgent need to put emphasis on recent literature with hitherto available information to recognize the status of this scaffold for pharmaceutical research. The reported potential pyrazole-containing compounds are highlighted in the manuscript for the treatment of cancer and inflammation, and the results are mentioned in % inhibition of inflammation, % growth inhibition, IC50, etc. Pyrazole is an important heterocyclic moiety with a strong pharmacological profile, which may act as an important pharmacophore for the drug discovery process. In the struggle to cultivate suitable anti-inflammatory and anticancer agents, chemists have now focused on pyrazole biomolecules. This review conceals the recent expansion of pyrazole biomolecules as anti-inflammatory and anticancer agents with an aim to provide better correlation among different research going around the world.

Golovanov A.A., Itakhunov R., Odin I.S., Gusev D., Grabovskiy S.A., Gordon K.V., Vologzhanina A.V., Sokov S., Sosnin I.M.

Condensation of 1,5-disubstituted pent-1-en-4-yn-1-ones with arylhydrazines in acidified alcohol results mainly in the formation of the corresponding arylhydrazones with traces of the side products of cyclization at the double bond - 1,5-diaryl-3-(arylethynyl)-4,5-dihydro-1H-pyrazoles (pyrazolines). Arylhydrazones are cyclized only by refluxing in high-boiling polar solvents (DMF and ethylene glycol), with the selective formation of 1,5-disubstituted 3-styrylpyrazoles in up to 77-95% yields. Thermodynamically, the cyclization of arylhydrazones at the triple bond is the most preferable pathway, as shown by DFT calculations and preparative synthesis experiments. Thus, we demonstrate that the reactions of arylhydrazines with 1,5-disubstituted pent-1-en-4-yn-1-ones lead to the formation of arylhydrazones and side pyrazoline impurities in a parallel (not consecutive) manner. 2-Hydrazinylpyridine interacts with 1,5-disubstituted pent-1-en-4-yn-1-ones in some other way, giving not pyridinylhydrazones but 2-(5-styryl-3-phenyl-1H-pyrazol-1-yl)pyridines (despite the acidity of the medium). The authors have developed a gram-scale synthesis method for these compounds, which were obtained in up to 60-82% yields. Besides, we have developed the synthesis method for certain styrylpyrazoles, which are quite promising substances for use as fluorescent probes. Their spectral-luminescence characteristics were examined as well as their complexing with Hg2+, Cd2+, and Pb2+ ions.

Kuciński K., Hreczycho G.

The catalytic synthesis of silylamines mediated by s- and p-block catalysts is largely underdeveloped. Herein, commercially available potassium bis(trimethylsilyl)amide serves as an efficient alternative to transition metal complexes. N-H/Si-C dealkynative coupling was achieved by means of user-friendly main-group catalysis with ample substrate scope and high chemoselectivity.

Li G., Cheng Y., Han C., Song C., Huang N., Du Y.

Pyrazole is a five-membered heterocycle bearing two adjacent nitrogen atoms. Both pharmaceutical agents and natural products with pyrazole as a nucleus have exhibited a broad spectrum of biological activities. In the last few decades, more than 40 pyrazole-containing drugs have been approved by the FDA for the treatment of a broad range of clinical conditions including celecoxib (anti-inflammatory), CDPPB (antipsychotic), difenamizole (analgesic), etc. Owing to the unique physicochemical properties of the pyrazole core, pyrazole-containing drugs may exert better pharmacokinetics and pharmacological effects compared with drugs containing similar heterocyclic rings. The purpose of this paper is to provide an overview of all the existing drugs bearing a pyrazole nucleus that have been approved or in clinical trials, involving their pharmacological activities and SAR studies.

Mallesh R., Khan J., Pradhan K., Roy R., Jana N.R., Jaisankar P., Ghosh S.

