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The current viral pandemic, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), creates health, mental, economic, and other serious challenges that are better to say global crisis. Despite the existence of successful vaccines, the possible mutations which can lead to the born of novel and possibly more dangerous variants of the virus as well as the absence of definitive treatment for this potentially fatal multiple-organ infection in critically ill patients make us keep searching. Theoretically targeting human and viral receptors and enzymes via molecular docking and dynamics simulations can be considered a wise, rational, and efficient way to develop therapeutic agents against COVID-19. In this way, The RNA-dependent RNA polymerase (RdRP), main protease, and spike glycoprotein of SARS-CoV-2 as well as the human angiotensin-converting enzyme 2 receptor and transmembrane serine protease 2 are the most discussed and studied targets that play essential roles in the viral life and infection cycle. In the current in silico investigation, the guanidine functionality containing drugs and medicinal substances such as metformin, famotidine, neuraminidase inhibitors, antimalarial medications, anticancer drug imatinib, CGP compounds, and human serine protease inhibitor camostat were studied against the above-mentioned therapeutic targets and most of them (especially imatinib) have revealed an incredible spectrum of free docking scores and MD results. The current in silico investigation that its novel perspective of view is corroborated by the different experimental and clinical evaluations, confirms that the guanidine moiety can be considered as a missing promising pharmacophore in drug design and development approaches against SARS-CoV-2. Considering the chemical potency of this polyamine group in chemical interaction creation, the observed outcomes in this virtual screening were not surprising. On the other hand, the guanidine functional group has unique physico-chemical properties such as basicity that can make the target cells intracellular pH undesirable for the virus entry, uncoating, and cytosolic lifecycle. According to the obtained results in the current study that are interestingly confirmed by the previously reported efficacy of some the guanidine carrying drugs in COVID-19, guanidine as a potential multi-target anti-SARS-CoV-2 functional scaffold deserves further comprehensive investigations.The online version contains supplementary material available at 10.1007/s11696-022-02528-y.

An efficient, green, one-pot, and three-component protocol has been reported for the stereoselective synthesis of a new class of spiro thiazolidines. A series of spiro-heterocycle derivatives were produced stereoselectively in high yields by the reaction of 5-arylidene thiazolidine-2,4-diones, isatin, and secondary amino acids in the presence of MnCoCuFe2O4@L-proline (MCCFe2O4@L-proline) magnetic nanorods as a novel nanocatalyst. The synthesized catalyst was fully characterized for thermal stability, magnetic properties, and other physicochemical properties via numerous techniques. It was applied as an efficient and reusable catalyst for the synthesis of endo-isomers of spirocyclic pyrrolidine/pyrrolizidine/pyrrolothiazolidine derivatives in high yield. The regioselectivity and stereochemistry of these heterocyclic spiro-compounds were established by 1H, 13C, HMBC, HSQC, and COSY NMR spectroscopy techniques. The main attractive characteristics of the presented protocol are high yield, high level of diastereoselectivity, and easy recovery of catalyst without significant loss of its catalytic activity.

A novel fluorescent chemosensor calix[4]arene L, containing two fluorogenic coumarin units at the lower rim has been synthesized via click reaction. The structure of this chemosensor, was characterized by IR, NMR spectra and elemental analysis. Ion-binding properties of L were investigated in acetonitrile with different metal ions and the recognition process was monitored by fluorescence, UV-Vis and 1H NMR spectral changes. In comparison with other metal ions, chemosensor L showed a specific selectivity toward copper ions‏. The Job plot analysis revealed that the binding between L with Cu2+ is in 1:1 stoichiometry. The association constant (Ka) for the complex L.Cu2+ was found to be 1.6 × 105 M−1. The limit of detection of the sensor L was determined to be 5.4 × 10−7 M. This sensitive and selective chemosensor was successfully applied for the detection of Cu2+ ions in human blood serum with 90–100% recovery.

