Dichloromethane Research Articles

An eco-friendly and cost-effective HPTLC method for quantification of COVID-19 antiviral drug and co-administered medications in spiked human plasma

The coronavirus-2 has led to a global pandemic of COVID-19 with an outbreak of severe acute respiratory syndrome leading to worldwide quarantine measures and a rise in death rates. The objective of this study is to propose a green, sensitive, and selective densitometric method to simultaneously quantify remdesivir (REM) in the presence of the co-administered drug linezolid (LNZ) and rivaroxaban (RIV) in spiked human plasma. TLC silica gel aluminum plates 60 F254 were used as the stationary phase, and the mobile phase was composed of dichloromethane (DCM): acetone (8.5:1.5, v/v) with densitometric detection at 254 nm. Well-resolved peaks have been observed with retardation factors (Rf) of 0.23, 0.53, and 0.72 for REM, LNZ, and RIV, respectively. A validation study was conducted according to ICH Q2 (R1) Guidelines. The method was rectilinear over the concentration ranges of 0.2–5.5 μg/band, 0.2–4.5 μg/band and 0.1–3.0 μg/band for REM, LNZ and RIV, respectively. The sensitivities of REM, LIN, and RIV were outstanding, with quantitation limits of 128.8, 50.5, and 55.8 ng/band, respectively. The approach has shown outstanding recoveries ranging from 98.3 to 101.2% when applied to pharmaceutical formulations and spiked human plasma. The method’s greenness was assessed using Analytical Eco-scale, GAPI, and AGREE metrics.

Mapping the Influence of Solvent Composition over the Characteristics of Polylactic Acid Nanofibers Fabricated by Electrospinning

AbstractThis study investigated the solubility of poly(lactic acid) (PLA) in various solvents (to achieve an 8 % (w/v) polymer solution) and its impact on the morphology of electrospun PLA nanofibers. Several solvents, such as dichloromethane (DCM), chloroform (CHL), tetrahydrofuran (THF), acetone (AC), acetonitrile (ACTNR), dimethylformamide (DMF), dimethylacetamide (DMAc), ethylene glycol (ETGLY), distilled water (WATER), methanol (MEOH), formic acid (FA), and n‐hexane (NHX) were used in their pure and binary forms at several ratios (4 : 1, 2 : 1, 1 : 1, 1 : 2, 1 : 3, and 1 : 4). The study aims to explore the correlation between PLA solubility and its electrospinnability using solvents mapped from the Teas graph across different parameter zones and chemical groups. Hansen solubility parameters, including dispersion cohesion fractional solubility parameter (fd), the polar cohesion fractional solubility parameter (fp) was employed to identify the most effective solvents for PLA dissolution. Teas graph analysis highlighted a correlation between PLA solubility and solvent proximity to Hansen solubility parameters. Additionally, the solubility time varied between 1 hour and 24 hours. Polar solvents such as DCM, CHL, THF, ACTNR, and FA were able to dissolve 8 % (w/v) of PLA at different times, but only very high and effective dissolution of PLA was achieved in pure DCM and CHL whereas FA dissolved PLA in 24 hours, which resulted in the slowest solubility rate. Several structures of nanofibers, such as smooth, heterogenous, porous, fibrous, and beaded, were observed and discussed accordingly in terms of solvent type and ratio. The average nanofiber diameter ranged between 0.18 μm and 3.81 μm. Moreover, physical tests, including surface tension, density, viscosity, and conductivity, were conducted on solvent systems and CHL displayed higher viscosity, while ACTNR had the lowest viscosity and highest conductivity among pure solvents. According to the results of our study, it is possible to design further studies with the aim of deciding which solvents or binary forms should be applied to dissolve PLA within a certain time. The desired structure can be easily arranged to be used as a filter, biomimicking tissue environment, drug delivery system, or extra.

