Monthly Archives: March 2024

Manipulating sensitivities of planar oxadiazole‐based high performing energetic materials

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Manipulating sensitivities of planar oxadiazole-based high performing energetic materials

The results from this study demonstrate that the planarity in azoles does contribute toward insensitivity. The safety advantage of planar 1,3,4-oxadiazole-tetrazole mixed azole is combined with the energy of nitroamine to achieve better physiochemical properties.


Abstract

Nitrogen-rich energetic materials based on five-membered azoles, such as tetrazoles, triazoles, oxadiazoles, pyrazoles, and imidazoles, have garnered significant attention in recent years due to their environmental compatibility while maintaining high performance. These materials, including explosives, propellants, and pyrotechnics, are designed to release energy rapidly and efficiently while minimizing the release of toxic or hazardous byproducts and have attracted potential applications in the defense and space industries. The presence of extensive NC, NN, and NN high energy bonds in azoles provides high enthalpies of formation and facilitates intermolecular interactions through π-stacking which may help with reducing sensitivity to external stimuli. Now, we report on the synthesis and energetic properties of N-(5-(1H-tetrazol-5-yl)-1,3,4-oxadiazol-2-yl)nitramide (5) and its energetic salts. These new high nitrogen–oxygen-containing materials have attractive feature applications of insensitivity and increased performance.

Synthesis and antiviral activity of novel imidazo[2,1‐b]thiazoles coupled with morpholine and thiomorpholines

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Synthesis and antiviral activity of novel imidazo[2,1-b]thiazoles coupled with morpholine and thiomorpholines

Synthesis and screening of morpholine and thiomorpholine coupled imidazo[2,1-b]thiazoles for their in vitro antiviral activity against influenza virus, resulted two analogs, 7d and 7e as most potent analogs with favorable toxicity profile.


Abstract

Herein described the synthesis and antiviral evaluation of a novel series of morpholine and thio-morpholine coupled imidazo[2,1-b]thiazoles. The three-step reaction sequence involving the condensation of 1,3-dichloroacetone with thiourea followed by coupling with morpholine and thiomorpholine and finally cyclization with substituted α-bromoacetophenones yielded the desired imidazothiazoles 7(a–l). Screening of all the new compounds for their in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells, resulted in two potent analogs, 7d (IC50: 1.1 μM, C50: >300 μM, SI = 273) and 7e (IC50: 2.0 μM, C50: >300 μM, SI = 150), with a favorable toxicity profile and are the best anti-influenza hit analogs for further structural optimization.

Synthesis, antiproliferative activity, 3D‐QSAR, and molecular docking studies of novel L‐carvone‐derived pyrimidine‐urea compounds

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Synthesis, antiproliferative activity, 3D-QSAR, and molecular docking studies of novel L-carvone-derived pyrimidine-urea compounds

A novel series of L-carvone-derived pyrimidine-urea compounds with antiproliferative activity were designed and synthesized, along with the investigation for their structure-activity relationship.


Abstract

To explore novel natural product-based nitrogen-containing heterocyclic compounds with antiproliferative activity, 20 L-carvone-derived pyrimidine-urea compounds 4a–4t were synthesized through the multi-step reaction of L-carvone, and structurally characterized by Fourier transform infrared (FT-IR), hydrogen-1 nuclear magnetic resonance (1H-NMR), Carbon-13 nuclear magnetic resonance (13C-NMR), and High-resolution mass spectrometry (HRMS). Besides, the in vitro antiproliferative activity of the target compounds against HepG2, Hela, and MCF-7 cells was evaluated by methyl thiazolyl tetrazolium (MTT) assay. According to the results, the target compounds showed certain inhibitory activities against the tested cancer cell lines, and five compounds (4b, 4h, 4k, 4l, and 4t) exhibited better inhibition activities against Hela cells than the positive control (5-FU). Among them, compound 4b held significant antiproliferative activities against Hela and HepG2 cells, and thus deserved further study as a leading compound of new anticancer drugs. In addition, an effective and reasonable three-dimensional quantitative structure-activity relationships (3D-QSAR) model was built by the Comparative molecular field analysis (CoMFA) method to analyze the relationship between the structures of the target compounds and their antiproliferative activities (expressed as pIC50) against Hela cells, and proven to have good predictive ability. Molecular docking was carried out to study the possible binding modes of compound 4b and Survivin, and it was found that compound 4b could be well embedded into the active site, along with the formation of several hydrogen bonds and hydrophobic interactions.

