Despite being largely absent from natural products and biological processes, fluorine plays a conspicuous and increasingly important role within pharmaceuticals and agrochemicals, as well as in materials science.1a−1c Indeed, as many as 35% of agrochemicals and 20% of pharmaceuticals on the market contain fluorine.1d Fluorine is the most electronegative element in the periodic table, and the introduction of one or more fluorine atoms into a molecule can result in greatly perturbed properties. Fluorine substituents can potentially impact a number of variables, such as the acidity or basicity of neighboring groups, dipole moment, and properties such as lipophilicity, metabolic stability, and bioavailability. The multitude of effects that can arise from the introduction of fluorine in small molecules in the context of medicinal chemistry has been extensively discussed elsewhere.2 For these reasons, methods to introduce fluorine into small organic molecules have been actively investigated for many years by specialists in the field of fluorine chemistry. However, particularly in the past decade, a combination of the increasing importance of fluorine-containing molecules and the successful development of bench stable, commercially available fluorine sources has brought the expansion of fluorine chemistry into the mainstream organic synthesis community. This has resulted in an acceleration in the development of new fluorination methods and consequently in methods for the asymmetric introduction of fluorine.3 Catalytic asymmetric fluorination methods have inevitably lagged somewhat behind their nonasymmetric counterparts as understanding of the modes of reactivity of new fluorinating reagents must generally be developed and understood before they can be extended to enantioselective catalysis.3b Indeed, the last special issue of Chemical Reviews dedicated to fluorine chemistry, in 1996, contained no articles addressing asymmetric fluorine chemistry, and the editor of the issue noted that “although fluorine chemistry is much less abstruse now than when I entered the field a generation ago, it remains a specialized topic and most chemists are unfamiliar, or at least uncomfortable, with the synthesis and behavior of organofluorine compounds.”4 The field has undoubtedly undergone great change within the last two decades. As with the incorporation of the fluorine atom, the introduction of the trifluoromethyl (CF3) group into organic molecules can substantially alter their properties. As with fluorine, the prevalence of CF3 groups in pharmaceuticals and agrochemicals coupled with the development of new trifluoromethylating reagents also has led to a recent surge in the development of asymmetric trifluoromethylation and perfluoroalkylation. Although the fluorine and trifluoromethyl moieties are often found on the aromatic rings of many pharmaceutical and agrochemicals rather than in aliphatic regions, this may be a result of the lack of efficient methods for the asymmetric introduction of C–F and C–CF3 bonds into molecules; it could be the case that lack of chemical methods is restricting useful exploration of such molecules. However, there are still encouraging examples of drug candidates containing chiral fluorine and trifluoromethyl-bearing carbons (Figure (Figure11). Figure 1 Molecules of medicinal interest bearing C–F and C–CF3 stereocenters.
This paper briefly reviews the current status of the most popular methods for combined quantum mechanical/molecular mechanical (QM/MM) calculations, including their advantages and disadvantages. There is a special emphasis on very general link-atom methods and various ways to treat the charge near the boundary. Mechanical and electric embedding are contrasted. We consider methods applicable to gas-phase organic chemistry, liquid-phase organic and organometallic chemistry, biochemistry, and solid-state chemistry. Then we review some recent tests of QM/MM methods and summarize what we learn about QM/MM from these studies. We also discuss some available software. Finally, we present a few comments about future directions of research in this exciting area, where we focus on more intimate blends of QM with MM.
ObjectivesRetinal pigment epithelium (RPE) cell transplantation holds therapeutic promise for retinal degenerative diseases, but longitudinal monitoring of graft survival and efficacy remains clinically challenging. The aim of this study is to develop a simple and effective method for the therapeutic quantification of RPE cell transplantation and immune rejection in vivo.MethodsA nanoprobe was developed and modified to label donor RPE cells, and used to monitor the position and intensity of the fluorescence signal in vivo. Immunofluorescence staining and single-cell RNA sequencing (scRNA-seq) were used to characterize the cell types showing the fluorescence signal of the nanoprobe and to determine the composition of the immune microenvironment associated with subretinal transplantation.ResultsThe spatial distribution of the fluorescence signal of the nanoprobe corresponded with the site of transplantation, but the signal intensity decreased over time, while the signal distribution extended to the choroid. Additionally, the nanoprobe fluorescence signal was detected in the liver and spleen during long-term monitoring. Conversely, in mice administered the immunosuppressive drug cyclosporine A, the decrease in signal intensity was slower and the expansion of the signal distribution was less pronounced. Immunofluorescence analysis revealed a significant temporal increase in the proportion of macrophages with nanoprobe-labeled cells following transplantation. The stability and cell-penetrating ability of the nanoprobe enables the labeling of immune cell niches in RPE transplantation. Additionally, scRNA-seq analysis of nanoprobe-labeled cells identified MDK and ANXA1 signaling pathway in donor RPE cells as initiators of the immune rejection cascade, which were further amplified by macrophage-mediated pro-inflammatory signaling.ConclusionNear-infrared fluorescent nanoprobes represent a reliable method for in vivo tracing of donor RPE cells and long-term observation of nanoprobe distribution can be used to evaluate the degree of immune rejection. Molecular analysis of nanoprobe-labeled cells facilitates the characterization of the dynamic immune cell rejection niche and the landscape of donor-host interactions in RPE transplantation.
