Catalyst- and solvent-free regiospecific SAr phosphinylation of pyridines with -phosphinates mediated by benzoylphenylacetylene.

Pyridines undergo a facile SAr phosphinylation with -phosphinates under catalyst- and solvent-free conditions (50-55 °C) in the presence of benzoylphenylacetylene to afford 4-phosphinylpyridines in up to 68% yield. In this reaction, benzoylphenylacetylene activates the pyridine ring by the formation of a 1,3(4)-dipolar complex, deprotonates -phosphinates to generate P-centered anions and finally acts as an oxidizer, being eliminated from an intermediate ion pair. Terminal electron-deficient acetylenes (methyl propiolate and benzoylacetylene) are inefficient as mediators in the above SAr process.

Iodine-Catalyzed Radical C-H Amination of Nonaromatic Imidazole Oxides: Access to Cyclic α-Aminonitrones.

A straightforward cross-dehydrogenative coupling approach to incorporate alicyclic amino residues into the structure of model cyclic aldonitrones, 2-imidazole oxides, is reported. The elaborated C(sp)-H functionalization is achieved by employing cyclic amines in the presence of the I--butyl hydroperoxide (TBHP) reagent system. As a result, a series of 19 novel heterocyclic derivatives were obtained in yields of up to 97%.

Novel Substituted Azoloazines with Anticoagulant Activity.

Hypercytokinemia, or cytokine storm, often complicates the treatment of viral and bacterial infections, including COVID-19, leading to the risk of thrombosis. However, the use of currently available direct anticoagulants for the treatment of COVID-19 patients is limited due to safety reasons. Therefore, the development of new anticoagulants remains an urgent task for organic and medicinal chemistry.

Mechanosynthesis of Polyureas and Studies of Their Responses to Anions.

Polyureas (PUs) have already found wide practical applications, and various methods of their synthesis have been reported. In this manuscript, we wished to report the very first mechanochemical approach towards aromatic PUs via reactions between isomeric 2,2'-, 3,3'-, and 4,4'-diaminobiphenyls and triphosgene under solvent-free conditions following ball-milling. By using this synthetic approach, both PUs and azomethine-capped Pus were obtained.

Recent Trends in the Antidiabetic Prominence of Natural and Synthetic Analogues of Aurones.

Natural products are a boundless source for the development of pharmaceutical agents against a wide range of human diseases. Accordingly, naturally occurring aurones possess various biological benefits, such as anticancer, antioxidant, antimicrobial, antidiabetic, anti-inflammatory, antiviral and neuroprotective effects. In addition, various studies have revealed that aurones are potential templates for the regulation of diabetes mellitus and its associated complications.

Polymers and Polymer-Based Materials for the Detection of (Nitro-)explosives.

Methods for the remote detection of warfare agents and explosives have been in high demand in recent times. Among the several detection methods, fluorescence methods appear to be more convenient due to their low cost, simple operation, fast response time, and naked-eye-visible sensory response. For fluorescence methods, a large variety of fluorescent materials, such as small-molecule-based fluorophores, aggregation-induced emission fluorophores/materials, and supramolecular systems, have been reported in the literature.

(1-(4-(5-Phenyl-1,3,4-oxadiazol-2-yl)phenyl)-1-1,2,3-triazol-4-yl)-methylenyls α,ω-Bisfunctionalized 3- and 4-PEG: Synthesis and Photophysical Studies.

Two new azaheterocycle-based bolas, such as (1-(4-(5-phenyl-1,3,4-oxadiazol-2-yl)phenyl)-1-1,2,3-triazol-4-yl)-methylenyls α,ω-bisfunctionalized PEGs, were prepared via Cu-catalyzed click reaction between 2-(4-azidophenyl)-5-(aryl)-oxadiazole-1,3,4 and terminal ethynyls derived from PEG-3 and PEG-4. Due to the presence of two heteroaromatic cores and a PEG linker, these bola molecules are considered as promising fluorescent chemosensors for electron-deficient species. As a result of a well-pronounced "turn-off" fluorescence response towards common nitro-explosive components, such as 2,4-dinitrotoluene (DNT) and 2,4,6-trinitrotoluene (TNT), hard-to-detect pentaerythritol tetranitrate (PETN), as well as Hg cation was observed.

TM-Free and TM-Catalyzed Mechanosynthesis of Functional Polymers.

Mechanochemically induced methods are commonly used for the depolymerization of polymers, including plastic and agricultural wastes. So far, these methods have rarely been used for polymer synthesis. Compared to conventional polymerization in solutions, mechanochemical polymerization offers numerous advantages such as less or no solvent consumption, the accessibility of novel structures, the inclusion of co-polymers and post-modified polymers, and, most importantly, the avoidance of problems posed by low monomer/oligomer solubility and fast precipitation during polymerization.

5-Amino-2-aryl-2H-1,2,3-triazole-4-carboxamides: Unique AIEE-gens and selective Hg fluorosensors.

