Synthesis of Metalorganic Copolymers Containing Various Contorted Units and Iron(II) Clathrochelates with Lateral Butyl Chains: Conspicuous Adsorbents of Lithium Ions and Methylene Blue.

We report the synthesis of three highly soluble metalorganic copolymers, TCP1-3, that were made from a one-pot complexation of iron(II) clathrochelate units that are interconnected by various thioether-containing contorted groups. TCP1-3 were converted into their poly(vinyl sulfone) derivatives OTCP1-3 quantitatively via the selective oxidation of the thioether moieties into their respective sulfones. All of the copolymers, TCP1-3 and OTCP1-3, underwent structural analysis by various techniques; namely, 1H- and 13C-nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and gel permeation chromatography (GPC). The copolymers were tested as potent lithium ions adsorbents revealing a maximum adsorption (qm) value of 2.31 mg g-1 for OTCP2. Furthermore, this same copolymer was found to be a promising adsorbent of methylene blue (MEB); an isothermal adsorption study divulged that OTCP2's uptake of MEB from an aqueous solution (following the Langmuir model) was, at maximum adsorption capacity, (qm) of 480.77 mg g-1; whereas the kinetic study divulged that the adsorption follows pseudo second-order kinetics with an equilibrium adsorption capacity (qe,cal) of 45.40 mg g-1.

Exploring Toxins for Hunting SARS-CoV-2 Main Protease Inhibitors: Molecular Docking, Molecular Dynamics, Pharmacokinetic Properties, and Reactome Study.

The main protease (Mpro) is a potential druggable target in SARS-CoV-2 replication. Herein, an in silico study was conducted to mine for Mpro inhibitors from toxin sources. A toxin and toxin-target database (T3DB) was virtually screened for inhibitor activity towards the Mpro enzyme utilizing molecular docking calculations. Promising toxins were subsequently characterized using a combination of molecular dynamics (MD) simulations and molecular mechanics-generalized Born surface area (MM-GBSA) binding energy estimations. According to the MM-GBSA binding energies over 200 ns MD simulations, three toxins-namely philanthotoxin (T3D2489), azaspiracid (T3D2672), and taziprinone (T3D2378)-demonstrated higher binding affinities against SARS-CoV-2 Mpro than the co-crystalized inhibitor XF7 with MM-GBSA binding energies of -58.9, -55.9, -50.1, and -43.7 kcal/mol, respectively. The molecular network analyses showed that philanthotoxin provides a ligand lead using the STRING database, which includes the biochemical top 20 signaling genes CTSB, CTSL, and CTSK. Ultimately, pathway enrichment analysis (PEA) and Reactome mining results revealed that philanthotoxin could prevent severe lung injury in COVID-19 patients through the remodeling of interleukins (IL-4 and IL-13) and the matrix metalloproteinases (MMPs). These findings have identified that philanthotoxin-a venom of the Egyptian solitary wasp-holds promise as a potential Mpro inhibitor and warrants further in vitro/in vivo validation.

Selective removal of toxic organic dyes using TrÓ§ger base-containing sulfone copolymers made from a metal-free thiol-yne click reaction followed by oxidation.

Three copolymers TCP1-3 bearing TrÓ§ger's base (TB) units intercalated with various thioether groups were synthesized using a catalyst-free thiol-yne click reaction. TCP1-3 display excellent solubility in common organic solvents allowing for their structural, and photophysical characterization. The thioether groups in TCP1-3 were selectively oxidized into their respective sulfone derivatives under mild oxidation reaction conditions affording the postmodified copolymers TCP4-6. Investigation of organic dye uptake from water by TCP1-6 proved their efficiency as selective adsorbents removing up to 100% of the cationic dye methylene blue (MEB) when compared to anionic dyes, such as Congo red (CR), methyl orange (MO) and methyl blue (MB). The sulfone-containing copolymers TCP4-6 display superior and faster MEB removal efficiencies with respect to their corresponding synthons TCP1-3.

Microwave-assisted efficient one-pot synthesis of N 2-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines.

An efficient one-pot synthesis of N 2-(tetrazol-5-yl)-6-aryl/heteroaryl-1,3,5-triazine-2,4-diamine derivatives was developed by reacting 5-amino-1,2,3,4-tetrazole with aromatic aldehydes and cyanamide in pyridine under controlled microwave heating with high yields. X-ray crystallography confirmed the structure of the obtained products.

Chemistry of Heterocyclic Five and Six Membered Enamino Nitriles and Enamino Esters.

Progress in the chemistry of cyclic enamino-nitriles based on the advanced synthetic methodologies is reported. Due to the recent accomplishment, it becomes possible to reactivate these molecules toward electrophiles, nucleophiles and as electron rich dienes in 2+3 dipolar additions and in 4+2 cycloadditions reactions. Synthesizing the poly functionalized 4H-pyrans and their fused derivatives is a fascinating field with a multitude of biological implications such as antitumor, cardiotonic, hepatoprotective, antihypertensive, antibronchitis, as well antifungal activity. This work was conducted with particular emphasis on reviewing the work done on the cyclic enamines since 1990 up till now in order to highlight in more details the synthetic pathways, interactions and the biological activities, Furthermore; we referred to the recent original data of our group contributions within this field.