Mutairu O. Ajiboye, Ayodele A. Daniyan, Paul C. Okonkwo
et al.
Abstract This study presents the first investigation of halogen-substituted aniline-derived Schiff bases (SB1, SB2, SB3) as corrosion inhibitors for mild steel in Nigerian tar sand environments. Key novelty includes introducing inhibition power as a new gravimetric-based performance metric for alkaline conditions where electrochemical methods are limited. Tar sand from Ilubirin was processed with 0.58 M NaOH at 90 °C for 24 h with inhibitors at concentrations of 25–150 ppm. Gravimetric analysis, SEM–EDS, and Langmuir isotherm modelling revealed a significant corrosion rate with effectiveness order SB3 > SB2 > SB1. SB3 achieved 94.4% inhibition efficiency at 150 ppm due to a favourable molecular structure promoting enhanced adsorption. Langmuir analysis confirmed chemisorption (ΔG°ads > − 20 kJ mol−1), while microstructural evaluation demonstrated excellent surface protection. This research demonstrates the effectiveness of inhibition power in assessing corrosion inhibitors using gravimetric data due to the limitations of electrochemical measurement in tar sand environments. The study concludes that Schiff-based compounds offer promising solutions for corrosion control in a harsh alkaline tar sand processing environment.
Chemical technology, Physical and theoretical chemistry
High-energy electrons induce sample damage and motion at the nanoscale to fundamentally limit the determination of molecular structures by electron diffraction. Using a fast event-based electron counting (EBEC) detector, we characterize beam-induced, dynamic, molecular crystal lattice reorientations (BIRs). These changes are sufficiently large to bring reciprocal lattice points entirely in or out of intersection with the sphere of reflection, occur as early events in the decay of diffracted signal due to radiolytic damage, and coincide with beam-induced migrations of crystal bend contours within the same fluence regime and at the same illuminated location on a crystal. These effects are observed in crystals of biotin, a series of amino acid metal chelates, and a six-residue peptide, suggesting that incident electrons inevitably warp molecular lattices. The precise orientation changes experienced by a given microcrystal are unpredictable but are measurable by indexing individual diffraction patterns during beam-induced decay. Reorientations can often tilt a crystal lattice several degrees away from its initial position before irradiation, and for an especially beam-sensitive Zn(II)-methionine chelate, are associated with dramatic crystal quakes prior to 1 e− Å−2 electron beam fluence accumulates. Since BIR coincides with the early stages of beam-induced damage, it echoes the beam-induced motion observed in single-particle cryoEM. As with motion correction for cryoEM imaging experiments, accounting for BIR-induced errors during data processing could improve the accuracy of MicroED data.
Fabrizia Cilento, Barbara Palmieri, Giovangiuseppe Giusto
et al.
In the aerospace sector, structural and non-structural composite components are usually subjected to a wide range of environmental conditions. Among all, moisture can seriously damage these materials’ performance, reducing their mechanical, thermal, electrical, and physical properties as well as their service time. Lightweight protective barrier coatings capable of reducing the diffusion of gases and/or liquids in a material can improve the material’s resistance in humid environments. In this work, nanolamellar nanocomposites characterized by a high in-plane orientation of nanoplatelets have been employed as protective coatings for Kevlar sandwich panels, reproducing the construction of a nacelle engine. The effectiveness of the protection against water uptake of nanocomposites reinforced with graphite nanoplatelets (GNPs) at high filler contents (70, 80 and 90 wt%) has been investigated using moisture uptake and Ground-Air-Ground (GAG) tests in an environmental chamber. GNP coatings effectively work as barrier by generating highly tortuous paths for molecule diffusion. Results showed a dependence of the absorption on the coating composition and inner structure. Films @70 wt% GNPs showed the best protection against moisture uptake by delaying the phenomenon and reducing the absorption by −80% after 3 days and −35% after 41 days.
Aicha Bensouici, Nacera Baali, Roumaissa Bouloudenine
et al.