Using density functional theory calculations, we investigated the potential application of Al12N12 and B12N12 nanoclusters as an electronic or work function type sensor for acetylsalicylic acid (ASA) drug detection. The drug tends to be adsorbed on the surface of both AlN and BN clusters via its –COOH group with adsorption energies about − 62.8 and − 21.9 kcal/mol, respectively. The AlN nanocluster is neither electronic nor work function based sensor for ASA because of a low sensitivity, and a huge recovery time (~ 9.8 × 1038 s). But the response of BN nanocluster is completely different, and its electrical conductivity is largely increased in the presence of ASA drug due to the large stabilization of LUMO level. We concluded that the BN nanocluster may be a promising candidate to detect the ASA drug with a short recovery time about 109 s and a high electronic sensitivity. As the work function of the BN nanocluster is not affected by the ASA adsorption, it cannot be used as a work function type sensor.

Cathinone (CT) is a psychoactive drug which its abuse is linked to several deaths worldwide. Here, we investigated the electronic response of BC 2 N nanotubes to the CT drug, using density functional theory calculations. Our results indicate that the CT drug is adsorbed on the pristine tube from its –NH 2 group with ad adsorption energy about −14.6 kcal/mol with no electronic response. To overcome this problem, we doped the tube with Al or Si atom. Both of the Al and Si dopants increase the tube sensitivity and strengthen the interaction. Our calculations demonstrate that despite the high sensitivity of the Al-doped BC 2 N nanotube to the CT drug, it suffers from a very long recovery time which makes it unsuitable for application in CT sensors. But the calculated recovery time for the Si-doped BC 2 N nanotube is predicted to be about 0.27 s , which is short and desirable. Also, we showed that the Si-doped tube can be used in the humidity condition and at the presence of some gases including H 2 , O 2 , N 2 , and CO 2 . It was concluded that Si-doped BC 2 N nanotubes may be promising candidate for application in the CT sensors which benefit form a short recovery time, high sensitivity, and selectivity.

Cathinone is an organic stimulant which is classified as psychoactive drug and its abuse has been linked to many deaths worldwide. Here, we studied the electronic sensitivity of a BN cage, a zigzag (6, 0) BN nanotube, and a BN nanosheet toward cathinone using density functional theory calculations. The B3LYP-D functional predicts that the order of magnitude of electrical conductivity of BN nanostructures is as follows tube > sheet > cage. The cathinone drug prefers to be adsorbed on the BN nanostructures via its NH2 group rather than O-head with adsorption energy about −16.1, −14.0 and −5.0 kcal/mol for cage, tube, and sheet, respectively. Our results indicate that by increasing the p-character of the hybridization of the adsorbing B atom in the BN nanostructures, the interaction is strengthened. Based on the density of states analysis, it was demonstrated that the electrical conductivity of the BN nanostructures is decreased by the drug adsorption, indicating that they can be used in the cathinone sensors. The order of magnitude of the sensitivity is as follows: SCage > STube > SSheet. This trend corresponds to the decrease of the structural curvature in the BN nanostructures. Finally, a short recovery time of about 0.54 s, 0.02 s and 4.4 ns is predicted for cage, tube and sheet, respectively, at 298 K.

Penetration of most of the polar drugs through the cell membrane is a challenging problem. It has been indicated that carbonaceous nanostructures can penetrate into biological cells. Here, we investigated the potential application of a C24 fullerene as a carrier for anti-cancer 5-fluorouracil (5-FU) drug using density functional theory calculations. It was found that the 5-FU interaction with the pristine fullerene is very weak with adsorption energy of about −3.2 kcal/mol which is not suitable for drug delivery. To overcome this problem, one carbon atom is substituted by a boron atom which increases the adsorption energy to −27.2 kcal/mol. The B-doping makes the electronic properties of the fullerene sensitive to the drug. Finally, we proposed a drug release based on the low pH in the cancer cells. It was indicated that attacking protons to the interaction area between the drug and fullerene separates the drug from the carrier.

