Presnukhina, Sofia I

Presnukhina S.I., Kotlyarova V.D., Shetnev A.A., Baykov S.V., Turmanov R., Appazov N., Zhapparbergenov R., Zhussupova L., Togyzbayeva N., Cloete S.J., Korsakov M.K., Boyarskiy V.P., Petzer A., Petzer J.P.

Monoamine oxidase (MAO) plays a key role in the pathogenesis of central nervous system disorders, and MAO inhibitors have been used in the treatment of depression and Parkinson’s disease. In the search for new classes of MAO inhibitors, the present study investigated a series of 1,2,4-oxadiazin-5(6H)-one derivatives. This study provides the first optimization of the reaction conditions for the condensation of amidoximes with alkyl 2-halocarboxylates to yield the desired 1,2,4-oxadiazin-5(6H)-ones. The results of the in vitro MAO inhibition studies showed that the 1,2,4-oxadiazin-5(6H)-ones were indeed inhibitors of human MAO with the most potent inhibition observed for 5f (IC50 = 0.900 µM) and 7c (IC50 = 0.371 µM). It was concluded that, with appropriate substitution, 1,2,4-oxadiazin-5(6H)-one derivatives would act as good potency MAO-B inhibitors and lead compounds for the development of antiparkinsonian drugs. In Parkinson’s disease, MAO-B inhibitors enhance central dopamine levels and reduce MAO-mediated production of hydrogen peroxide and resultant oxidative injury. This study represents one of few works to investigate synthetic approaches and biological activities of the 1,2,4-oxadiazin-5(6H)-one class of heterocycles.

Baykov S.V., Semenov A.V., Presnukhina S.I., Tarasenko M.V., Shetnev A.A., Frontera A., Boyarskiy V.P., Kukushkin V.Y.

The cis- and trans-isomers of 6-(3-(3,4-dichlorophenyl)-1,2,4-oxadiazol-5-yl)cyclohex-3-ene-1-carboxylic acid (cis-A and trans-A) were obtained by the reaction of 3,4-dichloro-N′-hydroxybenzimidamide and cis-1,2,3,6-tetrahydrophthalic anhydride. Cocrystals of cis-A with appropriate solvents (cis-A‧½(1,2-DCE), cis-A‧½(1,2-DBE), and cis-A‧½C6H14) were grown from 1,2-dichloroethane (1,2-DCE), 1,2-dibromoethane (1,2-DBE), and a n-hexane/CHCl3 mixture and then characterized by X-ray crystallography. In their structures, cis-A is self-assembled to give a hybrid 2D supramolecular organic framework (SOF) formed by the cooperative action of O–H⋯O hydrogen bonding, Cl⋯O halogen bonding, and π⋯π stacking. The self-assembled cis-A divides the space between the 2D SOF layers into infinite hollow tunnels incorporating solvent molecules. The energy contribution of each noncovalent interaction to the occurrence of the 2D SOF was verified by several theoretical approaches, including MEP and combined QTAIM and NCIplot analyses. The consideration of the theoretical data proved that hydrogen bonding (approx. −15.2 kcal/mol) is the most important interaction, followed by π⋯π stacking (approx. −11.1 kcal/mol); meanwhile, the contribution of halogen bonding (approx. −3.6 kcal/mol) is the smallest among these interactions. The structure of the isomeric compound trans-A does not exhibit a 2D SOF architecture. It is assembled by the combined action of hydrogen bonding and π⋯π stacking, without the involvement of halogen bonds. A comparison of the cis-A structures with that of trans-A indicated that halogen bonding, although it has the lowest energy in cis-A-based cocrystals, plays a significant role in the crystal design of the hybrid 2D SOF. The majority of the reported porous halogen-bonded organic frameworks were assembled via iodine and bromine-based contacts, while chlorine-based systems—which, in our case, are structure-directing—were unknown before this study.

Konstantinova A.S., Shetnev A.A., Semenov A.V., Presnukhina S.I., Romanycheva A.A., Volobueva A.S., Zarubaev V.V., Baykov S.V., Korsakov M.K.

Method for the preparation of N-arylamino-1,2,4-oxadiazol-5(4H)-ones via reduction of N-nitrophenyl-1,2,4-oxadiazol-5(4H)-ones with tin(II) chloride has been developed. The results of experiments to study photophysical properties showed that the synthesized compounds have potential for use as fluorophores in the visible region of the spectrum. In addition, one of the obtained N-arylamino-1,2,4-oxadiazol-5(4H)-ones demonstrate antibacterial activity against both Gram-positive (S. Aureus) and Gram-negative (E. Coli) strains.

Presnukhina S.I., Tarasenko M.V., Geyl K.K., Baykova S.O., Baykov S.V., Shetnev A.A., Boyarskiy V.P.