Multi-Step Synthesis, Characterization and Bioevaluation of Novel 2-(3-Methoxy-9H-carbazol-9-yl)-N-phenyl Acetamide Analogues

In this work, the multi-step synthesis and characterization of novel 2-(3-methoxy-9H-carbazol-9-yl)-N-phenyl acetamide analogues is presented. These analogues were synthesized from 2-(3-methoxy-9H-carbzol-9-yl)acetyl chloride with substituted aromatic primary amines in the presence of organic base such as triethylamine and methylene dichloride under reflux conditions. The elemental analysis and structures of these novel compounds were elucidated by analyzing spectral data obtained through 1H NMR, 13C NMR and LCMS techniques. The bioevaluation of these newly synthesized compounds has been studied by evaluating their antibacterial and antifungal activities against various kinds of bacterial and fungal strains, respectively.

Impact of Hazardous Chemical Compounds on the Reproductive System Reported in Sanitary Products

Abstract: A particular group of routine essentials, feminine hygiene items, might expose women to plasticizers and antimicrobial agents. The entire world produces and uses a vast amount of chemicals, some of which may be harmful to reproductive health. The majority of chemicals and work environments have not been investigated for their potential to harm reproductive systems up to this point. The Republic of Korea and other recently industrialized nations have accumulated chemicals and other toxicants quickly, endangering well-being, especially their reproductive systems. (UTC) Women frequently utilize feminine hygiene products (FHPs) as personal care products. ( 2 )According to a broad review, sanitary pads have an impact on endometriosis, vaginal microflora, and vulvar or vaginal skin. Female health has also been found to be impacted by social contexts, such as the use of hygiene products or puberty education. (temp) Chemicals that are dangerous now or in the future are included in the category of sanitary products. Infertility, ovarian cancer, skin rashes, and skin darkening are just a few of the problems that can arise from using sanitary products that contain hazardous chemicals and harm the reproductive system. menstrual cycle imbalance. Sanitary products contain a variety of substances, including VOC, furans, phthalates, bisphenols, and dioxin. Jppd Diapers and sanitary pads are composed of synthetic plastic materials, which may leak when being used. In the present study, the quantities of phthalates (DBP, DEHP, DEP, and BBP) and volatile organic compounds (VOCs) (methylene chloride, toluene, and xylene) in sanitary pads and diapers were measured.

Preparation of Fe(II) − 6-chloro-3-hydroxy-7-methyl-2-(2′-thienyl)-4-oxo-4H-1-benzopyran complex for analytical, biological & computational studies

An easy, rapid, sensitive and selective spectrophotometric method which shows maximum absorbance at 433 nm to detect micro amount of Fe(II) with 6-chloro-3-hydroxy-7-methyl-2-(2′-thienyl)-4-oxo-4H benzopyran(CHMTB) has been developed which form a stable dark brownish complex in an acidic environment which is extractable in dichloromethane (DCM). The complex showed molar absorptivity coefficient and sandell’ssensitivity 2.335 x 104 l mol-1and 0.0023 µg cm−2 respectively.The correlation value and detection limit for this method is 0.9998 and 0.0893 µg ml−1 respectively. Various cations and anions/complexing agents had no effect on the detection of divalent iron.The DFT/B3LYP/6-31G(d,p) method is a commonly used computational approach used for studying molecular properties and to calculate energy gaps for complex and ligand which are foundto be 0.0767 eV and 0.1380 eV respectively. Global reactivity descriptors provide valuable information about the reactivity and stability of molecules. Molecular Electrostatic Potential (MEP) analysis is a useful tool for identifying potential sites for nucleophilic or electrophilic attacks on chemical structures. The complex interaction with anti-cancer, antibacterial, and antifungal agents had been thoroughly studied along with the selectivity of the method by its detection in presense of other metal ions.

AIEE-active dichlorobenzene and chlorobenzene ratiometric fluorescent probe based on [2.2]paracyclophane

Two AIEE-active [2.2]paracyclophanyl-based diester and monoester (1a and 1b) were facilely synthesized by one-pot method and applied as ratiometric fluorescent probe to detect dichlorobenzene (DCB) and chlorobenzene (CB). Compared with compound 1b, 1a exhibits high sensitivity and low detection limits for DCB and CB in dichloromethane (DCM), particularly, the detection sensitivities for ortho-dichlorobenzene (o-DCB), meta-dichlorobenzene (m-DCB) and chlorobenzene can be modulated by AIEE behavior with lower detection limits of 23.64, 56.27, and 5.92 ppm, respectively in THF/H2O mixed solutions with water fraction (fw) of 70 % due to the formation of aggregation-state. The X-ray structure analysis, theoretical calculations and photophysical properties in different solvents were investigated to reveal the distinctive photophysical behaviors of 1a and 1b. The facile synthesis, X-ray structure, AIEE modulated sensing properties for o-DCB, m-DCB, and CB in DCM and THF/H2O mixed solutions make 1a potential application as fluorescent probe for trace DCB and CB detection in drinking water.