The electronic, optical, energetic, and structural properties of a HBC (hexa-peri-hexabenzocoronene) nanographene and its central benzene- and coronene-like BN substituted forms, and also full BN analogue were investigated using density functional theory. It was found that a larger number of carbon atoms cause a more negative cohesive energy and, thereby a greater structural stability. Our nucleus independent chemical shift analysis indicates that the aromaticity and Clar’s sextet rule determine the relative stability of these structures. The benzene-like or coronene-like doping makes the HBC more insulator or semiconductor. Electron-hole Frenkel type exciton binding energy was predicted and calculated to be nearly identical for all nanographenes in the range of 0.61–0.69 eV. The coronene-like BN-doped HBC (BN2-HBN) shows higher conductivity due to very narrow optical and HOMO-LUMO energy gap. Partial density of states analysis indicates that the BN2-HBC electronically can be assumed a full BN whose peripheral atoms are replaced by carbon atoms. These carbon atoms are responsible for new states which are appeared within the gap.

Imidazole and its derivatives are privileged N-heterocyclic structures present in various natural products and synthetic pharmaceuticals. Despite the numerous methods that have been developed for the synthesis of imidazole cores, it is still challenging to readily achieve high efficiency and regioselectivity in imidazole synthesis. Therefore, synthesis of these compounds using new protocols is always interesting. In this study we discuss the most representative and interesting reports on the synthesis of imidazoles and their fused analogues from N-propargylamines. Mechanistic aspects of the reactions are considered and discussed in detail.

3-Methyleneindolinone derivatives are important structural motifs found in many compounds of natural occurrence and pharmacological significance. However, despite their wide importance, mild and highly efficient stereoselective synthesis of (E)- and (Z)-3-methyleneindolinones still remains to be a difficult problem. Therefore, the development of new synthetic methods for their stereocontrolled preparation is of prime importance in organic synthesis. In this mini review, we highlight the advances in stereoselective synthesis of mono- and disubstituted-3-methyleneindolinones through metal-catalyzed intramolecular cyclization of N-arylpropiolamides from 1988 to 2017.

Natural phosphate was applied as an efficient and ecofriendly catalyst for the synthesis of tetraketones (2–2.5 h, 90–100 %) and xanthenes (6.5–8.5 h, 84–95 %) via Knoevenagel–Michael cascade reaction of aromatic aldehydes with 1,3-cyclic diketones in water and ethanol, respectively. This protocol provides several advantages over the traditional chemical synthesis, such as simple work-up, easy handling procedure, non-toxicity and stability of catalyst, low cost and environmental friendliness.

This review article is an attempt to survey literature describing synthetic methods in the preparation of quinoline derivatives from N-propargylamines. Mechanistic aspects of the reactions are considered and discussed in detail.

N-Propargylamines are one of the most useful and versatile building blocks in organic synthesis that are successfully transformed into many significant N-heterocycles. Due to high atom economy and shorter synthetic routes, the synthesis of 1,4-oxazepane and 1,4-diazepane cores from N-propargylamines have undergone an explosive growth in recent years. This review gives an overview of new developments in the synthesis of the title compounds from N-propargylamines in recent years. Mechanistic aspects of the reactions are considered and discussed in detail.

The pyridine is one of the simplest, yet most important N-heterocycles. This ring is utilized in more than 100 drugs and this number is increasing by the day. Therefore, synthesis of these compounds using new protocols is always interesting. This review surveys research work on the preparation of pyridines and their ring fused analogues from N-propargylamines. In this review, we have classified these reactions based on the type and the desired products.

A novel chemiluminescence (CL) method using water-soluble Mn-doped ZnS quantum dots (QDs) as sensitizers is proposed for the chemiluminometric determination of atropine in pharmaceutical formulation. Water-soluble Mn-doped ZnS QDs were synthesized by using l -cysteine as stabilizer in aqueous solutions. The nanoparticles were structurally and optically characterized by X-ray powder diffraction (XRD), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), UV–vis absorption spectroscopy and photoluminescence (PL) emission spectroscopy. It was found that ZnS quantum dots acted as enhancers of the weak CL emission produced upon oxidation of sulfite by Ce(IV) in acidic medium. Trace amounts of atropine improved the sensitize effect of ZnS quantum dots yielding a significant chemiluminescence enhancement of the Ce(IV)–SO 3 2− –ZnS QD system. Therefore, a new CL analysis system was developed for the determination of atropine. Under the optimum conditions, there is a good linear relationship between the relative chemiluminescence intensity and the concentration of atropine in the range of 1×10 −9 –1×10 −6 M of atropine with a correlation coefficient ( R 2 ) of 0.9992. The limit of detection of this system was found to be 2.54×10 −10 M. This method is not only simple, sensitive and low cost, but also reliable for practical applications.