We have developed a simple and convenient method for the synthesis of 3-aryl- and 3-hetaryl-1,2,4-oxadiazin-5-ones bearing an easily functionalizable (methoxycarbonyl)methyl group at position 6 via the reaction of aryl or hetaryl amidoximes with maleates or fumarates. The conditions for this reaction were optimized. Different products can be synthesized selectively in good yields depending on the base used and the ratio of reactants: substituted (1,2,4-oxadiazin-6-yl)acetic acids, corresponding methyl esters, or hybrid 3-(aryl)-6-((3-(aryl)-1,2,4-oxadiazol-5-yl)methyl)-4H-1,2,4-oxadiazin-5(6H)-ones. The reaction is tolerant to substituents’ electronic and steric effects in amidoximes. As a result, a series of 2-(5-oxo-3-(p-tolyl)-5,6-dihydro-4H-1,2,4-oxadiazin-6-yl)acetic acids, their methyl esters, and 1,2,4-oxadiazoles based on them were prepared and characterized by HRMS, 1H, and 13C NMR spectroscopy. The structures of three of them were elucidated with X-ray diffraction.

Baykov S.V., Semenov A.V., Presnukhina S.I., Novikov A.S., Shetnev A.A., Boyarskiy V.P.

• A series of 2,5-dibromothiophene-3-carboxylic acids derivatives was prepared. • X-ray structures of synthesized compounds determined and analyzed. • The competition between hydrogen and halogen bonding was revised. • Experimental data were supported via theoretical calculations. The competition between hydrogen (HB) and halogen (HaB) bonding in crystal structures of 2,5-dibromothiophene-3-carboxylic acid derivatives such as amides, esters, hydrazide and hydroxamic acid was studied by the analysis of both literature and newly obtained X-ray structures. It was found that the oxygen atom of carbonyl group either is involved in Br···O HaB or form NH···O HB with acidic protons of amide moieties and the latter interaction is more preferably. Theoretical calculations including topological analyses of the electron density distribution (QTAIM) and noncovalent interactions (NCI) approach were performed to prove the existence of these interactions and clarify their noncovalent nature.

Shetnev A.A., Vasilieva E.A., Proskurina I.K., Forostyanko A.S., Presnukhina S.I., Tarasenko M.V., Lebedev A.S., Ivanovskii S.A., Kotov A.D.

A preparative procedure has been developed for the synthesis of a series of new medicinally relevant 3-aryl-5-(aryloxymethyl)-1,2,4-oxadiazoles in 46–66% yields by alkylation of substituted phenols with 3-aryl-5-(chloromethyl)-1,2,4-oxadiazoles in the system K2CO3/KI/DMF. Poorly studied 3-R-4H-1,2,4-oxadiazin-5(6H)-ones were synthesized by a new method based on the reaction of methyl chloroacetate with amidoximes in the superbasic system t-BuONa/DMSO. The synthesized compounds at concentrations of up to 250 μg/mL showed no antibacterial activity against sensitive strains of Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas fluorescens, which supposedly suggests their low toxicity for human intestinal and mucous microflora.

Geyl K.K., Baykov S.V., Kalinin S.A., Bunev A.S., Troshina M.A., Sharonova T.V., Skripkin M.Y., Kasatkina S.O., Presnukhina S.I., Shetnev A.A., Krasavin M.Y., Boyarskiy V.P.

Relying on a recently suggested protocol that furnishes convenient access to variously substituted 2-pyridyl ureas, twelve hitherto unknown Cu(II) complexes have been synthesized in the present work and their structures were evaluated by elemental analysis, HRMS, IR spectroscopy, and X-ray diffraction study. Two structural motifs ([Cu(L)2Cl]+[Cl]− or (Cu(L)2Cl2) depending on the substitution pattern on the 2-pyridine fragment were revealed. In addition, antiproliferative action of the obtained compounds have been investigated against lung cancer cell lines (A549, NCI-H460, NCI-H1975), and healthy WI-26 VA4 cells were used to monitor non-specific cytotoxicity. Two nitro-group substituted complexes Cu(U3)2Cl2 (IC50 = 39.6 ± 4.5 μM) and Cu(U11)2Cl2 (IC50 = 33.4 ± 3.8 μM) demonstrate enhanced activity against the drug resistant NCI-H1975 cells with moderate selectivity toward normal WI-26 VA4 cells. The antiproliferative mechanism of cell death underlying the growth inhibitory effect of the synthesized complexes was studied via additional experiments, including the cell cycle analysis and the apoptosis induction test. Reassuringly, certain 2-pyridyl urea-based Cu(II) complexes exerted cell line-specific antiproliferative effect which renders them valuable starting points for further unveiling the anticancer potential of this class of coordination compounds.

Nadirova M.A., Khanova A.V., Zubkov F.I., Mertsalov D.F., Kolesnik I.A., Petkevich S.K., Potkin V.I., Shetnev A.A., Presnukhina S.I., Sinelshchikova A.A., Grigoriev M.S., Zaytsev V.P.

