Sadovnikov, Kirill S

Sadovnikov K.S., Nazarov I.V., Zhigarev V.A., Danshina A.A., Makarov I.S., Bermeshev M.V.

Metathesis homo- and copolymerization of bifunctional monomers bearing two norbornene moieties was studied. The monomers were synthesized from cis-5-norbornene-exo-2,3-dicarboxylic anhydride and various diamines (hexamethylenediamine, decamethylenediamine, 1R,3S-isophoronediamine). The metathesis homopolymerization of these bis(nadimides) in the presence of the second-generation Grubbs catalyst afforded glassy cross-linked polymers in more than 90% yields. The metathesis copolymerization of the bis(nadimides) and a monofunctional norbornene derivative containing the β-pinene fragment also resulted in insoluble cross-linked polymers in nearly quantitative yields. The structures and purity of the synthesized polymers were confirmed via IR spectroscopy and CP/MAS NMR spectroscopy. Conditions for the fabrication of mechanically strong solution-cast thin films based on copolymers synthesized from the comonomers mentioned above were determined by varying the content of the cross-linking agent. It was shown that the films made in this way are stable in a range of organic solvents and could be useful as semipermeable or membrane materials for use in liquid organic media. The permeability of the polymer films in question to 1-phenylethanol and mandelic acid was studied. The results obtained are discussed along with the data from the DSC, TGA, and powder X-ray diffraction studies of the properties of the synthesized metathesis homo- and copolymers.

Sadovnikov K., Vasilenko D., Astakhova N., Sazonov A., Yakushev A., Gracheva Y., Grishin Y., Tafeenko V., Milaeva E., Averina E.

ABSTRACTA large series of previously unknown isoxazole containing difluoroboron β‐diketonate has been designed and synthesized from the available starting compounds. The photophysical properties of obtained compounds were studied, and the effects of the substituents in aromatic and isoxazole cycles of the BF2 complexes on the fluorescence were investigated. The effect of solvatochromism were demonstrated. Cytotoxic activity against MCF‐7 (breast carcinoma), HCT‐116 (colon carcinoma), A549 (pulmonary carcinoma) and WI38 (fibroblasts from lung tissue) cell lines was tested and moderate toxicity in the concentration range of 10–100 μM was found for several compounds.

Khrychikova A.P., Bermesheva E.V., Sadovnikov K.S., Bekeshev V.G., Bermeshev M.V.

Stepanyants V.R., Nazemutdinova V.R., Zhigarev V.A., Sadovnikov K.S., Wozniak A.I., Morontsev A.A., Bermeshev M.V.

The interaction of the second-generation Grubbs catalyst and dimethyl maleate is investigated. It is shown that this interaction affords a new ruthenium-carbene complex capable of participating in the metathesis reaction. The metathesis homopolymerization of cyclooctene and 5-n-butyl-2-norbornene mediated by the first- or second-generation Grubbs catalyst in the presence of dimethyl maleate acting as a chain transfer agent is studied in detail. Conditions for the synthesis of previously unknown telechelic poly(5-n-butyl-2-norbornene) are optimized. The formation of heterodyads between the polyene block and dimethyl maleate fragments is revealed. Effect of the concentration of initial reactants, their ratio, accessibility of the main-chain double bond of polyene, catalyst type, temperature, and reaction time on the molecular weight and depth of the cross-metathesis reaction is explored. The efficiency of using dimethyl maleate as a chain transfer agent is demonstrated.

Sadovnikov K.S., Vasilenko D.A., Gracheva Y.A., Grishin Y.K., Roznyatovsky V.A., Tafeenko V.A., Astakhova N.E., Burtsev I.D., Milaeva E.R., Averina E.B.

AbstractA simple two‐step protocol for the synthesis of 3‐aryl/hetaryl‐4‐nitro‐5‐styrylisoxazole was elaborated. A large series of novel 5‐styrylisoxazoles (36 compounds) containing various substituents at positions 3 and 5 of isoxazole cycle was obtained. The title compounds revealed fluorescent properties in visible region, possessing emission maximum up to 610nm. The effect of solvatochromism and chemosensor properties towards a number of metal cations were demonstrated. Cytotoxic activity against MCF‐7 (breast carcinoma), HCT‐116 (colon carcinoma), A549 (pulmonary carcinoma) and WI38 (fibroblasts from lung tissue) cell lines was tested and toxicity in the concentration range of 10–100 μM was found for several compounds.

Zefirov N.A., Nurieva E.V., Mamaeva A.V., Vasilenko D.A., Sadovnikov K.S., Averina E.B., Kolchanova A.Y., Milaeva E.R., Zefirova O.N.