Novel pyrazole‐biphenyl‐carboxamides for SARS‐CoV2 entry‐level restriction and microbial infections

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Novel pyrazole-biphenyl-carboxamides for SARS-CoV2 entry-level restriction and microbial infections

Novel pyrazole-biphenyl carboxamides showed dual antimicrobial and SARS-CoV2 entry-level inhibition activity potentials. The antimicrobial activity was broad-spectrum and the in-silico SARS-CoV2 spike protein, a main causative agent of COVID-19, was found to restrict its entry-level interaction with human Angiotensin Converting Enzyme (hACE). Thus, these novel molecules could have been the future drugs to treat both microbial and viral infections.


Abstract

Microbial diseases including viral infection are big issues globally. Effective medicinal discovery for them is the need for the day. In this study, we report pyrazole-biphenyl-carboxamides (4a-l) validated for their SARS-CoV2 entry-level restriction effect over studying the protein–protein interaction of SARS-CoV2 with human ACE protein. Their extended antimicrobial properties were also evaluated. Online and offline software tools predicted MD simulation and ADMET druggability in silico. The antimicrobial efficacy of all compounds was also evaluated against Gram+ve Streptococcus pneumoniae (MTCC 1936), Staphylococcus aureus (MTCC 737) and Gram-ve Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 424) (bacteria). In the results, compounds 4g and 4i were evenly active against both bacteria at a low concentration range (MIC: 1.00 to 9.5 μg/mL) and displayed lesser toxicity to tested mammalian cells (EC100 = 75 μg/mL). Furthermore, it was able to kill metabolically inactive bacterial cells and eradicate established biofilms of Methicillin-resistant Staphylococcus aureus (MRSA). Both the compounds inhibited DNA gyrase well with an IC50 0.25 μM (96% relative activity) and 0.52 μM (97% relative activity) respectively. Compounds (4a-l) showed restrictive efficiency of SARS-CoV2 spike protein (SC2SP) and human angiotensin-converting enzyme 2 (hACE2) entry-level association in COVID-19 in silico. To assess this ability, firstly, we identified the crucial amino acid residues involved in the interface of SARS-CoV-2 and hACE2 virtually. We recognized the ability of 4a-l binding to the binding interface to SARS-CoV2; thus, the interaction of SC2SP-hACE2 was effectively inhibited.

Uranium Chemistry in liquid Ammonia: Compounds obtained by adventitious Presence of Moisture or Air

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Uranium Chemistry in liquid Ammonia: Compounds obtained by adventitious Presence of Moisture or Air

We present the syntheses and crystal structures of several adventitious hydrolysis products of UCl4, UBr4, UBr5, and UO2Cl2. We obtained compounds containing dinuclear μ-O-bridged uranium(IV) cations, mixed-valent uranyl(V)-uranyl(VI) tetra- and octanuclear complex cations, and also a compound where the isoelectronic species UO2 2+ and UN2 formed a complex.


Abstract

UCl4, UBr4, UBr5, or UO2Cl2 reacted with excess liquid ammonia – in adventitious presence of moisture and/or air – and formed some peculiar uranium compounds of which we present the crystal structures. [(NH3)7(N3)U(μ-O)U(NH3)8]Cl5 ⋅ 7NH3 contains a dinuclear μ-O-bridged uranium(IV) cation, [{(NH3)4UO2}2(μ-O)]Cl2 ⋅ 4NH3 features a dinuclear μ-O-bridged uranyl(VI) cation, while the compounds [(U(VI)O2)2(U(V)O2)2(μ3-O)2(NH3)12]Br2 ⋅ 6NH3 and [(U(VI)O2)4(U(V)O2)4(μ3-O)4(NH3)22]Br4 ⋅ 16NH3 are mixed-valent containing uranyl(V)-uranyl(VI) units. For these tetra- and octanuclear complex cations we observed that the O atoms of the uranyl(V) units can be μ2- and even μ3-bridging to uranyl(VI) units, while the O atoms of the latter are acting as terminal ligands only. [(NH3)8U(μ-N)U(NH3)5(μ-N)UO2(NH3)4]Br6 ⋅ 18NH3 presents the first example of a compound where the isoelectronic species UO2 2+ and UN2 formed a complex with the NUN unit bridging to the U atom of the uranyl(VI) cation. As it is can be difficult to distinguish between N and O atoms with X-ray diffraction, quantum-chemical calculations at the DFT-PBE0/TZVP level of theory were carried out which unequivocally confirmed the atom assignments in the crystal structures. The chemical bonding in the complex cations was studied using intrinsic bonding orbitals and allowed for an additional discrimination of the U(V) and U(VI) atoms in the mixed-valent compounds.