N -Furfuryl allylamines, readily accessible from corresponding furfurals or furfuryl amines, react with a broad range of arylsulfonyl chlorides with the formation of a 3a,6-epoxyisoindole core in one synthetic stage. Usually, in boiling water, the interaction sequence involves two consecutive steps: the Hinsberg reaction and the intramolecular Diels–Alder furanе (IMDAF) reaction. The scope and limitations of the proposed method were thoroughly investigated, and it was revealed that the key [4 + 2] cycloaddition step proceeds through an exo -transition state, giving rise to the exclusive formation of a single diastereomer of the target heterocycle. The method allows the ability to obtain N -sulfaryl-substituted 3a,6-epoxyisoindoles and 4a,7-epoxyisoquinolines, which are potentially useful substrates for further transformations and subsequent bioscreening, in particular antimicrobial activity. • A short IMDAF strategy to give 2-(arylsulfonyl)-3a,6-epoxyisoindoles from readily available initial materials was proposed. • Cascade of the Hinsberg / IMDAF Reactions is very simple and strongly depends on the characteristics of substituents. • Aforesaid epoxyisoindoles possess antibacterial activity against gram-negative or gram-positive sensitive bacteria strains.

Baykov S.V., Presnukhina S.I., Novikov A.S., Shetnev A.A., Boyarskiy V.P., Kukushkin V.Y.

A series of 2,5-dibromo-3-R-thiophenes (R = COONa 1, CN 2, CONH2 3, CON(H)Me 4, CON(H)Bn 5, CON(CH2CH2)2O 6, CON(H)NH2 7, CON(H)OH 8) were prepared and studied via high-resolution ESI-MS, 1H and 13...

Tarasenko M.V., Presnukhina S.I., Baikov S.V., Shetnev A.A.

A one-pot method for the synthesis of biphenylcarboxylic acids containing 1,2,4-oxadiazole ring in the NaOH–DMSO system was developed. The results of in vitro experiments showed that the synthesized compounds exhibit antibacterial activity against susceptible strains of E. coli and S. aureus.

Kletskov A.V., Frontera A., Sinelshchikova A.A., Grigoriev M.S., Zaytsev V.P., Grudova M.V., Bunev A.S., Presnukhina S., Shetnev A., Zubkov F.I.

Efficient approaches towards the synthesis of various N-substituted 1,3,5-triazinanes based on a transformation of N-alkyl-1,5,3-dioxazepanes or on a domino reaction involving condensation of various amines, amides, and paraformaldehyde are described for the first time. Mg(ClO4)2 was shown to be one of the most potent additives for the condensation. The proposed approaches permit the synthesis of a broad spectrum of substituted sym-triazinanes in good yields with relatively easy workup. In the case of the multicomponent reaction, the approach allows the preparation of the target substances from simple and easily accessible reagents. The representatives of the resulting compounds were found to possess no antimicrobial or cytotoxic activity in in vitro bioassays.

Presnukhina S., Tarasenko M., Baykov S., Smirnov S.N., Boyarskiy V.P., Shetnev A., Korsakov M.K.

A simple and convenient one-pot method is reported for the synthesis of (E)-3-(3-aryl(heteroaryl, alkyl)-1,2,4-oxadiazole-5-yl)acrylic acids utilizing readily accessible or commercially available substituted benzamidoximes and inexpensive exo-3,6-epoxy-1,2,3,6-tetrahydrophthalic anhydride. The method is based on the reaction of amidoximes with the anhydride in a basic medium at RT followed by an acid-catalyzed retro-Diels-Alder reaction. The observed stereoselective heterocyclization/retro-Diels-Alder cascade process is suitable for the synthesis of a wide range of substituted (E)-1,2,4-oxadiazole-5-ylacrylic acids featuring electron donating and electron withdrawing groups on the aryl moiety, as well as heteroaryl or alkyl substituents at position 3 of the 1,2,4-oxadiazole ring (42–79%; 15 examples).

Krasavin M., Shetnev A., Sharonova T., Baykov S., Kalinin S., Nocentini A., Sharoyko V., Poli G., Tuccinardi T., Presnukhina S., Tennikova T.B., Supuran C.T.

An expanded set of diversely substituted 1,2,4-oxadiazole-containing primary aromatic sulfonamides was synthesized and tested for inhibition of human carbonic anhydrase I, II, IX and XII isoforms. The initial biochemical profiling revealed a significantly more potent inhibition of cancer-related, membrane-bound isoform hCA IX (reaching into submicromolar range), on top of potent inhibition of hCA XII that is another cancer target. The observed structure-activity relationships have been rationalized by molecular modeling. Comparative single-concentration profiling of the carbonic anhydrase inhibitors synthesized for antiproliferative effects against normal (ARPE-19) and cancer (PANC-1) cell lines under chemically induced hypoxia conditions revealed several candidate compounds selectively targeting cancer cells. More in-depth characterization of these leads revealed two structurally related compounds that showed promising selective cytotoxicity against pancreatic cancer (PANC-1) and melanoma (SK-MEL-2) cell lines.

Senchurin V.S., Nayfert S.A., Osipov A.A., Zherebtsov D.A., Kantkhapazham R.

Tanwar A.S., Meyer F.

This highlight explores the key role of thiophene-based compounds in organic electronics, sensors, medicinal chemistry, solid-state reactions, crystal engineering, and supramolecular helices, using X-ray, DFT, and microscopy techniques.