A series of podophyllotoxin and epipodophyllotoxin esters with methylisoxazole fragments containing a halogen atom or a nitro group at position 4 of the heterocycle was synthesized. The starting isoxazolecarboxylic acids were obtained by bromination, iodination, or nitration of 5-methylisoxazole-3-carboxylic acid, which then were converted to the target esters by esterification in the DCC/DMAP or EDC/DMAP system. The results of molecular docking of podophyllotoxin and epipodophyllotoxin esters with the iodine-containing isoxazole derivatives predicted their ability to bind to tubulin and topoisomerase II, respectively, and do not exclude the possibility of the formation of halogen bonds with target proteins. The primary bioscreening showed that all compounds obtained at a concentration of 100 nmol L−1 caused a decrease in the number of A549 and VA13 cells by 40–60% after 72 h of treatment.

Spiridonov V.V., Sadovnikov K.S., Vasilenko D.A., Sedenkova K.N., Lukmanova A.R., Markova A.A., Shibaeva A.V., Bolshakova A.V., Karlov S.S., Averina E.B., Yaroslavov A.A.

Water-dispersible complexes of 4-methyl- N -[5-methyl-3-(3,4,5-trimethoxyphenyl)isoxazol-4-yl]benzamide possessing anticancer activity were prepared by its immobilization with biocompatible polymer nanocontainers based on sodium alginate cross-linked with Ca 2+ and Mg 2+ ions. It was found that this isoxazole derivative retains its structure during immobilization. Colloidal stable nanocontainers filled with this compound exhibit toxicity toward the colon carcinoma (HCT116) tumor cell line.

Sadovnikov K.S., Vasilenko D.A., Gracheva Y.A., Zefirov N.A., Radchenko E.V., Palyulin V.A., Grishin Y.K., Vasilichin V.A., Shtil A.A., Shevtsov P.N., Shevtsova E.F., Kuznetsova T.S., Kuznetsov S.A., Bunev A.S., Zefirova O.N., et. al.

AbstractA series of novel antimitotic agents was designed using the replacement of heterocyclic cores in two tubulin‐targeting lead molecules with the acylated 4‐aminoisoxazole moiety. Target compounds were synthesized via heterocyclization of β‐aryl‐substituted vinylketones by tert‐butyl nitrite in the presence of water as a key step. 4‐Methyl‐N‐[5‐methyl‐3‐(3,4,5‐trimethoxyphenyl)isoxazol‐4‐yl]benzamide (1aa) was found to stimulate partial depolymerization of microtubules of human lung carcinoma A549 cells at a high concentration of 100 µM and to totally inhibit cell growth (IC50 = 0.99 µM) and cell viability (IC50 = 0.271 µM) in the nanomolar to submicromolar concentration range. These data provide evidence of the multitarget profile of the cytotoxic action of compound 1aa. The SAR study demonstrated that the 3,4,5‐trimethoxyphenyl residue is the key structural parameter determining the efficiency both towards tubulin and other molecular targets. The cytotoxicity of 3‐methyl‐N‐[5‐methyl‐3‐(3,4,5‐trimethoxyphenyl)isoxazol‐4‐yl]benzamide (1ab) to the androgen‐sensitive human prostate adenocarcinoma cancer cell line LNCaP (IC50 = 0.301 µM) was approximately one order of magnitude higher than that to the conditionally normal cells lines WI‐26 VA4 (IC50 = 2.26 µM) and human umbilical vein endothelial cells (IC50 = 5.58 µM) and significantly higher than that to primary fibroblasts (IC50 > 75 µM).

Vasilenko D.A., Sadovnikov K.S., Sedenkova K.N., Karlov D.S., Radchenko E.V., Grishin Y.K., Rybakov V.B., Kuznetsova T.S., Zamoyski V.L., Grigoriev V.V., Palyulin V.A., Averina E.B.

A convenient synthetic approach to novel functionalized bis(isoxazoles), the promising bivalent ligands of the AMPA receptor, was elaborated. It was based on the heterocyclization reactions of readily available electrophilic alkenes with the tetranitromethane-triethylamine complex. The structural diversity of the synthesized compounds was demonstrated. In the electrophysiological experiments using the patch clamp technique on Purkinje neurons, the compound 1,4-phenylenedi(methylene)bis(5-aminoisoxazole-3-carboxylate) was shown to be highly potent positive modulator of the AMPA receptor, potentiating kainate-induced currents up to 70% at 10−11 M.

Vasilenko D.A., Dronov S.E., Parfiryeu D.U., Sadovnikov K.S., Sedenkova K.N., Grishin Y.K., Rybakov V.B., Kuznetsova T.S., Averina E.B.

An efficient protocol for the straightforward functionalization of the isoxazole ring via the reactions of aromatic nucleophilic substitution of the nitro group with various nucleophiles has been elaborated.

Sedenkova K.N., Vasilenko D.A., Zverev D.V., Sadovnikov K.S., Gracheva Y.A., Grishin Y.K., Kuznetsova T.S., Milaeva E.R., Averina E.B.

New 8-arylidene-4-cyanotetrahydroquinazoline N-oxides were obtained via the condensation of readily available 4-cyanotetrahydroquinazoline N-oxides with aromatic aldehydes. Some of the synthesized compounds revealed fluorescent properties and moderate cytotoxic activity.