A macromonomer, 1,3-bis[(2-hydroxy-3-acrylate)propyloxy]2-hydroxypropane (BHAPP) was prepared by the reaction of acrylic acid with diglycerol diglycidyl ether (DGE) in the presence of triethyl amine as a catalyst. The progress of the reaction was followed by measuring the decrease in intensity of the epoxide absorption peak at 915 cm−1, and structure of BHAPP was characterized by FTIR and 1H NMR spectroscopy. The effect of nanosilica (NS) particles as catalyst on thermal and photocuring of BHAPP was studied. The photopolymerization was carried out with the visible light using camphorquinone and N,N-dimethylaminoethylmethacrylate (DMAEM) as the photoinitiating system. The kinetic parameters of thermal curing were obtained using nonisothermal differential scanning calorimeter (DSC), and the data indicated that NS particles catalyzed the cure reaction by shifting the exothermic peak toward lower temperatures, decreasing the activation energy (E a), and increasing the rate constant value. The absorption properties of the cured nanocomposites were also studied in different exposure conditions.

To investigate the base pair binding probabilities for nucleic acid bases, numerous models were studied for contacts between adenine, thymine, guanine, cytosine, and uracil using density functional theory (DFT) in combination with the 6–311G* basis set. We obtained an assessment for the energy given by our calculations in gas and aqueous phases, which showed that it should be incorporated into hydrogen bonding and propeller rotational energies. The 42 complexes of base pairs (5 regular and 37 irregular base pairs) were proposed and their hydrogen-bonding (H-bonding) properties were verified. The hydrogen bonds in some irregular base pairs, including CC, UU, and TT (series 1), were stronger than in regular GC and AT base pairs. Also, the strength of the hydrogen bonds in the proposed base pairs, including CU, GG, GU, and TU (series 2), were similar to regular base pairs from an energetic point of view. The propeller rotations revealed a higher rotational barrier energy (6–7.5 kcal/mol; 1 cal = 4.184 J) for irregular base pairs (series 1 and 2) than regular GC and AT ones (1–3 kcal/mol). Nevertheless, the trend in these affinities of the complex contact probabilities and their biological properties were confirmed by our calculations.

A DFT calculations are carried out at UB3LYP/6-311++G (3df, 2p) levels of theory to study electrocyclic thermal cleavage of four (R) derivatives of unsaturated bicyclic diaziridines, 1X-R, to produce corresponding (Z) and (E) azomethine imides (2X-Z, 2X-E, 3X-Z and 3X-E), where X=H, Me, t-Bu and Ph. Cleavage of 1X-Rseries to form the most stable 3X-Zproduct, (path 2) is found the favored procedure because of delocalized negative charge on five atoms and lower steric effect in related transition state. According to IRC calculations in paths 1 and 2, C6N1 bond is cleaved before the rate determinating step (transition state). The stability of unsaturated bicyclic diaziridines and their corresponding (Z) and (E) azomethine imides is in the following order in gas phase and chloroform, tetrahydrofuran, and acetone solvents: 3X-Z