A series of fluorescent sensors based on small molecule were designed and fully characterised, demonstrating AIEE effect and revealing an outstanding ability to selectively detect Hg ions. The structural and electronic properties were studied through quantum chemical calculations at (Time-Dependent) Density Functional Theory ((TD)-DFT) level. Carboxamides of 2-Aryl-1,2,3-Triazoles (CATs) showed significant differences in their photophysical properties depending on the structure of the substituent at amino function on the C5-atom in the heterocycle.

Antioxidants: Structure-activity of plant polyphenolics.

The excessive accumulation of reactive oxygen species (ROS)/free radicals can lead to abnormal oxidation of biomolecules such as proteins, lipids, fats, carbohydrates and nucleic acids in human organisms. Accordingly, endogenous oxidative stress induces the progressive development of various chronic diseases like rheumatoid arthritis, cancers, cardiovascular risks, diabetes, digestive ulcers, hypertension, obesity, neurological disorders, and age-related complications. Therefore, anti-oxidant defense mechanisms are needed to control/prevent the unbalanced molecular oxidative damage.

Biocompatible Silica-Polyethylene Glycol-Based Composites for Immobilization of Microbial Cells by Sol-Gel Synthesis.

Biocatalysts based on the methylotrophic yeast VKM Y-2559 immobilized in polymer-based nanocomposites for the treatment of methanol-containing wastewater were developed. The organosilica composites with different matrix-to-filler ratios derived from TEOS/MTES in the presence of PEG (SP-composite) and from silicon-polyethylene glycol (STP-composite) differ in the structure of the silicate phase and its distribution in the composite matrix. Methods of fluorescent and scanning microscopy first confirmed the formation of an organosilica shell around living yeast cells during sol-gel bio-STP-composite synthesis.

Amino Derivatives of Diaryl Pyrimidines and Azolopyrimidines as Protective Agents against LPS-Induced Acute Lung Injury.

The problem of lung damage originating from excessive inflammation and cytokine release during various types of infections remains relevant and stimulates the search for highly effective and safe drugs. The biological activity of the latter may be associated with the regulation of hyperactivation of certain immune cells and enzymes. Here, we propose the design and synthesis of amino derivatives of 4,6- and 5,7-diaryl substituted pyrimidines and [1,2,4]triazolo[1,5-]pyrimidines as promising double-acting pharmacophores inhibiting IL-6 and NO.

Comparison of Photophysical Properties of Lanthanide(III) Complexes of DTTA- or DO3A-Appended Aryl-2,2'-Bipyridines.

New Tb(III) and Eu(III) complexes based on aryl-2,2'-bipyridine ligands with a cyclic DO3A chelating unit appended in the alpha position of the bipyridine core were synthesized. The photophysical properties of these complexes were compared with those of complexes of ligands with identical aryl-2,2'-bipyridine chromophores, but with an acyclic DTTA residue as an additional chelating site in the alpha position of the bipyridine core. The nature of the polyaminocarboxylic acid fragments was found to have a significant influence on the luminescence.

4-Hydroxy-3-nitro-1,4-dihydrotriazolo[5,1-][1,2,4]triazines: synthesis, antiviral activity, and electrochemical characteristics.

A new method for preparation of 4-hydroxy-3-nitro-1,4-dihydrotriazolo[5,1-][1,2,4]-triazines using 1-nitro-2-morpholinoethylene and 3-diazo-1,2,4-triazoles is proposed. Antiviral activity against the Coxsackie B3 virus and electrochemical transformations of the prepared compounds are studied.

Mechanochemical Approach towards Multi-Functionalized 1,2,3-Triazoles and Anti-Seizure Drug Rufinamide Analogs Using Copper Beads.

Highly regiospecific, copper-salt-free and neat conditions have been demonstrated for the 1,3-dipolar azide-alkyne cycloaddition (AAC) reactions under mechanochemical conditions. A group of structurally challenging alkynes and heterocyclic derivatives was efficiently implemented to achieve highly functionalized 1,4-disubstituted-1,2,3-triazoles in good to excellent yield by using the Cu beads without generation of unwanted byproducts. Furthermore, the high-speed ball milling (HSBM) strategy has also been extended to the synthesis of the commercially available pharmaceutical agent, Rufinamide, an antiepileptic drug (AED) and its analogues.

Push-Pull Structures Based on 2-Aryl/thienyl Substituted Quinazolin-4(3)-ones and 4-Cyanoquinazolines.

Design and synthesis of 2-(aryl/thiophen-2-yl)quinazolin-4(3)-ones and 4-cyano-2-arylquinazolines with EtN-, PhN- or carbazol-9-yl- electron donating fragment are described. The key photophysical properties of these compounds have been studied by UV/Vis absorption and fluorescence spectroscopy in solvents of different polarity (toluene and MeCN). 2-(Aryl/thiophen-2-yl)quinazolin-4(3)-ones show fluorescence in blue-green region in toluene solution with quantum yields up to 89% in the case of 2-(4'-N,N-diphenylamino[1,1'-biphenyl]-4-yl)-quinazolin-4(3)-one.