Sadovnikov K.S., Vasilenko D.A., Sedenkova K.N., Rybakov V.B., Grishin Y.K., Alferova V.A., Kuznetsova T.S., Averina E.B.

5-Aminoisoxazoles bearing 3-positioned electron-withdrawing group react chemoselectively with trifluoroacetyl nitrate (generated from ammonium nitrate and trifluoroacetic anhydride) to give the corresponding 4-nitro derivatives in yields up to 80%. The results were rationalized by computation studies. Several 5-amino-4-nitroisoxazole-3-carboxilic acid derivatives revealed moderate antibacterial activity.

Sedenkova K.N., Terekhin A.V., Abdrashitova I.V., Vasilenko D.A., Sadovnikov K.S., Gracheva Y.A., Grishin Y.K., Holt T., Kutateladze A.G., Kuznetsova T.S., Milaeva E.R., Averina E.B.

An unusual condensation reaction of 2-methyltetrahydroquinazoline N-oxides with aromatic aldehydes was found. The reaction of 4-cyano substituted heterocycles as well as the use of microwave irradiation for 4-morpholinyl substituted heterocycles resulted in the condensation engaging the methylene group of the tetrahydroquinazoline fragment with simultaneous deoxygenation of the N-oxide. A preparative approach towards previously unknown pyrimidine-containing conjugated molecules was developed based on this process.

Averina E.B., Vasilenko D.A., Sadovnikov K.S., Sedenkova K.N., Kurova A.V., Grishin Y.K., Kuznetsova T.S., Rybakov V.B., Volkova Y.A.

A straightforward approach for the synthesis of 4-nitroisoxazoles has been developed via heterocyclization of aryl/hetaryl-substituted α,β-unsaturated ketones upon treatment with tetranitromethane-triethylamine (TNM-TEA) complex or t-BuONO. This strategy features high efficiency and wide substrate tolerance under simple reaction conditions.

Alexandrovskaya Y., Sadovnikov K., Sharov A., Sherstneva A., Evtushenko E., Omelchenko A., Obrezkova M., Tuchin V., Lunin V., Sobol E.

Penetration depth of near‐infrared laser radiation to costal cartilage is controlled by the tissue absorption and scattering, and it is the critical parameter to provide the relaxation of mechanical stress throughout the whole thickness of cartilage implant. To enhance the penetration for the laser radiation on 1.56 μm, the optical clearing solutions of glycerol and fructose of various concentrations are tested. The effective and reversible tissue clearance was achieved. However, the increasing absorption of radiation should be concerned: 5°C‐8°C increase of tissue temperature was detected. Laser parameters used for stress relaxation in cartilage should be optimized when applying optical clearing agents. To concentrate the absorption in the superficial tissue layers, magnetite nanoparticle (NP) dispersions with the mean size 95 ± 5 nm and concentration 3.9 ± 1.1 × 1011 particles/mL are applied. The significant increase in the tissue heating rate was observed along with the decrease in its transparency. Using NPs the respective laser power can be decreased, allowing us to obtain the working temperature locally with reduced thermal effect on the surrounding tissue.

Qneibi M., Hawash M., Bdir S., Bdair M., Idais T., Sarhan I., Touqan J.

Isoxazole carboxamide derivatives are intriguing modulators of ionotropic glutamate receptors; more specifically, their prospective analgesic activities based on non-opioid pathways have sparked widespread research. α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, especially Ca2+-permeable subtypes that are highly expressed in the spinal dorsal horn, play a critical role in nociceptive transmission and inflammatory pain. Herein, the neuromodulatory effects of these derivatives on AMPA receptor activity have been studied, focusing on their potential as modulators of AMPA receptors, a target implicated in pain and neurological disorders. The whole-cell patch clamp technique for electrophysiological recordings was used to investigate the effect of twelve isoxazole-4-carboxamide derivatives (CIC-1-12) on AMPA receptors’ whole-cell currents and kinetics, including deactivation and desensitization. The isoxazole-4-carboxamide derivatives tested as inhibitors of AMPA receptor activity were very potent, with an 8-fold inhibition by CIC-1 and a 7.8-fold reduction by CIC-2. Additionally, these compounds profoundly altered the biophysical gating properties of both homomeric and heteromeric receptor subunits. These findings emphasize the therapeutic promise of isoxazole-4-carboxamide derivatives due to their potential as AMPA receptor modulators. Their ability to affect receptor activity and gating properties makes them promising candidates for future treatments for controlling pain.

Eremeev R.O., Efremov A.M., Zakharova D.V., Beznos O.V., Sokolova E.V., Kalitin K.Y., Mukha O.Y., Vinogradova D.V., Veselov I.M., Shevtsov P.N., Dubova L.G., Babkov D.A., Spasov A.A., Shevtsova E.F., Lozinskaya N.A.