Catalytic oxidation of dichloromethane over W-Nb composite oxide catalysts modified by Co: The influence of redox ability and acidity

Catalytic oxidation of highly toxic chlorinated volatile organic compounds often places high demands on the anti-poisoning ability of the catalysts. Here, Co/WNb catalysts with different Co loadings were prepared for the catalytic oxidation of dichloromethane (DCM). Notably, the interaction between the active components and the carriers resulted in a high Co2+/Co3+ ratio on the catalyst surface, which facilitated the generation of oxygen vacancies (Ov) and enhanced the redox properties of the catalyst. Furthermore, the WNb carrier offered ample surface acidic sites, bolstering the catalyst's resilience against chlorine poisoning. The study revealed that achieving a more balanced combination of redox properties and acidity was beneficial for enhancing the catalytic degradation efficiency of DCM. 3% Co/WNb exhibited the best catalytic activity (T90 = 269 °C). The catalyst also exhibited excellent stability and outstanding water resistance. Potential reaction routes for the catalytic oxidation of DCM were explored using in-situ IR spectra analysis. This study offers novel insights for the development of efficient, stable, and environmentally friendly catalysts for DCM degradation.

Phytochemical Constituents of Sap, Root and Leaf Extracts of Calotropis Procera from Select Regions in the Gambia

Medicinal plants serve as potential cure for animal and human diseases as they contain phytochemicals for therapeutic values. Most of the modern drugs produced are isolated from herbal plants. This research reports on the phytochemical constituents of the methanolic and dichloromethane (DCM) extracts of the sap, root and leaf of Calotropis procera in three select regions in The Gambia namely the West Coast Region, North Bank Region, and Lower River Region. The sap was collected in an air-tight test tube; the root and leaf were dried at room temperature for three weeks and one month, respectively and further ground into powder. Soxhlet extraction of the sap was done using both DCM for 30 minutes at 40oC to 50oC and methanol for 3 h at 60oC to 70oC. The root and leaf were extracted using cold maceration for 72 h. The methanolic extracts showed the presence of alkaloids, quinones, saponins, flavonoids, terpenoids, steroids, and carbohydrates in the sap and leaf. Quinones were present in the DCM extract of the sap and root, but absent in the leaf. While flavonoids and terpenoids were present in the sap and leaf extracts, they were absent in the root. Alkaloids, saponins, and steroids were absent in the sap and root extracts, but found in the leaf. Tannins and phenols were absent in both the methanolic and DCM extracts. The results of each of the samples collected at the three different regions were similar in their phytochemical constituents for the extracting solvents; but varied with the different solvent. The findings of this research allude to the fact that the sap, root and leaf of C. procera are good sources of therapeutic compounds that are responsible for the use of this plant in herbal medicine in The Gambia.

LC-MS/MS profiling of Tipuana tipu flower, HPLC-DAD quantification of its bioactive components, and interrelationships with antioxidant, and anti-inflammatory activity: in vitro and in silico approaches