Conformational analysis and frequency calculation were achieved for 1-phenyl-1,2-propandione 1-oxime and its four tautomers: 1-nitroso-1-phenyl-1-propen-2-ol, 1-nitroso-1-phenyl-2-propanone, 2-hydroxy-1-phenyl-propenone oxime, and 3-nitroso-3-phenyl-propen-2-ol. Calculations were carried out at the Hartree–Fock (HF), Density Functional Theory (B3LYP), and the second-order Moller–Plesset perturbation (MP2) levels of theory using 6-31G* and 6-311G** basis sets. Five conformers with no imaginary vibrational frequency were obtained by free rotations around three single bonds of 1-phenyl-1,2-propandione-1-oxime: Ph–C(NOH)C(O)CH3, PhC(NOH)–C(O)CH3, and PhC(N–OH)C(O)CH3. Similarly, eight structures with no imaginary vibrational frequency were encountered upon rotations around three single bonds of 1-nitroso-1-phenyl-1-propen-2-ol: Ph–C(NO)C(OH)CH3, PhC(N–O)C(OH)CH3, and PhC(NO)C(–OH)CH3. In the same manner, six minima were found through rotations around three single bonds of 1-nitroso-1-phenyl-2-propanone: Ph–CH(NO)C(O)CH3, PhCH(–NO)C(O)CH3, and PhCH(NO)–C(O)CH3. Also, two minima were found through rotations around four single bonds of 2-hydroxy-1-phenyl-propenone oxime: Ph–C(NOH)C(OH)CH2, PhC(N–OH)C(OH)CH2, PhC(NOH)–C(OH)CH2, and Ph-C(NOH)C(–OH)CH2. Finally, two minima were found through rotations around four single bonds of 3-nitroso-3-phenyl-propen-2-ol: Ph–CH(NO)C(OH)CH2, PhCH(–NO)C(OH)CH2, PhCH(NO)–C(OH)CH2, and PhCH(NO)C(–OH)CH2. Interconversions within the above sets of conformers were probed through scanning (one and/or two dimensional), and/or QST3 techniques. The order of the stability of global minima encountered was: 1,2-propandione-1-oxime > 1-nitroso-1-phenyl-2-propanone > 1-nitroso-1-phenyl-1-propen-2-ol > 2-hydroxy-1-phenyl-propenone oxime > 3-nitroso-3-phenyl-propen-2-ol. Hydrogen bonding appears significant in tautomers of 1-nitroso-1-phenyl-1-propen-2-ol and 2-hydroxy-1-phenyl-propenone oxime. The CIS simulated λmax for the first excited singlet state (S1) of 1-phenyl-1,2-propandione 1-oxime is 300.4 nm, which was comparable to its experimental λmax of 312.0 nm. The calculated IR spectra of 1-phenyl-1,2-propandione 1-oxime and its tautomers were compared to the experimental spectra.

An efficient and simple synthesis of α-hydroxyphosphonates via reaction of aldehydes and ketones with dimethylphosphite in the presence of MgCl2/Et3N base system is reported. The use of readily available and easy to handle reagent MgCl2/Et3N makes this method simple, convenient, and practical.

Efficient selective oxidation of primary, secondary, and benzylic alcohols to the corresponding carbonyl compounds by a new chromium oxidizing reagent, pyridinium-1-sulfonate fluorochromate, C5H5NSO3H [CrO3F] (PSFC) is reported. Various cholesterol derivatives were easily converted to related oxocholesterol from allylic oxidation at lower temperature in comparison to other general oxidants. This oxidation procedure is simple and affords good yields.

The synthesis of new methacrylate-based, curable macromonomers, 4,4′-bis[2-hydroxy-3-aminopropylmethacrylate] diphenyl ether (BHAPE) and 4,4′-bis[2-hydroxy-3-aminopropylmethacrylate] diphenyl methane (BHAPM), is reported. BHAPE and BHAPM were prepared by the reaction of glycidyl methacrylate (GMA) with 4,4′-diaminodiphenyl ether and 4,4′-diaminodiphenyl methane, respectively. The progress of the reaction was monitored by thin-layer chromatography (TLC), and the structure of the monomers was characterized by Fourier transform infrared (FTIR) and 1H-NMR spectroscopy. Thermal curing of the monomers was conducted in a differential scanning calorimeter (DSC) with peroxide as the initiator. Thermal curing of the monomers showed the highest rate at 100°C with the activation energy value in the range 80–90 kJ distilled/mol. The water absorption properties of the cured samples in water, acidic, and basic solutions were studied. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010