Valtari A., Kalinin S., Jäntti J., Vanhanen P., Martina H., Arun T., Katja S., Tapani V., Vellonen K., Toropainen E., Ruponen M., Urtti A.

Cui F., García-López V., Wang Z., Luo Z., He D., Feng X., Dong R., Wang X.

Bunev A.S., Shetnev A.A., Shemchuk O.S., Kozhukhov P.K., Sharonova T.V., Tyuryaeva I.I., Khotin M.G., Ageev S.V., Kholmurodova D.K., Rizaev J.A., Semenov K.N., Sharoyko V.V.

Human carbonic anhydrase IX (CAIX) plays a key role in maintaining pH homeostasis of malignant neoplasms, thus creating a favorable microenvironment for the growth, invasion, and metastasis of tumor cells. Recent studies have established that inhibition of CAIX expressed on the surface of tumor cells significantly increases the efficacy of classical chemotherapeutic agents and makes it possible to suppress the resistance of tumor cells to chemotherapy, as well as to increase their sensitivity to drugs (in particular, to reduce the required dose of cytostatic agents). In this work, we studied the ability of new CAIX inhibitors based on substituted 1,2,4-oxadiazole-containing primary aromatic sulfonamides, to potentiate the cytostatic effect of gefitinib (selective inhibitor of epidermal growth factor receptor tyrosine kinase domain) under hypoxic conditions. We investigated a combined effect of gefitinib and CAIX inhibitors 4-(3-phenyl-1,2,4-oxadiazol-5-yl)thiophene-2-sulfonamide (1), 4-(5-(thiophene-3-yl)-1,2,4-oxadiazol-3-yl)benzenesulfonamide (2), 4-(3-(pyridin-2-yl)-1,2,4-oxadiazol-5-yl)thiophene-2-sulfonamide (3), and 4-(5-methyl-1,2,4-oxadiazol-3-yl)benzenesulfonamide (4) on gefitinib cytotoxicity, cell proliferation, activation of caspases-3/7, and cell cycle control in human lung adenocarcinoma A549 cells. It was found that the combinations of compounds 1 and 2 with gefitinib suppressed the invasive potential of A549 cells. Compound 1 had the greatest effect and can be considered as a promising candidate for further research.

Presnukhina S.I., Kotlyarova V.D., Shetnev A.A., Baykov S.V., Turmanov R., Appazov N., Zhapparbergenov R., Zhussupova L., Togyzbayeva N., Cloete S.J., Korsakov M.K., Boyarskiy V.P., Petzer A., Petzer J.P.

Monoamine oxidase (MAO) plays a key role in the pathogenesis of central nervous system disorders, and MAO inhibitors have been used in the treatment of depression and Parkinson’s disease. In the search for new classes of MAO inhibitors, the present study investigated a series of 1,2,4-oxadiazin-5(6H)-one derivatives. This study provides the first optimization of the reaction conditions for the condensation of amidoximes with alkyl 2-halocarboxylates to yield the desired 1,2,4-oxadiazin-5(6H)-ones. The results of the in vitro MAO inhibition studies showed that the 1,2,4-oxadiazin-5(6H)-ones were indeed inhibitors of human MAO with the most potent inhibition observed for 5f (IC50 = 0.900 µM) and 7c (IC50 = 0.371 µM). It was concluded that, with appropriate substitution, 1,2,4-oxadiazin-5(6H)-one derivatives would act as good potency MAO-B inhibitors and lead compounds for the development of antiparkinsonian drugs. In Parkinson’s disease, MAO-B inhibitors enhance central dopamine levels and reduce MAO-mediated production of hydrogen peroxide and resultant oxidative injury. This study represents one of few works to investigate synthetic approaches and biological activities of the 1,2,4-oxadiazin-5(6H)-one class of heterocycles.

Jiao L., Huang M., Ning D., Yang J., Xu J., Xu Q., Wu Q.

Programmable supramolecular materials assembled from chiral components are receiving increasing attention. Herein, we report a self-assembled racemic based on a halogenated Schiff base complex, [Cu3L2Cl2(H2O)] (L = N, N'-bis (3-Bromosalicylidene) ethylene-1,3-diaminopropane). Structural analysis reveals that the disappearance of molecular symmetry is closely related to the unique intramolecular 'rhombic-shape' halogen bonding of the compound. To the best of our knowledge, this is the first example of 'rhombic-shape' halogen bonding within a single molecule. To gain deeper mechanistic insight into the formation of this peculiar structure, we performed a series of structural analyses and theoretical calculations on the reported compound. The results suggest that the 'rhombic-shape' halogen bonding structure formed among the four Br atoms is asymmetric. This asymmetry structural feature further affects the molecular symmetry and serves as the primary factor inducing the special chirality in the molecule.

Mertsalov D.F., Lovtsevich L.V., Shchevnikov D.M., Dobrushina Y.M., Sorokina E.A., Grigoriev M.S., Zaytsev V.P.