BackgroundFabaceae plays a crucial role in African traditional medicine as a source of large number of important folk medication, agriculture and food plants. In a search of potential antioxidant and anti-inflammatory candidates derived from locally cultivated plants, the flowers of Tipuana tipu (Benth.) Lillo growing in Egypt were subjected to extensive biological and phytochemical studies. The impact of the extraction technique on the estimated biological activities was investigated.MethodsThe flowers were extracted using different solvents (aqueous, methanol, water/methanol (1:1), methanol/methylene chloride (1:1), and methylene chloride). The different extracts were subjected to antioxidant (DPPH, ABTS, and FRAP) and anti-inflammatory (COX-2 and 5-LOX) assays. The methanol extract was assessed for its inhibitory activity against iNOS, NO production, and pro-inflammatory cytokines (NF-KB, TNF-R2, TNF-α, IL-1β, and IL-6) in LPS-activated RAW 264.7 macrophages. The composition-activity relationship of the active methanol extract was further investigated using a comprehensive LC–QTOF-MS/MS analysis. The major identified phenolic compounds were further quantified using HPLC-DAD technique. The affinity of representative compounds to iNOS, COX-2, and 5-LOX target active sites was investigated using molecular docking and molecular dynamics simulations.ResultsThe methanol extract exhibited the highest radical scavenging capacity and enzyme inhibitory activities against COX-2 and 5-LOX enzymes with IC50 values of 10.6 ± 0.4 and 14.4 ± 1.0 µg/mL, respectively. It also inhibited iNOS enzyme activity, suppressed NO production, and decreased the secretion of pro-inflammatory cytokines. In total, 62 compounds were identified in the extract including flavonoids, coumarins, organic, phenolic, and fatty acids. Among them 18 phenolic compounds were quantified by HPLC-DAD. The highest docking scores were achieved by kaempferol-3-glucoside and orientin. Additionally, molecular dynamics simulations supported the docking findings.ConclusionThe flower could be considered a potentially valuable component in herbal medicines owing to its unique composition and promising bioactivities. These findings encourage increased propagation of T. tipu or even tissue culturing of its flowers for bioprospecting of novel anti-inflammatory drugs. Such applications could be adopted as future approaches that benefit the biomedical field.

Implementation of bridged copolymerisation to optimise the optical properties of porphyrin: applications in dye-sensitized solar cells

This study explores the concept of all-organic sensitisation of dye-sensitized solar cells (DSSCs) by using a cosensitization approach to model efficient porphyrin-based photosensitizers. The aim is to enhance the absorption defects and light response current of porphyrin dyes, which have been reported in the literature. In this work, eight (8) natural porphyrin derivatives obtained through bridged copolymerisation of free base porphyrin and tetraazaporphyrin have been modelized and analysed. Their geometric parameters, stability energies, chemical stabilities, and photochemical properties were studied using density functional theory (DFT) methods in both gaseous and dichloromethane (DCM) phases. The analysis of photochemical properties, including maximum absorption wavelength ( λ max ), light harvesting efficiency (LHE), electron injection driving force ( Δ G inj ), regeneration driving force ( Δ G reg ), and excited state lifetime ( τ ) of the studied photosensitizers, show significant improvement compared to the parent dye (free base porphyrin) and some recent derivatives SM315 and YD2-o-C8. It is worth noting that the eight ( 8 ) modelled dyes from porphyrin show broader LHE curves not only compared to the parent dye, but also compared to the SM315 dye, which may lead to a higher running photo density. This study highlights the effectiveness of bridged copolymerisation for developing high-performance DSSCS based on porphyrin.

Environmental assessment of an innovative adhesive for the footwear industry: road map for product development

Abstract Purpose This work presents an environmental assessment of two adhesives to evaluate the replacement of the traditional adhesive (PU) used in the footwear industry by a novel adhesive based on a microencapsulation approach (PUMC) which is more favorable from the safety and technical perspectives. The PU adhesive is polyurethane-based, while the PUMC adhesive is polyurethane-based but with its isocyanate compounds microencapsulated, increasing storage life and reducing risks related to the exposure of workers with the adhesives. Methods The potential environmental impact of the adhesives was evaluated using the life cycle assessment (LCA) methodology. A detailed process model was developed (both for laboratory and for a pilot-scale implementation) to investigate the environmental impacts associated with these processes. The functional unit was one kilogram of adhesive (PU and PUMC adhesives) produced. A cradle-to-customers’ gate approach was defined. The system boundary starts from extraction of resources, through material production, until adhesive use. This includes microcapsule production in the case of the PUMC adhesive. This study investigates the important drivers behind the environmental impacts to help guide commercialization efforts. A scenarios study/sensitivity analysis was conducted to determine the response of the PUMC adhesive system to the variability of the model, scenarios, and parameters. Results The results show that the PU adhesive environmental impact is due to acetone and polyol consumption in the production stage. In the PUMC adhesive system, acetone consumption and microcapsule production are the major factors responsible for the environmental impact. Polybutylene adipate terephthalate (PBAT), dichloromethane (DCM), and isophorone diisocyanate (IPDI) consumption are the major factors responsible for the environmental impact of the microcapsules’ production. A sensitivity analysis was conducted using three alternative scenarios focused on the reduction in material consumption and increase in material recuperation, as well as using an alternative renewable energy source. Although the traditional PU adhesive has a lower impact, it was found that the three alternative PUMC adhesive systems can become comparable to the traditional PU adhesive. Conclusions This study shows the advance and development of a new technology for microencapsulation of isocyanate in adhesives and its environmental advantages and disadvantages with respect to a traditional product that uses non-encapsulated isocyanate. Finally, it was shown that there is significant potential for minimizing some environmental impacts of the PUMC adhesive, such as optimizing the microcapsules’ production stage, increasing the production efficiency to decrease the required material consumption.

