Discovery,Development, and Patent Trends on Molnupiravir: A Prospective Oral Treatment for COVID-19

The COVID-19 pandemic needs no introduction at present. Only a few treatments are available for this disease, including remdesivir and favipiravir. Accordingly, the pharmaceutical industry is striving to develop new treatments for COVID-19. Molnupiravir, an orally active RdRp inhibitor, is in a phase 3 clinical trial against COVID-19. The objective of this review article is to enlighten the researchers working on COVID-19 about the discovery, recent developments, and patents related to molnupiravir. Molnupiravir was originally developed for the treatment of influenza at Emory University, USA. However, this drug has also demonstrated activity against a variety of viruses, including SARS-CoV-2. Now it is being jointly developed by Emory University, Ridgeback Biotherapeutics, and Merck to treat COVID-19. The published clinical data indicate a good safety profile, tolerability, and oral bioavailability of molnupiravir in humans. The patient-compliant oral dosage form of molnupiravir may hit the market in the first or second quarter of 2022. The patent data of molnupiravir revealed its granted compound patent and process-related patent applications. We also anticipate patent filing related to oral dosage forms, inhalers, and a combination of molnupiravir with marketed drugs like remdesivir, favipiravir, and baricitinib. The current pandemic demands a patient compliant, safe, tolerable, and orally effective COVID-19 treatment. The authors believe that molnupiravir meets these requirements and is a breakthrough COVID-19 treatment.     

Alloy formation at the Ni–Al interface for nickel films deposited on Al(110) surfaces

Alloy formation at the Ni–Al interface for thin nickel films deposited on Al(110) surfaces has been studied using high-energy ion scattering/channeling (HEIS) and X-ray photoelectron spectroscopy (XPS). For nickel atoms deposited at room temperature on Al(110), a large amount of nickel–aluminum intermixing occurs at the interface. For the first two monolayers (ML) of deposited nickel, an NiAl-like compound is formed. The intermixing continues with a different rate, forming an Ni₃Al-like compound for nickel coverages from 2 to 8 ML, at which point a nickel metal film begins to grow on the surface. Nickel atoms deposited at 250°C on the Al(110) surface exhibit no surface compound formation, but diffuse up to 400 Å into the aluminum substrate. Interatomic potentials based on the embedded-atom method (EAM) are used in a Monte Carlo approach to simulate the evolution of the Ni–Al(110) interface as a function of the nickel coverage. The calculated ion-scattering yields and X-ray photoelectron intensities from nickel and aluminum atoms in these simulated interfaces are in good quantitative agreement with the experimental results. The simulations show a high-density Ni–Al alloy forming at the Al(110) surface which apparently inhibits outward diffusion of aluminum, leading to the more nickel-rich alloy and finally nickel film growth. The ion-scattering simulations show an unusually large amount of backscattering occurring below the Ni–Al(110) interface, apparently associated with defocusing of the incident ion beam.     

Exploiting the Chiral Ligands of Bis(imidazolinyl)- and Bis(oxazolinyl)thiophenes—Synthesis and Application in Cu-Catalyzed Friedel–Crafts Asymmetric Alkylation

Five new C₂-symmetric chiral ligands of 2,5-bis(imidazolinyl)thiophene (L1–L3) and 2,5-bis(oxazolinyl)thiophene (L4 and L5) were synthesized from thiophene-2,5-dicarboxylic acid (1) with enantiopure amino alcohols (4a–c) in excellent optical purity and chemical yield. The utility of these new chiral ligands for Friedel–Crafts asymmetric alkylation was explored. Subsequently, the optimized tridentate ligand L5 and Cu(OTf)₂ catalyst (15 mol%) in toluene for 48 h promoted Friedel–Crafts asymmetric alkylation in moderate to good yields (up to 76%) and with good enantioselectivity (up to 81% ee). The bis(oxazolinyl)thiophene ligands were more potent than bis(imidazolinyl)thiophene analogues for the asymmetric induction of the Friedel–Crafts asymmetric alkylation.     