AbstractOxindole‐based natural indoles analogues retain the rigidity and size of the original indole ring system whilst introducing more 3‐dimensionality and potential increased water solubility. We report the first preparation of a diverse series of new melatonin analogues 4, 6, 11, 12 based on 3‐hydroxy‐2‐oxindoles (11) and hydroxy‐free 2‐oxindoles (4, 6, 12) and evaluated their ability to reduce intraocular pressure as well as their neuroprotective and antioxidant properties. Reductive amination was used to obtain new 5‐(benzylamino)‐substituted (indolin‐3‐yl)acetonitriles 11 and (indolin‐3‐yl)acetic acids 12 with high yields. Compounds 4 a, c, 6 a and 11 a, d, h, j–l demonstrated IOP reduction effect in range 15–27 % similar to the effect of reference compounds melatonin and timolol (12 % and 18 % reduction, respectively). 5‐(Benzylamino)‐substituted 3‐hydroxy‐2‐oxindoles 11, unlike compounds 4, 6, inhibited lipid peroxidation in range 2.075–13.012 μM. Inhibition of NQO2 associated with antioxidant properties of melatonin was also evaluated for synthesized compounds and it was found that compound 11 h showed the best NQO2 inhibitory activity with an IC50=39 μM (vs. melatonin IC50=64 μM). All synthesized compounds 4, 6, 11, 12 at a concentration of 30 μM do not possess the mitochondrial toxicity. Moreover, no disruption of tubulin polymerization was observed even in the presence of 100 μM of the compounds. Thus, 3‐hydroxy‐2‐oxindole derivatives 11 can be used for drug design of first‐in‐class antiglaucoma drugs with antioxidant and neuroprotective properties.

Musalov M.V.

The Special Issue “New Chemo-, Regio- and Stereoselective Reactions and Methods in Organic Synthesis” collects eight articles that have developed advanced approaches to the chemo-, regio- and stereoselective synthesis of novel important compounds, scaffolds, synthons, and practically valuable products [...]

Markov O.N., Beloglazkina E.K., Finko A.V.

The present review is devoted to oxaloacetic esters widely used in the synthesis of heterocyclic compounds and malonic ester derivatives. Three carbonyl groups of oxaloacetic esters have different reactivity allowing the tuning of overall reactivity of these compounds. The synthetic approaches to oxaloacetic esters, in particular the condensation of oxalates and acetates as well as the modern innovations in this classical synthesis that involved alkyl oxalyl chlorides, are reviewed. The main strategies for modification of oxaloacetic esters, e.g., halogenation and arylation, as well as the possibilities to overcome the side reactions are considered in detail. Special attention is paid to transformations of hydroxysuccinic esters and their oxidation to oxaloacetic esters. The reactions of acetylenedicarboxylic esters with carbonyl compounds, N- and S-oxides, and nitrones are also considered. The mechanisms of the rearrangement of the adducts of acetylenedicarboxylic ethers with heteroaromatic N-oxides are thoroughly discussed.

Burtsev I.D., Vasilenko D.A., Astakhova N.E., Averina E.B., Trofimov A.V., Kuzmin V.A.

Sadovnikov K., Vasilenko D., Astakhova N., Sazonov A., Yakushev A., Gracheva Y., Grishin Y., Tafeenko V., Milaeva E., Averina E.

ABSTRACTA large series of previously unknown isoxazole containing difluoroboron β‐diketonate has been designed and synthesized from the available starting compounds. The photophysical properties of obtained compounds were studied, and the effects of the substituents in aromatic and isoxazole cycles of the BF2 complexes on the fluorescence were investigated. The effect of solvatochromism were demonstrated. Cytotoxic activity against MCF‐7 (breast carcinoma), HCT‐116 (colon carcinoma), A549 (pulmonary carcinoma) and WI38 (fibroblasts from lung tissue) cell lines was tested and moderate toxicity in the concentration range of 10–100 μM was found for several compounds.

Khrychikova A.P., Bermesheva E.V., Sadovnikov K.S., Bekeshev V.G., Bermeshev M.V.

Ryzhikova O.V., Churkina A.S., Sedenkova K.N., Savchenkova D.V., Shakhov A.S., Lavrushkina S.V., Grishin Y.K., Zefirov N.A., Zefirova O.N., Gracheva Y.A., Milaeva E.R., Alieva I.B., Averina E.B.