Cellulose Nitrates-Blended Composites from Bacterial and Plant-Based Celluloses.

Cellulose nitrates (CNs)-blended composites based on celluloses of bacterial origin (bacterial cellulose (BC)) and plant origin (oat-hull cellulose (OHC)) were synthesized in this study for the first time. Novel CNs-blended composites made of bacterial and plant-based celluloses with different BC-to-OHC mass ratios of 70/30, 50/50, and 30/70 were developed and fully characterized, and two methods were employed to nitrate the initial BC and OHC, and the three cellulose blends: the first method involved the use of sulfuric-nitric mixed acids (MAs), while the second method utilized concentrated nitric acid in the presence of methylene chloride (NA + MC). The CNs obtained using these two nitration methods were found to differ between each other, most notably, in viscosity: the samples nitrated with NA + MC had an extremely high viscosity of 927 mPa·s through to the formation of an immobile transparent acetonogel. Irrespective of the nitration method, the CN from BC (CN BC) was found to exhibit a higher nitrogen content than the CN from OHC (CN OHC), 12.20-12.32% vs. 11.58-11.60%, respectively. For the starting BC itself, all the cellulose blends of the starting celluloses and their CNs were detected using the SEM technique to have a reticulate fiber nanostructure. The cellulose samples and their CNs were detected using the IR spectroscopy to have basic functional groups. TGA/DTA analyses of the starting cellulose samples and the CNs therefrom demonstrated that the synthesized CN samples were of high purity and had high specific heats of decomposition at 6.14-7.13 kJ/g, corroborating their energy density. The CN BC is an excellent component with in-demand energetic performance; in particular, it has a higher nitrogen content while having a stable nanostructure. The CN BC was discovered to have a positive impact on the stability, structure, and energetic characteristics of the composites. The presence of CN OHC can make CNs-blended composites cheaper. These new CNs-blended composites made of bacterial and plant celluloses are much-needed in advanced, high-performance energetic materials.

Chitin nanocrystals-stabilized emulsion as template for fabricating injectable suspension containing polylactide hollow microspheres

One of the promising applications of rod-like chitin nanocrystals (ChNCs) is the use as particle emulsifier to develop Pickering emulsions. We reported a ChNC-stabilized oil-in-water emulsion system, and developed a Pickering emulsion-templated method to prepare polylactide (PLA) hollow microspheres here. The results showed that both non-modified ChNCs and acetylated ChNCs could well emulsify the dichloromethane (DCM) solution of PLA-in-aqueous mannitol solution systems, forming very stable emulsions. At the same oil-to-water ratios and ChNC loadings, the emulsion stability was improved with increasing acetylation levels of ChNCs, accompanied by reduced size of droplets. Through the solvent evaporation, the PLA hollow microspheres were templated successfully, and the surface structure was also strongly dependent on the acetylation level of ChNCs. At a low level of acetylation, the single-hole or multi-hole surface structure formed, which was attributed to the out-diffusion of DCM caused by the solvent extraction and evaporation. These surface defects decreased with increased acetylation levels of ChNCs. Moreover, the aqueous suspension with as-obtained PLA microspheres revealed shear-thinning property and good biocompatibility, thereby had promising application as injectable fillers. This work can provide useful information around tuning surface structures of the Pickering emulsion-templated polymer hollow microspheres by regulating acetylation level of ChNCs.

Drosophila melanogaster as a model organism for diabetes II treatment by the ethyl acetate fraction of Atriplex halimus L.