The reaction of allyl(furfuryl)amines with aroyl isothiocyanates was studied. The reaction proceeded via an initial nucleophilic addition of the allylamine nitrogen atom to isothiocyanates and a subsequent spontaneous intramolecular Diels–Alder reaction involving the furan ring of intermediate N-allyl-N-furfurylthioureas with the formation of a single diastereomer of 3a,6-epoxyisoindoles.

Zaguzin A.S., Bondarenko M.A., Korobeynikov N.A., Usoltsev A.N., Fedin V.P., Adonin S.A.

Two new 3D metal-organic coordination polymers [Zn2(2-I-bdc)2bpen]n (1) and [Zn(I-ipa)bpen]n (2) based on zinc, 2-iodoterephthalate (2-I-bdc), 5-iodoisophthalate (5-I-ipa), and 1,2-bis(4-pyridyl)ethylene (bpen) have been prepared. The structure of these metal-organic coordination polymers has been established by X-ray diffraction.

Nair V.A., Radhakrishna V.Y., Khatik G.L.

AbstractAn efficient and eco-friendly procedure was developed for the synthesis of N-aryl-2-((3-aryl-1,2,4-oxadiazol-5-yl)thio)acetamides from N-aryl-2-thiocyanatoacetamides and substituted N-hydroxybenzimidoyl chlorides that were prepared easily from the commercially available anilines and aryl aldehydes, respectively. The N-aryl-2-thiocyanatoacetamide acts as a dipolarophile while the nitrile oxide formed in situ from substituted N-hydroxybenzimidoyl chloride acts as the nucleophilic partner in a 1,3-dipolar cycloaddition reaction mediated by triethylamine base in ethanol medium. The procedure affords excellent yields of desired products containing electron-withdrawing and electron-donating groups on the aromatic rings, in short reaction time with ease of operation. The procedure for the synthesis of scaffolds that are potentially valuable for their biological properties also offers the possibility of scale-up to higher quantities.

Katlenok E.A., Baykov S.V., Semenov A.V., Suslonov V.V., Kukushkin V.Y.

Mertsalov D.F., Shchevnikov D.M., Lovtsevich L.V., Novikov R.A., Khrustalev V.N., Grigoriev M.S., Romanycheva A.A., Shetnev A.A., Bychkova O.P., Trenin A.S., Zaytsev V.P.

A concise preparative IMDAF strategy for the synthesis of chalcogenurea-substituted 3a,6-epoxyisoindoles, which display antifungal and antibacterial activity, starting from readily available materials was proposed.

Kumar R., Kumar G., Mazumder D.A., Salahuddin S., Singh H., Kumar U., Abdullah M.M., Yar M.S., Kumar N.

Abstract: A five-membered heterocyclic compound known as 1,2,4-oxadiazole has one oxygen, two carbon, and two nitrogen atoms within a ring. Numerous studies have shown that 1,2,4-oxadiazole has the potential to be an essential moiety in many harmful pharmacological conditions. 1,2,4-oxadiazole and its derivatives have been used as an antiviral, cough suppressant, vasodilator, anxiolytic, etc. To synthesize a single molecule with potent pharmacological action, two or more pharmacophores are combined currently. This enhances pharmacological effects, facilitates interaction possible with many targets, and reduces the adverse effects related to them. It has been reported that synthesis of 1,2,4-oxadiazole and its analog is possible using a variety of methods. In this present review, we emphasized recently accepted synthetic methods for 1,2,4-oxadiazole and its analogs synthesis. Additionally, the structure-activity relationship concerning several pharmacological effects, interactions with various targets, and the utility of different techniques for the analysis and purification has been described. On the behalf of the above study, the researchers can use this review study to better understand their 1,2,4-oxadiazole research in the future.

Yıldırım A.

Tandem Diels–Alder reactions are often used for the straightforward formation of complex natural compounds and the fused polycyclic systems contained in their precursors. In the second step of this reaction, regio- and stereochemically controlled intramolecular cyclization leads to the formation of versatile nitrogen-containing tricyclic systems. However, these useful organic transformations are usually carried out in highly toxic organic solvents such as benzene, toluene, chloroform, etc. Despite recent efforts by 'green chemists', synthetic chemists still use these traditional toxic organic solvents in many of their reactions, even though safer alternatives are available. However, in addition to the harmful effects of these petrochemical solvents on the environment, the prediction that their resources will run out in the near future has led 'green chemists' to explore solvents that can be derived from renewable resources and used effectively in various organic transformations. In this context, we have shown for the first time that the 100% atom-economical tandem Diels–Alder reaction between aminofuranes and maleic anhydride can be carried out successfully in vegetable oils and waxes. The reaction was successfully carried out in sunflower seed oil, olive oil, oleic acid and lauryl myristate under mild reaction conditions. A series of epoxyisoindole-7-carboxylic acid and bisepoxyisoindole-7-carboxylic acids were obtained in good yields after a practical isolation procedure. The results obtained in this study demonstrate the potential of vegetable oils and their renewable materials to provide a reaction medium that is more sustainable than conventional organic solvents in cascade Diels–Alder reactions and can be used repeatedly without significant degradation. These materials also allow the reaction to be completed in less time, with less energy consumption and higher yields.