The formation and accumulation of amyloid beta (Aβ) peptide are considered the crucial events that are responsible for the progression of Alzheimer's disease (AD). Herein, we have designed and synthesized a series of fluorescent probes by using electron acceptor-donor end groups interacting with a π-conjugating system for the detection of Aβ aggregates. The chemical structure of these probes denoted as RMs, having a conjugated π-system (C═C), showed a maximum emission in PBS (>600 nm), which is the best range for a fluorescent imaging probe. Among all these probes, RM-28 showed an excellent fluorescence property with an emission maximum of >598 nm upon binding to Aβ aggregates. RM-28 also showed high sensitivity (7.5-fold) and high affinities toward Aβ aggregates (Kd = 175.69 ± 4.8 nM; Ka = 0.5 × 107 M-1). It can cross the blood-brain barrier of mice efficiently. The affinity of RM-28 toward Aβ aggregates was observed in 3xTg-AD brain sections of the hippocampus and cortex region using a fluorescent imaging technique, as well as an in vitro fluorescence-based binding assay with Aβ aggregates. Moreover, RM-28 is highly specific to Aβ aggregates and does not bind with intracellular proteins like bovine serum albumin (BSA) and α-synuclein (α-Syn) aggregates. The results indicate that the probe RM-28 emerges as an efficient and veritable highly specific fluorescent probe for the detection of Aβ aggregates in both in vitro and in vivo model systems.

Baeva L.A., Biktasheva L.F., Fatykhov A.A., Galimzyanova N.F.

Radulov P.S., Mozzhegorov A.V., Mulina O.M., Yaremenko I.A., Ilovaisky A.I., Terent’ev A.O.

A method was developed for the synthesis of β-triazolyl sulfones from vinylsulfones and 1,2,4-triazoles in the presence of sodium triazolide taken as the base. The reaction was carried out in DMSO at room temperature for 120 h. The target compounds were obtained in 25–89% yields.

Odin I.S., Chertov A.Y., Grigor’eva O.B., Golovanov A.A.

An interaction of 1,5-diaryl-3-X-pent-4-yn-1-ones (where X stands for piperidin-1-yl, morpholin-4-yl, 4-methylpiperazin-1-yl) with arylhydrazines proceeds at room temperature and results in 3-aryl-5-arylethynyl-1-phenyl-4,5-dihydro-1H-pyrazoles with up to 57-73% yields. Under similar conditions, the cyclocondensation of conjugated 2,4,1-enynones with arylhydrazine proceeds only in the presence of cyclic amines. 1,5-Diaryl-3-X-pent-4-yn-1-ones are reported as synthetic equivalents of conjugated 2,4,1-enynones in reactions with arylhydrazines. On the basis of obtained data, there are highly efficient methods developed for the synthesis of 5-arylethynyl-substituted 4,5-dihydro-1H-pyrazoles, as well as for similarly structured 1H-pyrazoles prepared by oxidation in AcOH. Presented products possess quite marked fluorescent abilities. Emission maximum wavelengths are located at 453-465 and 363-400 nm, respectively; certain compounds show extremely large Stokes shifts that may reach 91,000 cm-1.

Han J.M., Kim Y.J., Jung H.J.