AbstractSteroid dimers of natural and synthetic origin possess an unusual and complex molecular architecture that may lead to the realization of peculiar effects in biological systems, in particular in different cancer cell lines. In the present work, diastereoselective ring‐opening of mono‐ and polyoxiranes, containing a cyclooctane core, by azide‐anion was performed to yield a series of azidoalcohols with different types of symmetry. The products were involved in copper‐catalyzed azyde‐alkyne cycloaddition (CuAAC) reaction with ethinylestradiol and ethinyltestosterone, and the resulting steroids and steroid dimers with triazole linkers were screened for their antiproliferative activity via (3‐(4,5‐dimethylthiazol‐2‐yl)2,5‐diphenyl tetrazolium bromide) assay. All the compounds revealed cytotoxicity toward several cancer cell lines. The effect of the most potent compound, containing two estradiol moieties, on the microtubules (MT) dynamics was investigated by immunofluorescent microscopy. The disruption of the majority of interphase cell cytoplasmic MT and mitotic event disturbances in the presence of the studied compound were observed. The latter effect caused the appearance of numerous multinucleated cells.

Efremova M.M., Khashimova D.D., Kalinin N.S., Shtyrov A.A., Ryazantsev M.N., Spiridonova D.V., Govdi A.I., Balova I.A.

Zefirov N.A., Khvatov E.V., Nurieva E.V., Esaulkova Y.L., Volobueva A.S., Zarubaev V.V., Goryashchenko A.S., Yatsenko D.O., Uvarova V.I., Osolodkin D.I., Ishmukhametov A.A., Zefirova O.N.

Pyridine-containing amides of rimantadine (1-(1-adamantyl)ethylamine) were synthesized by the amidation of rimantadine hydrochloride by the corresponding acids in the NEt3—N,N′-dicyclohexylcarbodiimide (DCC)—4-(N,N-dimethylamino)pyridine (DMAP) system as the analogues of previously described antiviral compounds 1-adamantylmethyl-5-aminoisoxazole-3-carboxylate and N-{[5-(thien-2-yl)isoxazol-3-yl]methyl}adamantane-1-amine. The spectrum of antiviral activity against the rimantadine-resistant A/PR/8/34 strain of influenza A virus, tick-borne encephalitis virus (TBEV) strain Absettarov (European subtype), yellow fever virus (YFV) vaccine strain 17D, and West Nile virus (WNV) strain Strix nebulosa-12 was studied. The structure—activity relationships were discussed. Synthesized compounds efficiently inhibited the reproduction of TBEV and WNV. N-[1-(Adamantan-1-yl)ethyl]picolinamide efficiently inhibited the reproduction of enveloped viruses with both type I (influenza) and type II (flaviviruses) fusion proteins. The antiviral activity against the rimantadine-resistant influenza virus A/PR/8/34 and a low cytotoxicity (high selectivity index) were revealed for N-[1-(adamantan-1-yl)ethyl]-isonicotinamide.

Burtsev I.D., Vasilenko D.A., Astakhova N.E., Averina E.B., Trofimov A.V., Kuzmin V.A.

Alexandrovskaya Y.M., Kasianenko E.M., Sovetsky A.A., Matveyev A.L., Atyakshin D.A., Patsap O.I., Ignatiuk M.A., Volodkin A.V., Zaitsev V.Y.

AbstractOptical coherence elastography (OCE) demonstrated impressive abilities for diagnosing tissue types/states using differences in their biomechanics. Usually, OCE visualizes tissue deformation induced by some additional stimulus (e.g., contact compression or auxiliary elastic‐wave excitation). We propose a new variant of OCE with osmotically induced straining (OIS‐OCE) and demonstrate its application to assess various stages of proteoglycan content degradation in cartilage. The information‐bearing signatures in OIS‐OCE are the magnitude and rate of strains caused by the application of osmotically active solutions onto the sample surface. OCE examination of the induced strains does not require special tissue preparation, the osmotic stimulation is highly reproducible, and strains are observed in noncontact mode. Several minutes suffice to obtain a conclusion. These features are promising for intraoperative method usage when express assessment of tissue state is required during surgical operations. The “waterfall” images demonstrate the development of cumulative osmotic strains in control and degraded cartilage samples.

Proshin A.N., Trofimova T.P., Globa A.A., Dubrovskaya E.S., Zefirova O.N., Zefirov N.A., Tafeenko V.A., Dutova T.Y., Ugrak B.I., Serkov I.V.

1,1-Dibenzyl-3-(1-benzyl-1 1H-pyrazol-4-yl)-2-methylisothioureas containing structural elements both of known antioxidants and glutamate receptor modulators were proposed as compounds with a dual mode of biological action, namely the antioxidant activity and the ability to influence the glutamatergic signaling system. The target compounds were synthesized by the reaction of substituted 4-amino-1-benzylpyrazoles with thiophosgene followed by the condensation of the resulting 1-benzyl-4-isothiocyanato-1H-pyrazoles with dibenzylamine and the subsequent S-methylation of the resulting thioureas. 1,1-Dibenzyl-3-[1-(3,4-dichlorobenzyl)- and 1,1-dibenzyl-3-[1-(2,4-dichlorobenzyl)-1H-pyrazol-4-yl]-2-methylisothioureas were found to have a moderate ability to protect neuroblastoma cells against the toxic effect of hydrogen peroxide, making these compounds interesting for further study of the modulatory activity toward glutamate receptors.