Sharma V., Vats L., Giovannuzzi S., Mohan B., Supuran C.T., Sharma P.K.

AbstractTwo novel series of hydrazinyl‐based benzenesulfonamides 9a–j and 10a–j were designed and synthesized using SLC‐0111 as the lead molecule. The newly synthesized compounds were evaluated for their inhibitory activity against four different human carbonic anhydrase (hCA) isoforms I, II, IX, and XII. Both the series reported here were practically inactive against the off‐target isozyme hCA I. Notably, derivative 10a exhibited superior potency (Ki of 10.2 nM) than acetazolamide (AAZ) against the cytosolic isoform hCA II. The hCA IX and XII isoforms implicated in tumor progression were effectively inhibited with Kis in the low nanomolar range of 20.5–176.6 nM and 6.0–127.5 nM, respectively. Compound 9g emerged as the most potent and selective hCA IX and XII inhibitor with Ki of 20.5 nM and SI of 200.1, and Ki of 6.0 nM and SI of 683.7, respectively, over hCA I. Furthermore, six compounds (9a, 9h, 10a, 10g, 10i, and 10j) exhibited significant inhibition toward hCA IX (Kis = 27.0, 41.1, 27.4, 25.9, 40.7, and 30.8 nM) relative to AAZ and SLC‐0111 (Kis = 25.0 and 45.0 nM, respectively). These findings underscore the potential of these derivatives as potent and selective inhibitors of hCA IX and XII over the off‐target hCA I and II.

Zainal Abidin A., Norrrahim M.N., Mohamed Shakrin N.N., Ibrahim B., Abdullah N., Abdul Rashid J.I., Mohd Kasim N.A., Ahmad Shah N.A.

Antimicrobial resistance (AMR) is a growing and concerning threat to global public health, necessitating innovative strategies to combat this crisis. Amidine-containing compounds have emerged as promising agents in the battle against AMR. This review gives a summary of recent advances from the past decade in studies of antimicrobial amidine-containing compounds with the aim to feature their structural diversity and the pharmacological relevance of the moiety to antimicrobial activity and their potential use in combating antimicrobial resistance, to the greatest extent possible. Highlighting is put on chemical structure of such compounds in relation to antimicrobial activities such as antibacterial, antifungal, and antiparasitic activities. Researchers commonly modify molecules containing amidine or incorporate amidine into existing antimicrobial agents to enhance their pharmacological attributes and combat antimicrobial resistance. This comprehensive review consolidates the current knowledge on amidine-containing compounds, elucidating their antimicrobial mechanisms and highlighting their promise in addressing the global AMR crisis. By offering a multidisciplinary perspective, we aim to inspire further research and innovation in this critical area of antimicrobial research.

Tang J., Yang R., Peng Y., Lin H., He X., Song Y., Wu K., Kang Y., Yang L.

AbstractOrganic frameworks‐based batteries with excellent physicochemical stability and long‐term high capacity will definitely reduce the cost, carbon emissions, and metal consumption and contamination. Here, an ultra‐stable and ultra‐thin perylene‐dicyandiamide‐based hydrogen organic framework (HOF) nanosheet (P‐DCD) of ≈3.5 nm in thickness is developed. When applied in the cathode, the P‐DCD exhibits exceptional long‐term capacity retention for alkali‐ion batteries (AIBs). Strikingly, for lithium‐ion batteries (LIBs), at current of 2 A g−1, the large reversible capacity of 108 mA h g−1 shows no attenuation within 5 000 cycles. For sodium‐ion batteries (SIBs), the related capacity retains 91.7% within 10 000 cycles compared to the initial state, significantly much more stable than conventional organic materials reported previously. Mechanism studies through ex situ and in situ experiments and theoretical density functional theory (DFT) calculations reveal that the impressive long‐term performance retention originates from the large electron delocalization, fast ion diffusion, and physicochemical stability within the ultra‐thin 2D P‐DCD, featuring π‐π and hydrogen bonding stacking, nitrogen‐rich units, and low impedance. The advantageous features demonstrate that rationally designed stable and effective organic frameworks pave the way to utilizing complete organic materials for developing next‐generation low‐cost and highly stable energy storage batteries.

Chu J., Liu Z., Yu J., Cheng L., Wang H., Cui F., Zhu G.

AbstractIn the emerging aqueous zinc ion batteries (AZIBs), proton (H+) with the smallest molar mass and fast (de)coordination kinetics is considered as the most ideal charge carrier compared with Zn2+ counterpart, however, searching for new hosting materials for H+ storage is still at its infancy. Herein, redox‐active hydrogen‐bonded organic frameworks (HOFs) assembled from diaminotriazine moiety decorated hexaazatrinnphthalene (HOF‐HATN) are for the first time developed as the stable cathode hosting material for boosting H+ storage in AZIBs. The unique integration of hydrogen‐bonding networks and strong π‐π stacking endow it rapid Grotthuss proton conduction, stable supramolecular structure and inclined H+ storage. As a consequence, HOF‐HATN displays a high capacity (320 mAh g−1 at 0.05 A g−1) and robust cyclability of (>10000 cycles at 5 A g−1) based on three‐step cation coordination storage. These findings get insight into the proton transport and storage behavior in HOFs and provide the molecular engineering strategy for constructing well‐defined cathode hosting materials for rechargeable aqueous batteries.