Type 2 diabetes (T2D) is the most common metabolic disorder. The undesirable effects of synthetic drugs demand a search for safe antidiabetic agents. This study aimed to assess the antidiabetic activity of different fractions of Atriplex halimus (petroleum ether 60-80, methylene chloride, ethyl acetate, and n-butanol) using Drosophila melanogaster larvae. Titers of total glucose and trehalose, as well as larval weight, were measured and compared with those of control and diabetic larvae. The expression of Drosophila insulin-like peptides (DILP2 and DILP3) and adipokinetic hormone (AKH) was evaluated. The results revealed a significant increase in total glucose, trehalose, and a decrease in body weight in the larvae fed a high-sugar diet compared with those in the control. When larvae fed diets containing the tested fractions, the total glucose and trehalose decreased to the control level, and the body weight increased. DILP2, DILP3, and AKH exhibited significant decreases upon treatment with A. halimus ethyl acetate. Metabolomic profiling of the ethyl acetate fraction of A. halimus revealed the presence of flavonoids and flavonoid glycosides. After docking screening to predict the most powerful moiety, we discovered that flavonoid glycosides (especially eriodictyol-7-O-neohesperidoside) have a greater affinity for the pocket than the other moieties. The results indicated the therapeutic activity of the A. halimus ethyl acetate fraction against induced T2D in Drosophila larvae. The antidiabetic activity may be attributed to flavonoids, which are the main components of the A. halimus ethyl acetate fraction.

Supercritical fluid extraction of ginger herbal dust bioactives with an estimation of pharmacological potential using in silico and in vitro analysis

Extensive filter tea production in the last decade has increased the amount of generated waste. Due to the particle size (less than 0.315 mm), this material, also known as herbal dust, cannot be packed into the filter tea bags. According to previous studies, valuable bioactive compounds have been recovered from herbal dusts. Therefore, this study is focused on the valorization of ginger (Zingiber officinale) herbal dust, which is commonly used for the treatment of digestive disorders, colds, and various health issues. To obtain highly valuable extracts rich in non-polar and low-polar bioactive compounds novel Supercritical carbon dioxide (SFE-CO2) extraction was applied. As a reference technique, Soxhlet extraction (methylene chloride) was employed. The chemical profiles of all extracts were determined by GC-MS. The most dominant compounds, according to the results, were hydrocarbon sesquiterpene zingiberene (7.51%–14.28%), sesquiterpenes β-sesquiphellandrene (3.70%–7.34%), β-bisabolene (3.54%–6.93%), ar-curcumene (3.02%–6.19%) and non-volatile phenolic compounds 6-gingerol (25.33%–31.11%), 6- shogaol (12.21%–14.91%). Based on the chemical profile of the extracts, the in silico study was carried out where the effects of ginger compounds with a focus on diabetes were specified. Besides, the most potential SFE-CO2 extract was selected for the investigation of effects on short- and long-term cell viability on liver cancer cells.

Kinetic Modulation of Carbon Nanotube Growth in Direct Spinning for High-Strength Carbon Nanotube Fibers.

With impressive individual properties, carbon nanotubes (CNTs) show great potential in constructing high-performance fibers. However, the tensile strength of as-prepared carbon nanotube fibers (CNTFs) by floating catalyst chemical vapor deposition (FCCVD) is plagued by the weak intertube interaction between the essential CNTs. Here, we developed a chlorine (Cl)/water (H2O)-assisted length furtherance FCCVD (CALF-FCCVD) method to modulate the intertube interaction of CNTs and enhance the mechanical strength of macroscopic fibers. The CNTs acquired by the CALF-FCCVD method show an improvement of 731% in length compared to that by the conventional iron-based FCCVD system. Moreover, CNTFs prepared by CALF-FCCVD spinning exhibit a high tensile strength of 5.27 ± 0.27 GPa (4.62 ± 0.24 N/tex) and reach up to 5.61 GPa (4.92 N/tex), which outperforms most previously reported results. Experimental measurements and density functional theory calculations show that Cl and H2O play a crucial role in the furtherance of CNT growth. Cl released from the decomposition of methylene dichloride greatly accelerates the growth of the CNTs; H2O can remove amorphous carbon on the floating catalysts to extend their lifetime, which further modulates the growth kinetics and improves the purity of the as-prepared fibers. Our design of the CALF-FCCVD platform offers a powerful way to tune CNT growth kinetics in direct spinning toward high-strength CNTFs.

