A new synthesis of biologically active pyrroles: Formal synthesis of pentabromopseudilin,bimetopyrol, and several antitubercular agents

Although pyrroles have been synthesized from azido dienes, the corresponding reactions of structurally similar nitrodienes had not been investigated until it became the main focus of this study. This article describes the synthesis of several biologically active pyrroles and mechanistically intriguing results in connection with our new approach using nitrodienes in the presence of Ph₃P and a Mo catalyst, bis (acetylaceto)dioxomolybdenum (VI). The final precursor of pentabromopseudilin (PBP), pseudilin, was synthesized in four steps from o-hydroxycinnamaldehyde. An alternate pathway to PBP proceeded through o-methylpseudilin, prepared in two steps from o-methoxycinnamaldehyde. Both starting materials are commercially available. Similarly, bimetopyrol (2-methyl-4,5-bis(p-methoxyphenyl)pyrrole), a potent anti-inflammatory, was prepared using the new methodology. The remarkable conversion of nitrodienes 14 and 15 to bimetopyrol highlights the formation of a nitroso or nitrene intermediate. We also established that 14 and 15 interconvert in the presence of ambient light and each converts to bimetopyrol when reacted separately. The wide application of our synthetic methodology includes preparation of several antitubercular and Herpes Simplex 2 (HSV2) agents.     

A new chromium (III) complex containing N-(2-pyridylmethyl)-2-pyrazinecarboxamide, (NPyPzCa): Synthesis,molecular and crystal structure and theoretical electron density analysis

The chromium (III) complex [Cr(NPyPzCa)Cl₂(H₂O)].(CH₃)₂O (1) (NPyPzCa stands for N-(2-pyridylmethyl)-2-pyrazinecarboxamide) has been synthesized and characterized by single crystal X-ray diffraction. The Cr(III) atom exhibits an octahedral geometry due to the coordination of three donor atoms from carboxamide ligand, two chlorine atoms and one water molecule. There is O–H?O hydrogen bonds and also π–π interactions between adjacent pyridine and ?pyrazine rings that seem to be effective in the stabilization of the crystal packing. The ?topological and energetic properties of the electron density distribution of all the metal–ligand ?bonding interactions in this complex have also been calculated and studied at ? several DFT levels. According to the results, metal–ligand bonding interactions belong (from the topological and energetic point of view) to new interactions that represent a mix of closed-shell (ionic) and shared (covalent) characters.     

Wall effects on electrophoretic motion of spherical polystyrene particles in a rectangular poly(dimethylsiloxane) microchannel

The wall effects on electrophoretic motion of spherical polystyrene particles in a rectangular poly(dimethylsiloxane) microchannel were studied experimentally. It is found that the particle electrophoretic velocity is insensitive to the trajectory between the channel sidewalls, consistent with the theoretical prediction. We also demonstrate that the electrophoretic motion of larger particles along the channel centerline is more viscously retarded by the sidewalls of a narrower channel. This observation is well predicted by incorporating the analytical models for the particle electrophoresis along the centerline of a slit channel and along the axis of a cylindrical pore.     

Confinement effects on the thermal stability of poly(ethylene oxide)/graphene nanocomposites: A reactive molecular dynamics simulation study

Nonisothermal and isothermal decomposition of poly(ethylene oxide) (PEO) loaded with different concentrations of pristine graphene (PG) and graphene oxide (GO) nanoplatelets were investigated using reactive molecular dynamics simulation. The onset of nonisothermal decomposition of the PG‐loaded PEO system was the highest among all systems, suggesting that introducing PG to the polymer improves its thermal stability (an effect that increases with an increase in the PG concentration). At low concentration, introducing GO to the polymer brings about a deterioration of the thermal stability of the polymer consistent with experimental findings. On average, the activation energy for the isothermal decomposition of PG‐loaded PEO system increases by 60% over that of the neat PEO system, while it decreases by 40% for the GO‐loaded PEO system. A time‐dependent analysis of the through‐thickness decomposition profile of the above systems reveals that the polymer confined between the PG sheets exhibit a higher thermal stability compared to the bulk polymer. However, an opposite effect is observed with the polymer confined between the GO sheets. The latter observation is attributed to accelerated polymer chain scission in confined regions due to the ejection of reactive hydroxyl radicals from the GO surface during the early stages of thermal decomposition. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017 , 55, 1026–1035     

Tandem Favorskii Intermediate/Cyclization Leading to Tricyclo[4.4.0.0]decanediones

The mechanism of dehydrobromination of the bromodiketone 8 leading to the unusual ring system of tricyclo[4.4.0.0]decanediones (9 and 10) is described. An entry into the ring system of the sesquiterpenoid hydrocarbons copaene and ylangene, 8 to 9, is achieved in three steps starting with enone 6. Compound 9 was either derived from a direct internal S_N2 cyclization of 8 or the Favorskii intermediate 8a. Formation of compound 10, on the other hand, can only occur via the Favorskii intermediate 8a. Structure assignments of 9 and 10 were determined using both one‐ and two‐dimensional NMR experiments.     