An insight from computational approach to explore novel, high-affinity phosphodiesterase 10A inhibitors for neurological disorders.

The enzyme Phosphodiesterase 10A (PDE10A) plays a regulatory role in the cAMP/protein kinase A (PKA) signaling pathway by means of hydrolyzing cAMP and cGMP. PDE10A emerges as a relevant pharmacological drug target for neurological conditions such as psychosis, schizophrenia, Parkinson's, Huntington's disease, and other memory-related disorders. In the current study, we subjected a set of 1,2,3-triazoles to be explored as PDE10A inhibitors using diverse computational approaches, including molecular docking, classical molecular dynamics (MD) simulations, Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) calculations, steered MD, and umbrella sampling simulations.

Mechanism, Kinetics and Thermodynamics of Decomposition for High Energy Derivatives of [1,2,4]Triazolo[4,3-][1,2,4,5]tetrazine.

This paper presents the data of research studies on the mechanisms, kinetics and thermodynamics of decomposition of three high-energy compounds: [1,2,4]triazolo[4,3-][1,2,4,5]tetrazine-3,6-diamine (TTDA), 3-amino-6-hydrazino[1,2,4]triazolo[4,3-][1,2,4,5]tetrazine (TTGA) and 3,6-dinitroamino[1,2,4]triazolo[4,3-][1,2,4,5]tetrazine (DNTT). The points of change of the reaction mechanisms under thermal effects with different intensities from 0.1 to 2000 s have been established.

Synthesis and Photophysical Properties of α-(-Biphenyl)-Substituted 2,2'-Bipyridine-Based Push-Pull Fluorophores.

A series of new α-(-biphenyl)-substituted 2,2'-bipyridines were obtained through the combination of the ipso-nucleophilic aromatic substitution of the C5-cyano group, aza-Diels-Alder and Suzuki cross-coupling reactions, starting from 5-cyano-1,2,4-triazines. For the obtained compounds, photophysical and fluorosolvatochromic properties were studied. Fluorophores and demonstrated unexpected AIEE activity, while and showed promising nitroexplosive detection abilities.

The Effect of the Stress State, Testing Temperature, and Hardener Composition on the Strength of an AlMg5/Epoxy Metal-Polymer Joint.

The regularities of the effect of a complex stress state on the strength of an AlMg5/epoxy adhesive joint are experimentally studied at -50 and +23 °C in tension+shear and compression+shear tests with different normal-to-shear stress ratios. The tests use modified Arcan specimens and Brazil-nut-sandwich specimens, with the lateral faces of the adhesive layer having a shape of a mushroom-like "ridge" aimed at reducing stress concentration at the specimen edges. An original computational model of a selected microvolume including the interface together with the adjacent substrate and adhesive layers is used to process the experimental results.

Facile synthesis of 6-organyl-4-(trifluoromethyl)pyridin-2(1)-ones and their polyfluoroalkyl-containing analogs.

The three-component cyclization of 3-polyfluoroalkyl-3-oxopropanoates and methyl ketones with ammonium acetate affords 6-organyl-4-(polyfluoroalkyl)pyridin-2(1)-ones (organyl is alkyl, aryl, or hetaryl). The synthesized pyridones were evaluated for antifungal, antibacterial, and analgesic activity.

Sustainable Solvent-Free Diels-Alder Approaches in the Development of Constructive Heterocycles and Functionalized Materials: A Review.

The Diels-Alder reaction (DAR) is found in myriad applications in organic synthesis and medicinal chemistry for drug development, as it is the method of choice for the expedient synthesis of complex natural compounds and innovative materials including nanomaterials, graphene expanses, and polymeric nanofibers. Furthermore, the greatest focus of attention of DARs is on the consistent reaction procedure with stimulus yields by highly stereo- and regioselective mechanistic pathways. Therefore, the present review is intended to summarize conventional solvent-free (SF) DARs for the expedient synthesis of heterocyclic compounds and materials.

Benchmarking the ability of novel compounds to inhibit SARS-CoV-2 main protease using steered molecular dynamics simulations.

Background: The SARS-CoV-2 main protease (M) is an attractive target in the COVID-19 drug development process. It catalyzes the polyprotein's translation from viral RNA and specifies a particular cleavage site. Due to the absence of identical cleavage specificity in human cell proteases, targeting M with chemical compounds can obstruct the replication of the virus.

Assessment on facile Diels-Alder approach of α-pyrone and terpenoquinone for the expedient synthesis of various natural scaffolds.

The development of highly facile synthetic procedures for the expedient synthesis of complex natural molecules is always in demand. As this aspect, the Diels-Alder reaction (DAR) has a versatile approach to the synthesis of complex natural compounds and highly regio-/stereoselcetive heterocyclic scaffolds. Additionally, α-pyrone and terpenoquinone are two versatile key intermediates that are prevalent in various bioactive natural compounds for instance, (±)-crinine, (±)-joubertinamine, (±)-pancratistatin, (-)-cyclozonarone, and 8-ephipuupehedione, etc.