Characterization of structural modifications in poly-tetra-fluoroethylene induced by electron beam irradiation

The effects of electron beam irradiation doses on the poly-tetra-fluoroethylene (PTFE) have been studied. Several techniques, such as X-ray diffraction (XRD), differential scanning calorimetry (DSC), mechanical properties and Fourier transform infrared spectroscopy (FTIR) were applied to characterize the PTFE samples and to study the radiation effects on the crystal structure of the polymer.The irradiation dose up to 150 kGy showed an increase in the crystallinity degree of PTFE, which has been observed and confirmed during the DSC and XRD measurements. The increase in crystallinity was attributed to the scissions of the chain in the amorphous region. Moreover, the number-average molecular weights were estimated from the heat of crystallization measured by DSC technique. The results indicated that the molecular weights were decreased by increasing the heat of crystallization due to irradiation with doses up to 150 kGy. Radiation resistance of the irradiated and non-irradiated PTFE was investigated during its mechanical properties at room temperature. The dose at half value of the elongation at break is about 3.10 kGy while the dose at half value of the tensile strength is about 1.70 kGy.     

Photon statistics of non-stationary gaussian-markovian light

The photon counting distribution due to gaussian-markovian light relaxing from an excited state to equilibrium, is calculated and compared with the distribution due to stationary light having the same average intensity.     

Enhancing the axial resolution of quantum optical coherence tomography by chirped quasi-phase matching

We show theoretically that a chirped quasi-phase-matching nonlinear crystal structure can significantly enhance the axial resolution in quantum optical coherence tomography by increasing the spectral width of the generated entangled photon pairs. For pulsed pumps we show how the pump-pulse duration affects the maximum resolution attainable.     

The influence of Fe doping on the structural, magnetic and optical properties of nanocrystalline ZnO particles

We report the results of an investigation of Fe-doped nanocrystalline ZnO particles synthesized using the co-precipitation method with doping concentrations from 5 up to 31 at%. To understand how the dopant influenced the structural, magnetic and optical properties of nanocrystalline ZnO particles, X-ray diffraction, energy dispersive X-ray spectroscopy, infrared absorption spectroscopy, UV-vis spectroscopy, electron spin resonance spectroscopy (ESR) and vibrating sample magnetometer were employed. From the analysis of X-ray diffraction, our Fe-doped nanocrystalline ZnO particles are identified as having the wurtzite crystal structure and the unit cell volume increases with increasing doping concentrations. However, impurity phases are observed for Fe contents higher than 21 at%. Sample structures were further studied by infrared spectra, from which a broad and strong absorption band in the range of 400-700 cm⁻¹ and -OH stretching vibrational mode at approximately 3400 cm⁻¹ were observed. Ultraviolet-visible measurements showed a decrease in the energy gap with increasing Fe content, probably due to an increase in the lattice parameters. Magnetic measurements showed a ferromagnetic behavior for all samples. ESR results indicate the presence of Fe in both valence states Fe²⁺ and Fe³⁺.     

Bimetallic Iron–Palladium Catalyst System as a Lewis-Acid for the Synthesis of Novel Pharmacophores Based Indole Scaffold as Anticancer Agents

The Friedel–Crafts reaction between substituted indoles as nucleophiles with chalcones-based benzofuran and benzothiophene scaffolds was carried out by employing a highly efficient bimetallic iron–palladium catalyst system. This catalytic approach produced the desired bis-heteroaryl products with low catalyst loading, a simple procedure, and with acceptable yield. All synthesized indole scaffolds 3a–3s were initially evaluated for their cytotoxic effect against human fibroblast BJ cell lines and appeared to be non-cytotoxic. All non-cytotoxic compounds 3a–3s were then evaluated for their anticancer activities against cervical cancer HeLa, prostate cancer PC3, and breast cancer MCF-7 cell lines, in comparison to standard drug doxorubicin, with IC₅₀ values 1.9 ± 0.4 µM, 0.9 ± 0.14 µM and 0.79 ± 0.05 µM, respectively, and appeared to be moderate to weak anticancer agents. Fluoro-substituted chalcone moiety-containing compounds, 3b appeared to be the most active member of the series against cervical HeLa (IC₅₀ = 8.2 ± 0.2 µM) and breast MCF-7 cancer cell line (IC₅₀ = 12.3 ± 0.04 µM), whereas 6-fluroindol-4-bromophenyl chalcone-containing compound 3e (IC₅₀ = 7.8 ± 0.4 µM) appeared to be more active against PC3 prostate cancer cell line.     