Solvent Replacement Strategies for Processing Pharmaceuticals and Bio-Related Compounds—A Review

An overview of solvent replacement strategies shows that there is great progress in green chemistry for replacing hazardous di-polar aprotic solvents, such as N,N-dimethylformamide (DMF), 1-methyl-2-pyrrolidinone (NMP), and 1,4-dioxane (DI), used in processing active industrial ingredients (APIs). In synthetic chemistry, alcohols, carbonates, ethers, eucalyptol, glycols, furans, ketones, cycloalkanones, lactones, pyrrolidinone or solvent mixtures, 2-methyl tetrahydrofuran in methanol, HCl in cyclopentyl methyl ether, or trifluoroacetic acid in propylene carbonate or surfactant water (no organic solvents) are suggested replacement solvents. For the replacement of dichloromethane (DCM) used in chromatography, ethyl acetate ethanol or 2-propanol in heptanes, with or without acetic acid or ammonium hydroxide additives, are suggested, along with methanol acetic acid in ethyl acetate or methyl tert-butyl ether, ethyl acetate in ethanol in cyclohexane, CO2-ethyl acetate, CO2-methanol, CO2-acetone, and CO2-isopropanol. Supercritical CO2 (scCO2) can be used to replace many organic solvents used in processing materials from natural sources. Vegetable, drupe, legume, and seed oils used as co-extractants (mixed with substrate before extraction) can be used to replace the typical organic co-solvents (ethanol, acetone) used in scCO2 extraction. Mixed solvents consisting of a hydrogen bond donor (HBD) solvent and a hydrogen bond acceptor (HBA) are not addressed in GSK or CHEM21 solvent replacement guides. Published data for 100 water-soluble and water-insoluble APIs in mono-solvents show polarity ranges appropriate for the processing of APIs with mixed solvents. When water is used, possible HBA candidate solvents are acetone, acetic acid, acetonitrile, ethanol, methanol, 2-methyl tetrahydrofuran, 2,2,5,5-tetramethyloxolane, dimethylisosorbide, Cyrene, Cygnet 0.0, or diformylxylose. When alcohol is used, possible HBA candidates are cyclopentanone, esters, lactone, eucalytol, MeSesamol, or diformylxylose. HBA—HBA mixed solvents, such as Cyrene—Cygnet 0.0, could provide interesting new combinations. Solubility parameters, Reichardt polarity, Kamlet—Taft parameters, and linear solvation energy relationships provide practical ways for identifying mixed solvents applicable to API systems.

Molecular networking-based mass spectral identification of Brucea javanica (L.) Merr. metabolites and their selective binding affinities for dengue virus enzymes

Brucea javanica, a valued traditional medicinal plant in Malaysia, known for its fever-treating properties yet remains underexplored for its potential antiviral properties against dengue. This study aims to simultaneously identify chemical classes and metabolites within B. javanica using molecular networking (MN), by Global Natural Product Social (GNPS), and SIRIUS in silico annotation. Liquid chromatography-mass spectrometry (LC-MS2)-based MN explores chemical diversity across four plant parts (leaves, roots, fruits, and stem bark), revealing diverse metabolites such as tryptophan-derived alkaloids, terpenoids, and octadecadenoids. Simultaneous LC-MS2 and MN analyses reveal a discriminative capacity for individual plant components, with roots accumulating tryptophan alkaloids, fruits concentrating quassinoids, leaves containing fusidanes, and stem bark primarily characterised by simple indoles. Subsequently, extracts were evaluated for dengue antiviral activity using adenosine triphosphate (ATP) and plaque assays, indicates potent efficacy in the dichloromethane (DCM) extract from roots (EC50 = 0.3 μg/mL, SI = 10). Molecular docking analysis of two major compounds; canthin-6-one (264) and 1-hydroxy-11-methoxycanthin-6-one (275) showed potential binding interactions with active sites of NS5 RNA-dependent RNA polymerase (RdRp) of dengue virus (DENV) protein. Subsequent in vitro evaluation revealed compounds 264 and 275 had a promising dengue antiviral activity with SI value of 63 and 1.85. These identified metabolites emerge as potential candidates for further evaluation in dengue antiviral activities.