Konstantinova A.S., Shetnev A.A., Volobueva A.S., Korsakov M.K.

The possibilities of N-arylation of 1,2,4-oxadiazol-5(4H)-ones and 1,3,4-oxadiazol-2(3H)-ones with various electron-deficient chloro- and fluorine-substituted nitroarenes under the conditions of the classical activated nucleophilic substitution reaction were studied. A significant difference was found in the reactivity of 1,2,4- and 1,3,4-oxadiazolones in the N-arylation reactions. Methods for the synthesis of N-nitroaryl derivatives of 1,2,4- and 1,3,4-oxadiazolones, providing the target products of sufficient purity in yields of about 65–96%, were developed.

Yu D., Zhang H., Ren J., Qu X.

Hydrogen-bonded organic frameworks (HOFs) are an emerging attractive class of highly crystalline porous materials characterized by significant biocompatibility, rich chemical functionalities and well-defined porosity.

Wang Q., Li P., Wen H., Hu K., Huang Z., Chen J.

Hydrogen organic frameworks (HOFs) are a novel class of porous crystalline materials, which have attracted lots of attention in various applications. Nevertheless, HOFs-based electrochemical aptasensors have not been reported so far. In this work, we successfully constructed an electrochemical aptasensor based on HOFs constructed by 1,3,6,8-tetrakis[p-benzoic acid]pyrene. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to demonstrate the electrochemical performance of the as-synthesized HOF-based electrochemical aptasensorfor the sensitive and selective detection of oxytetracycline.

Begunov R.S., Chetvertakova A.V., Neganova M.E.

The efficiency of two strategies for the synthesis of N-(2-aminophenyl)-5-nitrobenzimidazole derivatives was studied. The promising route involves the stages of 1-(2,4-dinitro-phenyl)-1H-benzimidazole monoreduction at 2-positioned nitro group and tandem conversion involving recyclization of the intermediate N-(2-amino-4-nitrophenyl)-5-nitrobenz-imidazole.

Soleimani Abhari P., Gholizadeh S., Rouhani F., Li Y., Morsali A., Liu T.

Hydrogen-bonded frameworks (HOFs) are a new and appealing class of porous crystalline materials that are built from organic moieties through hydrogen bonding. Because of the brittle character of hydrogen bonding...

Cai Y., Gao J., Li J., Liu P., Zheng Y., Zhou W., Wu H., Li L., Lin R., Chen B.

AbstractDeveloping hydrogen‐bonded organic frameworks (HOFs) that combine functional sites, size control, and storage capability for targeting gas molecule capture is a novel and challenging venture. However, there is a lack of effective strategies to tune the hydrogen‐bonded network to achieve high‐performance HOFs. Here, a series of HOFs termed as HOF‐ZSTU‐M (M=1, 2, and 3) with different pore structures are obtained by introducing structure‐directing agents (SDAs) into the hydrogen‐bonding network of tetrakis (4‐carboxyphenyl) porphyrin (TCPP). These HOFs have distinct space configurations with pore channels ranging from discrete to continuous multi‐dimensional. Single‐crystal X‐ray diffraction (SCXRD) analysis reveals a rare diversity of hydrogen‐bonding models dominated by SDAs. HOF‐ZSTU‐2, which forms a strong layered hydrogen‐bonding network with ammonium (NH4+) through multiple carboxyl groups, has a suitable 1D “pearl‐chain” channel for the selective capture of propylene (C3H6). At 298 K and 1 bar, the C3H6 storage density of HOF‐ZSTU‐2 reaches 0.6 kg L−1, representing one of the best C3H6 storage materials, while offering a propylene/propane (C3H6/C3H8) selectivity of 12.2. Theoretical calculations and in situ SCXRD provide a detailed analysis of the binding strength of C3H6 at different locations in the pearl‐chain channel. Dynamic breakthrough tests confirm that HOF‐ZSTU‐2 can effectively separate C3H6 from multi‐mixtures.

Prinsloo I.F., Petzer J.P., Cloete T.T., Petzer A.

AbstractThe small molecule, isatin, is a well‐known reversible inhibitor of the monoamine oxidase (MAO) enzymes with IC50 values of 12.3 and 4.86 μM for MAO‐A and MAO‐B, respectively. While the interaction of isatin with MAO‐B has been characterized, only a few studies have explored structure–activity relationships (SARs) of MAO inhibition by isatin analogues. The current study therefore evaluated a series of 14 isatin analogues as in vitro inhibitors of human MAO‐A and MAO‐B. The results indicated good potency MAO inhibition for some isatin analogues with five compounds exhibiting IC50 < 1 μM. 4‐Chloroisatin (1b) and 5‐bromoisatin (1f) were the most potent inhibitors with IC50 values of 0.812 and 0.125 μM for MAO‐A and MAO‐B, respectively. These compounds were also found to be competitive inhibitors of MAO‐A and MAO‐B with Ki values of 0.311 and 0.033 μM, respectively. Among the SARs, it was interesting to note that C5‐substitution was particularly beneficial for MAO‐B inhibition. MAO inhibitors are established drugs for the treatment of neuropsychiatric and neurodegenerative disorders, while potential new roles in prostate cancer and cardiovascular disease are being investigated.