Zhang Q., Zhang X., Zhang L., Pang S., He C.

Thabet H.K., Imran M., Imran M., Alaql S., Helal M.H.

N,N'-(methylenebis(1,4-phenylene))bis-(2-cyanoacetamide) was exploited as a precursor for synthesing some bis (benzylidene 5a-c, pyridines 7, 8, 10a,b, chromene 14, benzochromene 15) derivatives containing diphenyl-methylene spacer via the reaction with each of aromatic aldehydes, pentane-2,4-dione, acetaldehyde/ malononitrile, arylidene-malononitriles, ethyl cinnamates, 2-hydroxybenzaldehyde, and 2-hydroxy-1-naphthaldehyde). Bis(chromeno[3,4-c]pyridines 16&18) were synthesized via Michael's addition of malononitrile or ethyl cyanoacetate to bis(chromene) derivative. The newly prepared compound structures were established via ir, NMR spectroscopic data.

Sadovnikov K.S., Nazarov I.V., Zhigarev V.A., Danshina A.A., Makarov I.S., Bermeshev M.V.

Metathesis homo- and copolymerization of bifunctional monomers bearing two norbornene moieties was studied. The monomers were synthesized from cis-5-norbornene-exo-2,3-dicarboxylic anhydride and various diamines (hexamethylenediamine, decamethylenediamine, 1R,3S-isophoronediamine). The metathesis homopolymerization of these bis(nadimides) in the presence of the second-generation Grubbs catalyst afforded glassy cross-linked polymers in more than 90% yields. The metathesis copolymerization of the bis(nadimides) and a monofunctional norbornene derivative containing the β-pinene fragment also resulted in insoluble cross-linked polymers in nearly quantitative yields. The structures and purity of the synthesized polymers were confirmed via IR spectroscopy and CP/MAS NMR spectroscopy. Conditions for the fabrication of mechanically strong solution-cast thin films based on copolymers synthesized from the comonomers mentioned above were determined by varying the content of the cross-linking agent. It was shown that the films made in this way are stable in a range of organic solvents and could be useful as semipermeable or membrane materials for use in liquid organic media. The permeability of the polymer films in question to 1-phenylethanol and mandelic acid was studied. The results obtained are discussed along with the data from the DSC, TGA, and powder X-ray diffraction studies of the properties of the synthesized metathesis homo- and copolymers.

Feng T., Zhang L., Wu S., Shi X., Han Y.

This review summarizes the progress in recent decades regarding the structure–activity relationships of various well-defined metal-NHC catalysts in the polymerization of olefins, particularly α-olefins, styrene, norbornene, and others.

Alentiev A.Y., Syrtsova D.A., Nikiforov R.Y., Ryzhikh V.E., Belov N.A., Skupov K.M., Volkova Y.A., Ponomarev I.I.

Zhou T., Utecht-Jarzyńska G., Szostak M.

In the past two decades, NHCs (NHC = N-heterocyclic carbenes) have emerged as one of the most important classes of ligands in transition metal catalysis. Although historically 5-membered carbenes, such as imidazol-2-ylidenes, have been the dominant class of NHC ligands in transition metal catalysis, recently, ring expanded carbenes on 6-, 7-, 8-, 9- and 10-membered ring systems have been shown to provide significant advantages in numerous catalytic reactions embracing various metals, transformations and mechanisms. In this comprehensive review, we provide a survey of the applications of ring-expanded N-heterocyclic carbenes (reNHCs) in transition metal catalysis. Spanning from the initial reports on ring-expanded NHCs through June 2023, the review centers on the types of ring-expanded NHCs, their organometallic complexes and applications in catalytic processes. By delving into the impact of ring-expanded NHC ligands, the review aims to provide the reader with an understanding of the significance of this ligand class and its pivotal role in transition metal catalysis and organometallic chemistry.

Wozniak A.I., Bermesheva E.V., Petukhov D.I., Lunin A.O., Borisov I.L., Shantarovich V.P., Bekeshev V.G., Alentiev D.A., Bermeshev M.V.

AbstractThe development of polymers with high separation characteristics for the efficient removal of carbon dioxide from bio‐/natural gases is the key to reducing the environmental impact of CO2. In this work, preparation and gas‐separation properties of novel vinyl‐addition polynorbornenes containing oxirane‐moieties at spiro centers, which combine high CO2‐permeability with remarkable selectivities for separation of CO2 from its mixtures with nitrogen and methane are published. Gas permeability data of the epoxidized polymer based on 5‐ethylidene‐2‐norbornene exceed the Robeson upper bound of 2019 for the CO2/N2 system (CO2 permeability is 1000 Barrer, α(CO2/N2) = 67)). Separation experiments with mixtures of gases confirm the high separation performance of this polymer. In particular, the data for CO2/CH4 separation are above or close to the upper bound of 2018 for mixed gases. A similar effect of introducing oxirane moieties into spiro centers is also shown for another vinyl‐addition polymer derived from 5‐isopropylidene‐2‐norbornene and is not observed for a related polymer bearing oxirane moieties at the ends of side chains. A simple synthesis of the epoxidized polymer from available 5‐ethylidene‐2‐norbornene, combined with high CO2‐permeability and selectivities, may open a window for industrial applications of this polymer in important membrane processes, in particular, for natural/biogas upgrading.