Suppression of Pulmonary Tumor Promotion and Induction of Apoptosis by <Emphasis Type="Italic">Crocus sativus</Emphasis> L. Extraction

Crocus sativus L., commonly known as saffron, is the raw material for one of the most expensive spice in the world, and it has been used in folk medicine for centuries. We investigated the potential of the ethanolic extract of saffron to induce cytotoxic and apoptosis effects in carcinomic human alveolar basal epithelial cells (A549), a commonly used cell culture system for in vitro studies on lung cancer. The cells were cultured in Dulbecco’s modified Eagle’s medium with 10% fetal bovine serum treated with different concentrations of the ethanolic extract of saffron for two consecutive days. Cell viability was quantitated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Apoptotic cells were determined using annexin V–fluorescein isothiocyanate by flow cytometry. Saffron could decrease the cell viability in the malignant cells as a concentration- and time-dependent manner. The IC₅₀ values against the A549 cell lines were determined as 1,200 and 650 μg/ml after 24 and 48 h, respectively. Saffron-induced apoptosis of the A549 cells in a concentration-dependent manner, as determined by flow cytometry histogram of treated cells that induced apoptotic cell death, is involved in the toxicity of saffron. It might be concluded that saffron could cause cell death in the A549 cells, in which apoptosis plays an important role. Saffron could also be considered as a promising chemotherapeutic agent in lung cancer treatment in future.     

Hybrid-DFT Study and NBO Analysis of the Stereoelectronic Interaction Effects (Associated with the Anomeric Effects) on the Conformational Properties of 2,3,5,6-Tetrahalo-1,4-dioxanes and Their Analogs Containing S and Se Atoms

NBO analysis and hybrid density functional theory–based method (B3LYP/6-311+G**) was used to study the anomeric effects (AE), dipole–dipole interactions, and steric repulsion effects on the conformational properties of 2,3,5,6-tetrahalo-1,4-dioxane [halo = F (1), Cl (2), Br (3)], 2,3,5,6-tetrahalo-1,4-dithiane [halo = F (4), Cl (5), Br (6)], and 2,3,5,6-etrahalo-1,4-diselenane [halo = F (7), Cl (8), Br (9)]. B3LYP/6-311+G** results revealed a strong axial preference in compounds 1–3. Gibbs free energy difference (G _eq–G _ax) values (e.g., ΔG _eq-ax) between the axial and equatorial conformations of compound 1 to compound 3 are 8.19, 3.86, and 3.13 kcal mol^?1, respectively, as calculated by the B3LYP/6-311+G** level of theory. On the other hand, the NBO analysis of donor–acceptor (bond–antibond) interactions revealed that the AE for compounds 1–3 are ?12.26, ?16.46, and ?18.11 kcal mol^?1, respectively. Contrary to the increase of the AE values from compound 1 to compound 3, the increase of the steric repulsions (e.g., 1,3-syn-axial repulsions) could fairly explain the decrease of the axial conformation stability in compounds 1–3 compared to their equatorial conformations. Further, the correlations between the AE, structural parameters, and conformational behavior of compounds 4–9 have been investigated.     

Resonance structure counts in contorted and flat hexabenzocoronenes

In several articles we have reported algorithms to count resonance structures for convex cyclofusenes and parallelogram-like benzenoids with and without holes using a combinatorial/geometric approach. In this article, using the same approach we report algorithms that facilitate resonance structure counts in both contorted and flat hexabenzocoronene.     

Substituted pyrrole synthesis from nitrodienes

Though the Cadogan-Sundberg approach has been employed to synthesize a variety of indole and carbazole derivatives from nitroarenes, surprisingly, very little is reported for making pyrroles using the same approach from non-arene nitrodienes. Herein, we report a general method to synthesize substituted pyrroles, in one step with modest yields, from nitrodienes using triphenylphosphine in the presence of an Mo catalyst, bis(acetylaceto)dioxomolybdenum (VI). To shed light on the mechanism of this reaction, we performed DFT calculations using uB3LYP/6-31+G(d) basis set and observed that the reaction favors a path through a nitrene intermediate.     

DNAzyme-embedded hyperbranched DNA dendrimers as signal amplifiers for colorimetric determination of nucleic acids

A DNAzyme-embedded hyperbranched DNA dendrimer is used as a colorimetric signal amplifier in an ultrasensitive detection scheme for nucleic acids. The hyperbranched DNA dendrimers were constructed by single-step autonomous self-assembly of three structure-free DNA monomers. A cascade of self-assembly reactions between the first and second strands leads to the formation of linear DNA concatemers containing overhang flank fragments. The third strand, which bears a peroxidase-mimicking DNAzyme domain, serves as a bridge to trigger self-assembly between the first and second strands across the side chain direction. This results in a chain branching growth of the DNAzyme-embedded DNA dendrimer. This signal amplifier was incorporated into the streptavidin-biotin detection system which comprises an adaptor oligonucleotide and a biotinylated capture probe. The resulting platform is capable of detecting a nucleic acid target with an LOD as low as 0.8 fM. Such sensitivity is comparable if not superior to most of the reported enzyme-free (and even enzyme-assisted) signal amplification strategies. The DNA dendrimer based method is expected to provide a universal platform for extraordinary signal enhancement in detecting other nucleic acid biomarkers by altering the respective sequences of adaptor and capture probe.

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Graphical abstract Schematic of an assembly of a DNAzyme-embedded hyperbranched DNA dendrimer which operates as a signal amplifier for nucleic acids detection. The nanostructure is constructed by autonomous self-assembly of three DNA monomers. Colored letters represent each domain, and complementary domains are marked by asterisk. Domain d represents the DNAzyme sequence.