Disentangling the formation, mechanism, and evolvement of the covalent methanesulfonyl fluoride acetylcholinesterase adduct: Insights into an aged-like inactive complex susceptible to reactivation by a combination of nucleophiles.

Chemical warfare nerve agents and pesticides, known as organophosphorus compounds inactivate cholinesterases (ChEs) by phosphorylating the serine hydroxyl group located at the active site of ChEs. Over the course of time, phosphorylation is followed by loss of an organophosphate-leaving group and the bond with ChEs becomes irreversible, a process known as aging. Differently, structurally related irreversible catalytic poisons bearing sulfur instead of phosphorus convert ChEs in its aged form only by covalently binding to the key catalytic serine. Kinetic and crystallographic studies of the interaction between Torpedo californica acetylcholinesterase (TcAChE) and a small organosulfonate, methanesulfonyl fluoride (MSF), indeed revealed irreversibly methylsulfonylated serine 200, to be isosteric with the bound aged sarin/soman analogues. The potent bulky reversible inhibitor 7-bis-tacrine (BTA) adopts, in the active site of the crystal structure of the MSF-enzyme adduct, a location and an orientation that closely resemble the one being found in the crystal structure of the BTA-enzyme complex. Remarkably, the presence of BTA accelerates the rate of methanesulfonylation by a factor of two. This unexpected result can be explained on the basis of two facts: i) the steric hindrance exerted by BTA to MSF in accessing the active site and ii) the acceleration of the MSF-enzyme adduct formation as a consequence of the lowering of the rotational and translational degrees of freedom in the proximity of the catalytic serine. It is well known that pralidoxime (2-Pyridine Aldoxime Methyl chloride, 2-PAM) alone or in the presence of the substrate acetylcholine cannot reactivate the active site serine of the TcAChE-MSF adduct. We show that the simultaneous presence of 2-PAM and the additional neutral oxime, 2-[(hydroxyimino)methyl]-l-methylimidazol (2-HAM), triggers the reactivation process of TcAChE within the hour timescale. Overall, our results pave the way toward the likely use of a cocktail of distinctive oximes as a promising recipe for an effective and fast reactivation of aged cholinesterases.

Sucrose esters of aryldihydronaphthalene-type lignans, and antitumor activity of extracts of Moltkiopsis ciliata (Forssk.) aerial parts

One new compound (3f-[(7′R,8′R)-4,4′-dihydroxy-5-methoxy-2,7′-cycloligna-7-en-9-methoxycarbonyl, 9′-carbonyl-O-] -β- D-fructofuranosyl- (2→1)-α- D-glucopyranoside) (Moltkiopsin A) (2) was isolated and identified from the extract of aerial parts of the wild Egyptian plant Moltkiopsis ciliata (Frossk.), family Boraginaceae, for the first time, along with two aryldihydronaphthalene lignans 3f→9′:6f→9-[(7′R,8′R)-4,4′- dihydroxy-3,3′,5-trimethoxy-2,7′-cycloligna-7-en-9,9′-dicarbonyl]-6g-acetyl-α-D-gluco pyranosyl-(1→2) -β-D-fructofuranoside (Trigonotin A) (1) which was reported for the first time from this plant species and a known compound 3f→9′:6f→9-[(7′R,8′R)-4,4′- dihydroxy-3,3′,5-trimethoxy-2,7′-cycloligna-7-en-9,9′-dicarbonyl]-α-D-gluco pyranosyl - (1→2)- β-D- fructofuranoside (Trigonotin C) (3). These compounds were separated and purified using different chromatographic techniques and their structures were elucidated by extensive 1D (1H and 13C NMR), and 2D NMR (COSY, HSQC, and HMBC), besides ESI-MS spectral methods. Extracts were screened as antioxidant, antitumor and antibacterial. The different extracts showed moderate to strong antioxidant capacities in DPPH assays. Ethyl acetate, methylene chloride and crude methanol extracts exhibited the most significant free radicals scavenging activity when compared to the standard antioxidant vitamin C. Hexane and butanol fractions showed the highest cytotoxicity against the cancer cell lines HepG2 and MCF-7.