Recent developments in utility of green multi-component reactions for the efficient synthesis of polysubstituted pyrans, thiopyrans, pyridines, and pyrazoles.

Developments made since 2010 in the utilization of multi-component reactions as green efficient methodologies for the synthesis of polysubstituted pyrans, thiopyrans, pyridines, and pyrazoles are reviewed and the mechanisms of these processes are discussed. Reference is made to classical older synthetic methods developed earlier in our laboratories.

Organobase-catalyzed three-component reactions for the synthesis of 4H-2-aminopyrans, condensed pyrans and polysubstituted benzenes.

Novel routes for the preparation of 2-amino-4H-pyran-3-carbonitrile 9, amino-arylbenzoic acid ester derivatives 13a,b, 2-aminotetrahydro-4H-chromene-3-carbonitrile 18, 3-amino-4-cyanotetrahydronaphthalene-2-carboxylic acid ester 26 and 4-amino-3,5-dicyanophthalic acid ester derivatives 37a-c were developed. The synthetic methods utilize one-pot reactions of acetylene carboxylic acid esters, α,ß-unsaturated nitriles and/or active methylenenitriles in the presence of L-proline or DABCO. Plausible mechanisms are suggested for the formation of the products. Finally, these compounds were used for the efficient synthesis of 6-amino-5-cyanonicotinic acid ester derivatives 31a,b, ethyl 4-amino-5H-pyrano[2,3-d]pyrimidine-6-carboxylates 33a,b, 4-amino-6H-pyrrolo[3,4-g]quinazoline-9-carbonitrile 39, and 1,7-diamino-6-(N'-hydroxycarbamimidoyl)-3-oxo-5-phenyl-3H-isoindole-4-carboxylate (40).

Unexpected behavior of enaminones: interesting new routes to 1,6-naphthyridines, 2-oxopyrrolidines and pyrano[4,3,2-de][1,6]naphthyridines.

Reaction of enaminones 1a-d with 2-aminoprop-1-ene-1,1,3-tricarbonitrile (2) in the presence of AcOH/NH4OAc afforded 7-amino-5-oxo-5,6-dihydro-1,6-naphthyridine-8-carbonitrile derivatives 9a-d. On the other hand, 2-aminopyrano[4,3,2-de] [1,6]naphthyridine-3-carbonitriles 20a-c,e were the only obtained products from the reactions of 1a-d with 2 in the presence of AcOH/NaOAc, while 1d afforded [3,5-bis-(4-chloro-benzoyl)-phenyl]-(4-chloro-phenyl)-methanone 21 under the same condition. The reaction of 2 with diethyl acetylenedicarboxylate in the presence of AcOH/NH4OAc afforded (4-cyano-5-dicyanomethylene-2-oxo-2,5-dihydro-1H-pyrrol-3-yl)-acetic acid ethyl ester 15B.

Scope and limitations of a novel synthesis of 3-arylazonicotinates.

The reaction of 3-oxo-3-phenyl-2-phenylhydrazonal with functionally substituted and heteroaromatic substituted acetonitrile to yield arylazonicotinic acid derivatives and 5-arylsubstituted pyridines was established. In some cases the produced nicotinates could not be isolated as they underwent thermally induced 6π-electrocyclization yielding polynuclear pyridine derivatives.

Regioselectivity in the multicomponent reaction of 5-aminopyrazoles, cyclic 1,3-diketones and dimethylformamide dimethylacetal under controlled microwave heating.

The multicomponent reaction of 5-aminopyrazole derivatives with cyclic 1,3-dicarbonyl compounds and dimethylformamide dimethylacetal (DMFDMA) in DMF at 150 °C under controlled microwave heating afforded regioselectively 8,9-dihydropyrazolo[1,5-a]quinazolin-6(7H)-ones 6 rather than the corresponding dihydropyrazolo[5,1-b]quinazolin-8(5H)-ones 4.

Reassignment of the structures of products produced by reactions of the product believed to be 2-(1-phenyl-2-thiocyanatoethylidene)-malononitrile with electrophiles.

The reactivity of the product believed to be 2-(1-phenyl-2-thiocyanato-ethylidene)malononitrile toward a variety of electrophilic and nucleophilic reagents is reported.

Polyfunctional nitriles in organic syntheses: a novel route to aminopyrroles, pyridazines and pyrazolo[3,4-c]pyridazines.

Phenacylmalononitrile 1 reacts with dimethylformamide dimethyl acetal to yield an enaminone which could be readily converted into a pyrrole or an aminopyridazine by treating with ammonium acetate and hydrazine hydrate, respectively. Compound 1 reacted with hydrazine hydrate in ethanol at room temperature to yield the dihydropyridazine 9 as a single product. In refluxing ethanol this product further reacted with hydrazine hydrate to yield the novel dihydropyrazolopyridazinamine 10.