Glioblastoma stem-like cells (GSCs) drive tumor initiation, cancer invasion, immune evasion, and therapeutic resistance and are thus a key therapeutic target for improving treatment for glioblastoma multiforme (GBM). We previously identified calcium/calmodulin-dependent protein kinase II (CaMKII) as an emerging molecular target for eliminating GSCs. In this study, we aim to explore a new CaMKII-targeted synthetic lethal therapy for GSCs. Through high-throughput drug combination screening using CaMKII inhibitors and a bioactive compound library in GSCs, neurokinin 1 receptor (NK1R) inhibitors such as SR 140333 and aprepitant are found to be potential anticancer agents that exhibit chemical synthetic lethal interactions with CaMKII inhibitors, including hydrazinobenzoylcurcumin (HBC), berbamine, and KN93. Combined treatment with NK1R and CaMKII inhibitors markedly suppresses the viability and neurosphere formation of U87MG- and U373MG-derived GSCs. In addition, the combination of HBC and NK1R inhibitors significantly inhibits U87MG GSC tumor growth in a chick embryo chorioallantoic membrane (CAM) model. Furthermore, the synthetic lethal interaction is validated using RNA interference of CaMKIIγ and NK1R. Notably, the synthetic lethal effects in GSCs are associated with the activation of caspase-mediated apoptosis by inducing p53 expression and reactive oxygen species generation, as well as the suppression of stemness marker expression by reducing nuclear factor-kappa B (NF-κB) activity. This follows the downregulation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling and a decrease in intracellular calcium concentration. Moreover, NK1R affects CaMKIIγ activation. These findings demonstrate that NK1R is a potential synthetic lethal partner of CaMKII that is involved in eradicating GSCs, and they suggest a new CaMKII-targeted combination therapy for treating GBM.

Rostami H., Shiri L., Khani Z.

One important class of heterocyclic compounds, are pyrazole derivatives. These compounds consist of a pyrazole core and have many biological and pharmacological activities. Also, some of natural products having pyrazole molecules in their structures that give particular properties to these compounds. Today, interesting to nanoparticles due to the special characteristics of them for the organic synthesis, is increased. In this review, we focused on the synthesis different derivatives of pyrazole using nanoparticles.

Das S., Indurthi H.K., Asati P., Saha P., Sharma D.K.

Benzothiazole-based fluorescent probes are formed by decorating benzothiazole fluorophore with a small chemical fragment capable of detecting a particular biological species or physiological condition. Due to a variety of their photophysical mechanism, like, intramolecular charge transfer (ICT), excited-state intramolecular proton transfer (ESIPT), photoinduced electron transfer (PET), and aggregation-induced emission (AIE), these fluorescent probes selectively interact with various analytes and lead to change in their luminescence features that afford the detection of the analyte. These probes showed advantages of large Stokes shift, high quantum yields, and excellent color transitions. Benzothiazole fluorescent probes can be applied to diagnose various diseases or disorders by monitoring essential biomolecules by imaging cells or intracellular organelles. To date, several benzothiazole-based small molecular probes have been reported. The current review is mainly centered on the recent advances made by these fluorescent probes in the last five years.

Huang Q., Liu T., Ma D., Liu J., Ren T., Wu W., Zhang J.

28 Novel pyrazoline compounds containing pyrazole units have been synthesized and characterized. The crystal structures of C 1 and B 6 showed that these pyrazoline derivatives could form 3D layered structures through face-to-face stacking of aromatic rings , and they were more inclined to form H-type aggregation in poor solvent. Compound C 4 was selected as the standard sample to study their properties of aggregation-induced emission enhancement (AIEE) and reversible mechanical chromoluminescence (MFC) behaviors in THF/cyclohexane. And the results suggested the formation of H-type aggregation, and the RIR and RIV phenomenon in the aggregated state led to strong fluorescence emission behavior in high fc solvent. The analysis of fluorescence emission spectroscopy indicated that the fluorescence emission of C 4 could be selectively quenched by chloroform . Meanwhile, compound C 4 can selectively recognize NO 3 − in CH 2 Cl 2 . The studies of fluorescence quenching mechanism showed that compound C 4 could be oxidized by oxygen in the air to form a new compound C 4-1 in CHCl 3 solvent or in the presence of NO 3 − , leading to the fluorescence quenching of C 4 . Density functional theory calculations also confirmed the results. • A series of novel pyrazoline derivatives with aggregation-induced luminescence enhancement (AIEE) were designed and synthesized. • The AIEE behavior and MFC behavior of compound C 4 were studied in detail. • Compound C 4 has good selectivity to NO 3 − , and could be applied to qualitative detection of NO 3 − on test paper Strips. • Compound C 4 had a certain solvent selectivity and showed obvious fluorescence quenching in chloroform.