The aim of this work is the reduction and decoration of graphene oxide (GO) with magnesium oxide (MgO). In this work, GO was synthesized using modified Hummers’ protocol with (1:2), (1:3) and (1:4) graphite:potassium permanganate mass ratios. Subsequently, all GO samples (GO1:2, GO1:3, GO1:4) were reduced and decorated with magnesium oxide nanoparticles using a reflux technique at 100 °C for 2 h. Sample characterization using X-ray diffraction (XRD) reveals the presence of peaks relative to two different magnesium (Mg) phases: magnesium oxide (MgO) and magnesium hydroxide (Mg(OH)<sub>2</sub>). The presence of these spectral features, although characterized by a remarkable broadening, confirms the successful synthesis of Mg(OH)<sub>2</sub>-rGO-MgO nanocomposites. X-ray photoelectron spectroscopy (XPS) spectra indicate the presence of peaks assigned to C, O and Mg. The analysis of the high-resolution XPS spectra of these elements confirms once again the presence of Mg(OH)<sub>2</sub>-rGO-MgO compounds. The low temperature synthesis of Mg(OH)<sub>2</sub>-rGO-MgO nanocomposite exhibiting superior catalytic properties compared to MgO–rGO nanoparticles is an important step forward with respect to the current state of the art. The antioxidant activity of six nanocomposites, namely GO1:2, GO1:3, GO1:4, MgO–rGO1:2, MgO–rGO1:3 and MgO–rGO1:4, was determined using standard protocols based on a DPPH radicals scavenging assay, an H<sub>2</sub>O<sub>2</sub> scavenging assay, and a phosphomolybdate assay. All our samples exhibited dose-dependent antioxidant activity. Interestingly, among the different synthesized nanoparticles, GO1:4 and MgO–rGO1:4 showed the best performances.
Seyedhosein Payandeh, Florian Strauss, Andrey Mazilkin
et al.
The research and development of advanced nanocoatings for high-capacity cathode materials is currently a hot topic in the field of solid-state batteries (SSBs). Protective surface coatings prevent direct contact between the cathode material and solid electrolyte, thereby inhibiting detrimental interfacial decomposition reactions. This is particularly important when using lithium thiophosphate superionic solid electrolytes, as these materials exhibit a narrow electrochemical stability window, and therefore, are prone to degradation during battery operation. Herein we show that the cycling performance of LiNbO3-coated Ni-rich LiNixCoyMnzO2 cathode materials is strongly dependent on the sample history and (coating) synthesis conditions. We demonstrate that post-treatment in a pure oxygen atmosphere at 350 ℃ results in the formation of a surface layer with a unique microstructure, consisting of LiNbO3 nanoparticles distributed in a carbonate matrix. If tested at 45 ℃ and C/5 rate in pellet-stack SSB full cells with Li4Ti5O12 and Li6PS5Cl as anode material and solid electrolyte, respectively, around 80% of the initial specific discharge capacity is retained after 200 cycles (~ 160 mAh·g−1, ~ 1.7 mAh·cm−2). Our results highlight the importance of tailoring the coating chemistry to the electrode material(s) for practical SSB applications.
Identifying organic matter in laminae is fundamental to petroleum geology; however, many factors restrict manual quantification. Therefore, computer recognition is an appropriate method for accurately identifying microscopic components. In this study, we used support vector machine (SVM) to classify the preprocessed photomicrographs into seven categories: pyrite, amorphous organic matter, mineral matter, alginite, sporinite, vitrinite, and inertinite. Then, we performed a statistical analysis of the classification results and highlighted spatial aggregation of some categories using the kernel density estimation method. The results showed that the SVM can satisfactorily identify the macerals and minerals of the laminae, and its overall accuracy, kappa, precision, recall, and F1 are 82.86%, 0.80, 85.15%, 82.86%, and 82.75%, respectively. Statistical analyses revealed that pyrite was abundantly distributed in bright laminae; vitrinite and sporinite were abundantly distributed in dark laminae; and alginite and inertinite were equally distributed. Finally, the kernel density maps showed that all classification results, except inertinite, were characterized by aggregated distributions: pyrite with the distribution of multi-core centers, alginite, and sporinite with dotted distribution, and vitrinite with stripe distribution, respectively. This study may provide a new method to quantify the organic matter in laminae.
The use of fire safety engineering and performance-based techniques continues to grow in prominence as building design becomes more ambitious, increasing complexity. National fire safety enforcement agencies are tasked with evaluating and approving the resulting fire strategies, which have similarly continued to become more advanced and specialist. To assist with the evaluation of fire strategies, this paper introduces a methodology dedicated to sustainable building fire safety level simulations. The methodology derives from ideas originally introduced in British Standard Specification PAS 911 in 2007 and combines a visual representation of fire strategies with a semi-quantitative approach to allow for their evaluation. The concept can be applied to a range of industrial fire safety assessments and can be modified for specific needs relative to different industries.