Maji S., Natarajan R.

AbstractThere is a strong and urgent need for efficient materials that can capture radioactive iodine atoms from nuclear waste. This work presents a novel strategy to develop porous materials for iodine capture by employing halogen bonding, mechanochemistry and crystal engineering. 3D halogen‐bonded organic frameworks (XOFs) with guest‐accessible permanent pores are exciting targets in crystal engineering for developing functional materials, and this work reports the first example of such a structure. The new‐found XOF, namely TIEPE‐DABCO, exhibits enhanced emission in the solid state and turn‐off emission sensing of acid vapors and explosives like picric acid in nanomolar quantity. TIEPE‐DABCO captures iodine from the gas phase (3.23 g g−1 at 75 °C and 1.40 g g−1 at rt), organic solvents (2.1 g g−1), and aqueous solutions (1.8 g g−1 in the pH range of 3–8); the latter with fast kinetics. The captured iodine can be retained for more than 7 days without any leaching, but readily released using methanol, when required. TIEPE‐DABCO can be recycled for iodine capture several times without any loss of storage capacity. The results presented in this work demonstrate the potential of mechanochemical cocrystal engineering with halogen bonding as an approach to develop porous materials for iodine capture and sensing.

Song G., Shi Y., Jiang S., Pang H.

AbstractIn recent years, metal‐organic frameworks, especially MOF‐based derivatives, have been regarded as one of the best candidate electrode materials for the next generation of advanced materials, due to high porosity, large surface area, modifiable functional groups as well as controllable chemical composition. This review presents the corresponding synthesis methods, structural design, and electrochemical performance of MOF‐derived materials, including metal oxides, metal sulfides, metal phosphides, and carbon materials, in high‐performance lithium‐ion batteries. Subsequently, the problems that exist in the current application of MOF‐based derivatives as electrodes in lithium‐ion batteries are discussed along with possible and feasible solutions. At last, some reasonable pathways and strategies for the design of MOF derivatives are also suggested.

Li N., Li B., Yu F., Zhang X., Fan X.

Eşme A., Kara Y.S.

Oxadiazines are heterocyclic compounds containing two nitrogen and one oxygen atom in a six-membered ring. The synthesis and crystal structure of 4-(4-methoxyphenyl)-6-methyl-3-phenyl-4H-1,2,4-oxadiazin-5(6H)-one (MPMP-OXA) was reported. The organic crystal structure of the synthesized compound was fully characterized by various spectroscopic techniques (Fourier Transform Infrared Spectroscopy, NMR and LC/MS-TOF) and single-crystal X-ray diffraction studies. The MPMP-OXA crystal structure crystallizes in the triclinic system and space group P-1 with a = 5.9395(15) Å, b = 11.471(3) Å, c = 11.901(3) Å, α = 70.075(4)°, β = 83.454(4)°, γ = 78.016(4)°, V = 744.9(3) Å3, Z = 2 cell parameters. This work is aimed to study the weak interactions in the crystal packing of a new synthesized oxadiazine derivate. The contributions of the most important intermolecular interactions in the crystal structure were investigated by 3D-Hirshfeld surface (HS) and 2D-fingerprint analysis. The CH···O interactions as the most important contributors to the crystal packing between the oxygen of the oxadiazine ring and the hydrogen atom of phenyl ring appear as bright red spots visible on the HS surface. The hydrogen-bonded interaction of MPMP-OXA has been investigated using noncovalent interactions approach. The molecular docking studies for the synthesized compound were performed to gain insight into the inhibition nature of this molecule against DNA Gyrase B Candida and 3-chymotrypsin-like protease (SARS-CoV main protease) proteins and resulted in good activities for new anti-agents. Lastly, Bioavailability, druggability as well as absorption, distribution, metabolism, excretion, and toxicity parameters (ADMET), and gastrointestinal absorption (BOILED-Egg method) properties of newly synthesized compound using smile codes were performed in detail.

Brammer L., Peuronen A., Roseveare T.M.

We report here on the status of research on halogen bonds and other σ-hole interactions involving p-block elements in Lewis acidic roles, such as chalcogen bonds, pnictogen bonds and tetrel bonds. A brief overview of the available literature in this area is provided via a survey of the many review articles that address this field. Our focus has been to collect together most review articles published since 2013 to provide an easy entry into the extensive literature in this area. A snapshot of current research in the area is provided by an introduction to the virtual special issue compiled in this journal, comprising 11 articles and entitled `Halogen, chalcogen, pnictogen and tetrel bonds: structural chemistry and beyond.'