MOFs for desulfurization of fuel oil: Recent advances and future insights

Nowadays, desulfurization of fuel oil has raised concern globally because of strict industrial and environmental legislations. Albeit hydrodesulfurization (HDS) has been extensively used in oil refineries to produce low sulfur oil (< 10 ppm) but not been proven as effective method for the removal of dibenzothiophene (DBT), benzothiophene (TH) and their derivatives. Subsequently, adsorptive desulfurization (ADS) and oxidative desulfurization (ODS) methods have been developed to achieve high removal efficiency. In the past decade, metal–organic frameworks (MOFs) and its composites as oxidative catalysts, as well as adsorbents, have attracted the researchers owing to high surface area, tunable properties, and reusable. The present review comprises use of MOFs and their composites for the removal of sulfur from fuel oil via ODS and ADS processes. Additionally, physicochemical properties of MOFs, mechanism, pros and cons of both process, regeneration, and future challenges have been discussed briefly. Moreover, current limitations and future prospective are also discussed.     

Evaluation of spectral dispersion of optical constants of a-Se films from their normal-incidence transmittance spectra using Swanepoel algebraic envelope approach

Spectral dispersions of index of refraction \({n(\lambda )}\) and extinction coefficient \({\kappa (\lambda )}\) of undoped amorphous selenium (a-Se) films of three thicknesses (d?≈?0.5, 0.75, and 1.0 µm) were evaluated by analyzing experimental room-temperature normal-incidence transmittance-wavelength (\({{T_{{\text{exp}}}}(\lambda )} - \lambda\)) data (λ =?400–1100 µm) of their air-supported {a-Se film/thick glass slide}-stacks using Swanepoel’s transmission envelope theory of uniform films. Above a wavelength \({{\lambda _c}\,\, \approx \,\,640\;{\text{nm}}}\), as-measured \({{T_{{\text{exp}}}}(\lambda )}\,\, - \,\lambda\) spectra display well-resolved maxima and minima, with minor shrinkage in transparent and weak absorption regions (750–1100 nm). Below \({\lambda _{\text{c}}}\), a smeared sharp decline of \({{T_{{\text{exp}}}}(\lambda )}\) with decreasing λ, signifying strong absorption in a-Se films and existence of band-tail localized states. For λ > λ _c, the \({n\,(\lambda )}\, - \,\lambda\) data retrieved from algebraic envelope procedures followed a Sellmeier-like dispersion relation, with the best-fit values of high-frequency dielectric constant \({{\varepsilon _\infty }\, \approx \,\,{\text{4.9}}}\), static index of refraction \({{n_{\text{0}}} = n\left( {E\, \to \,{\text{0}}} \right)\,\, \approx \,\,{\text{2.43}}}\), and resonance wavelength \({{\lambda _0}\, \approx \,490\,\,{\text{nm}}}\), which may be assigned to onset of photogeneration in a-Se. Urbach-like dependency of absorption coefficient \({\alpha (h{{\nu }})}\) of a-Se films on photon energy \({h{{\nu }}}\) was realized with an Urbach-tail breadth of 85 meV. All achieved optical parameters were found to be slightly dependent on film thickness. Findings of present algebraic analysis are consistent with reported literature results obtained on the basis of other optical analytical approaches.