Kabir M.H., Kannan S., Veetil K.A., Sun E.K., Kim T.

AbstractA series of poly(ethylene glycol)‐block‐poly(propylene glycol) (PEG/PPG)‐ and 5,6‐di(9H‐carbazol‐9‐yl)isoindoline‐1,3‐dione (2CZPImide)‐based crosslinked rubbery polymer membranes, denoted as PEG/PPG‐2CZPImide (x:y), are prepared from the norbornene‐functionalized PEG/PPG oligomer (NB‐PEG/PPG‐NB) and 2‐(bicyclo[2.2.1]hept‐5‐en‐2‐ylmethyl)‐5,6‐di(9H‐carbazol‐9‐yl)isoindoline‐1,3‐dione (2CZPImide‐NB) via ring‐opening metathesis polymerization (ROMP). The molar ratio (x:y) of the NB‐PEG/PPG‐NB (x) to 2CZPImide‐NB (y) monomers is varied from 10:1 to 6:1. X‐ray diffraction (XRD), scanning electron microscopy‐energy dispersive X‐ray spectroscopy (SEM‐EDS), and pure gas permeability studies reveal that the comonomer 2CZPImide‐NB successfully increases the d‐spacing among the crystalline PEG/PPG segments, hence enhancing the diffusivity of gases through the membranes. The synthesized membranes exhibit good CO2 separation performance, with CO2 permeabilities ranging from 311.1 to 418.1 Barrer and CO2/N2 and CO2/CH4 selectivities of 39.4–52.0 and 13.4–16.0, respectively, approaching the 2008 Robeson upper bound. Moreover, PEG/PPG‐2CZPImide (6:1), displaying optimal CO2 permeability and CO2/N2 and CO2/CH4 selectivities, shows long‐term stability against physical aging and plasticization resistance up to 20 days and 10 atm, respectively.

Feng H., Luo S.L., Swager T.M.

Ma W., Wright N., Wang Y.

Medentseva E.I., Khrychikova A.P., Bermesheva E.V., Borisov I.L., Petukhov D.I., Karpov G.O., Morontsev A.A., Nesterova O.V., Bermeshev M.V.

Cellulose acetate, some polyimides and polysulfones are mainly used in commercial membranes for gas separation processes. Although these polymers meet the desired combination of properties, the design of novel polymers possessing improved permeability and/or separation selectivity of gases could lead to enhanced gas separation efficiency and minimized energy costs. Here, we report gas permeability data of two isomeric vinyl-addition polymers derived from available ester-functionalized norbornenes that exhibit remarkable ideal and mixed gas selectivity as well as permeability for industrially important pairs of gases (CO2 with N2 and CH4). In particular, polynorbornene bearing acetoxy side groups (AcPNB) demonstrated carbon dioxide permeability of 270 Barrer and selectivity of CO2/N2 separation above 20, superposing to that of cellulose acetate (CA) in CO2 separation performance. The polymer containing methoxycarbonyl groups (McPNB), which is an isomer of AcPNB, showed even higher separation performance for CO2-containing gas mixtures. Carbon dioxide permeability and selectivity of CO2/N2 for McPNB exceeded 350 Barrer and 50, respectively. The data on CO2/N2 separation for McPNB are on the upper bound of Robeson plot of 2008 year. Mixed gas experiments performed for binary mixtures of CO2 with N2 and CH4 confirmed promising gas-separation parameters of the studied polymer, displaying attractive CO2/gas selectivity and CO2 permeability. Therefore, considering the simple and cheap syntheses of these polymers and the CO2 separation performance, they can be considered as promising candidates as selective layers for membrane gas separation processes.

Kilgallon L.J., McFadden T.P., Sigman M.S., Johnson J.A.

A tricyclononene and tricyclononadiene monomer library is studied experimentally and computationally to deepen understanding of structure propagation rate relationships in ROMP. A novel poly(tricyclononadiene) post-ROMP functionalization is explored.

Zotkin M.A., Alentiev D.A., Borisov R.S., Kozlova A.A., Borisov I.L., Shalygin M.G., Bermeshev M.V.

Gas transport properties of two sets of polynorbornenes bearing carbocyclic substituents of different nature (cyclohexyl, norbornyl, phenyl groups, and framed oligocyclic moieties) were systematically studied. The influence of side-chain carbocyclic substituents on gas permeability and separation selectivity for CO2-containing gas pairs and gaseous hydrocarbons was evaluated. It was found that the presence of carbocyclic moieties in side chains of polynorbornenes promotes the increase in gas permeability similarly to that of SiMe3 groups, with this effect being enhanced by the increase in the number of cycles in the substituents. As a result, P(CO2) of the metathesis polymer with pentacene-based substituents is equal to 1200 Barrer. Studied polynorbornenes with carbocyclic substituents displayed promising gas separation selectivities: CO2/N2 separation selectivity up to 41 (above the 2008 upper bound in the Robeson diagram) and solubility-controlled hydrocarbon separation selectivity up to 16 for the n-butane/methane gas pair. For the polymer with pentacene-based substituents, the separation of the mixture of hydrocarbons and aging were studied. The studies revealed that the mixed gas C4/C1 separation selectivity of this polymer reaches 4, and a two-time reduction of permeability occurs in 8.5 months. Therefore, the incorporation of carbocyclic groups in the side chains of polynorbornenes can be considered as an efficient strategy for the design of polymeric gas separation membrane materials.

Bermesheva E.V., Bermeshev M.

Vinyl‐addition polynorbornenes are versatile templates for the targeted design of high‐performance materials for various applications, such as membrane gas separation, micro‐ and optoelectronics, fuel cells, sensors, catalyst supports, etc. The cornerstone of the syntheses of these compounds is the choice of a catalyst for polymerization. Considering valuable developments in the field of catalysts for vinyl‐addition polymerization (VAP) summarized in previously published reviews, mention should be made that the research efforts were largely focused on two‐ and three‐component catalytic systems that suffer from the need to use a cocatalyst. The aim of this review is to highlight the advances in the design and development of single‐component catalysts for the VAP of norbornenes. Such catalysts are categorized into two main groups, viz., neutral and cationic catalysts. The catalyst structure, the catalytic activity, and the molecular weight characteristics of polymers produced on these catalysts are considered in detail. We believe this article can serve as a guide for developing future catalysts to gain access to new functional materials.

Lezhnin P.P., Nazarov I.V., Bermeshev M.V.

An optically active norbornene-type monomer was prepared from β-pinene (a monoterpene compound) and cis-5-norbornene-exo-2,3-dicarboxylic anhydride. The metathesis polymerization of this monomer in the presence of the first-generation Grubbs catalyst was studied, and a soluble high-molecular-mass metathesis polymer exhibiting film-forming properties was synthesized in 90% yield. The monomer and polymer structures were confirmed by 1Н and 13С NMR spectroscopy. The metathesis polymers obtained were characterized by thermal gravimetric analysis, differential scanning calorimetry, X-ray diffraction analysis, and polarimetry.

Singh H., Kumari V.S., Singh A.K., Kumar A., Kumar P.

Abstract: Tuberculosis (TB) is the major cause of mortality around the world and one of the most common diseases linked to AIDS. Due to the emergence of multi-drug resistance, extensive drug resistance, and total drug resistance strains, TB has become a difficult disease to treat. Isoxazole scaffold shows a wide range of biological activities, including anticancer, antibacterial, anti-tubercular, antiviral, and anti-inflammatory activities etc. Several isoxazole derivatives have been produced and few of them have shown comparable anti-tubercular activity with standard drugs. In this review, we have focused on reported isoxazole derivatives having antitubercular activity and summarized their structure-activity relationship.

Nazarov I.V., Khrychikova A.P., Medentseva E.I., Bermesheva E.V., Borisov I.L., Yushkin A.A., Volkov A.V., Wozniak A.I., Petukhov D.I., Topchiy M.A., Asachenko A.F., Ren X., Bermeshev M.V.

The polymers, combining saturated rigid main chains and imide moieties, were synthesized through vinyl-addition polymerization of substituted nadimides (VAP polymers) and assessed for the first time as potential membrane materials for gas separation. Previously difficult-to-access high molecular weight VAP polymers were readily prepared in good yields in the presence of (NHC)Pd-complexes (NHC – N-heterocyclic carbene ligand). As monomers, various racemic and chiral nadimides with the alkyl, aryl, fluoroaryl, and α-amino acid’ moieties were used. Thin polymeric membranes from VAP polymers exhibited desirable mechanical properties and good thermal stability. Related metathesis polymers from the nadimides were also obtained for the properties comparison. Pure (He, H2, O2, N2, CO2, CH4) and mixed gases (CO2/N2, CO2/CH4) permeation was investigated in detail for the prepared VAP polymers with different nature of imide-fragments. Valuable structure-property relationships were established, and it was found that VAP polynorbornene with fluoroaryl-groups in imides moieties exhibited the combination of high CO2 permeability with attractive CO2/N2 and CO2/CH4 selectivities. For the separation of the industrial relevant gas mixture, CO2/CH4, this polymer is above the 2008 upper bound for single gas separation and the 2018 upper bound for mixed-gas separation. With CO2 permeability of >1300 Barrer and CO2/CH4 separation selectivity of 29, the performance of the polymer exceeded that of other VAP and metathesis nadimide polymers.