Search Results (187)

Wooden waste railroad ties preserved with coal tar creosote oil represent a specific source of polluting substances. The aim of this study was to investigate and compare extraction capacity due to solvent extraction of fifteen frequently used organic solvents for the purpose of decontamination treatment of waste wooden railroad ties, while recovering wood for reuse. Pure organic solvents, ethanol 96%, propan-2-ol, deionized water, dichloromethane, acetone, n-hexane, mixture n-hexane/acetone (V/V = 1/1), cyclohexane, methanol, N,N-dimethyl formamide, toluene, ethyl acetate, acetonitrile, amyl acetate, medical gasoline, n-pentane and n-butyl acetate were for leaching pollutants from waste railroad ties. The highest extraction capacity was achieved using dichloromethane, where 7.50 to 7.89 wt.% of total sixteen polycyclic aromatic hydrocarbons were extracted from waste railroad tie chips. The most promising solvents for the treatment exhibited extraction efficiency which decreases in a series dichloromethane > n-hexane/acetone > acetone > methanol > ethanol 96% > propan-2-ol > cyclohexane > toluene > n-hexane. Solvent extraction represents a novel approach for treatment of wooden waste railroad ties. The experiments are based on the search for a management process for the treatment of wood waste railroad ties that is simple, low energy consumption, efficient and could potentially be applied for large scale. Full article

Chemical complexity is not a nuisance to be minimized in origin of life research, it is an enabling condition. This second edition of the Special Issue on the Origin of Life in Chemically Complex Messy Environments gathers contributions that embrace multicomponent mixtures, dynamic geochemical settings, and nonequilibrium processes. The papers collected here survey surface hydrothermal routes to reactive nitriles, groundwater evolution of alkaline lakes, and transition metal sulfide-driven amino acid and amide formation without cyanide. They report one pot nucleoside and nucleotide synthesis from formamide over cerium phosphate, review non aqueous organophosphorus pathways, and probe peptide rich mixtures and formose type networks under serpentinization associated minerals. The issue also advances conceptual frameworks, including atmospheric photochemical signatures for biosignature discrimination, the role of chiral mineral surfaces in enantioseparation, and computational simulations of the origin of LUCA. Together, these studies position messy chemistry as a crucible that turns chemical diversity and environmental heterogeneity into routes toward organization and function. Full article

Tecovirimat is an antiviral agent approved for the treatment of orthopoxvirus infections including smallpox, cowpox and monkeypox. A key challenge in its synthesis lies in the generation of maleimide intermediates, which traditionally requires high-temperature thermal rearrangement and often results in low-to-moderate yields. Classical methods rely on heating in toluene above 70 °C, limiting scalability and efficiency. Herein, we present a mild and efficient organocatalytic approach to the synthesis of tecovirimat intermediates, using a room-temperature Mumm rearrangement of isomaleimide precursors. The reaction is catalyzed by 10 mol% imidazole and N-hydroxysuccinimide. As a representative example for one of the tecovirimat synthesis methods, intermediate N-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-4-(trifluoromethyl)benzamide was synthesized from p-trifluoromethylbenzohydrazide at a 71% yield over two steps. Additionally, N-(2,5-dioxopyrrol-1-yl)(tert-butoxy)formamide was obtained from Boc-hydrazide at a 37% yield. The methodology was sufficiently extended to other benzohydrazide-derived isomaleimides. To support the mechanistic rationale, preliminary PM7 semiempirical computational studies were performed, highlighting the electronic features facilitating the transformation. This work offers a practical and scalable route to tecovirimat intermediates, overcoming key synthetic bottlenecks and enhancing the efficiency of antiviral drug production. Full article

Background/Objective: Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β plaques, derived from the amyloid precursor protein through sequential cleavage by β-secretase 1 (BACE-1) and γ-secretase. BACE-1 is therefore a key drug target for designing of selective inhibitors to avoid off-target effects associated with BACE-2 inhibition. The objective of this study was to design novel BACE-1 inhibitors using a structure-based drug design approach. Methods: A focused compound library was designed based on the SAR of N-(4-fluorophenyl)formamide derivatives. In silico ADME predictions were performed to assess pharmacokinetic suitability. Compounds showing favorable ADME profiles were subjected to molecular docking against the BACE-1 enzyme. The top-scoring hit, compound 9.7 (−5.48 (kcal/mol), was further evaluated using a 200 ns MD simulation to assess the stability of its binding interactions with BACE-1. Results: Designed compounds indicated acceptable physicochemical and ADME characteristics. Molecular docking identified compound 9.7 as exhibiting favorable binding interactions with binding pocket residues of BACE-1. The 200 ns MD simulation further confirmed the stability of the docked complex. MD simulations confirmed that 9.7 forms stable interactions with the catalytic residue ASP32 and key hydrophobic residues TRP115 and PHE108 of BACE-1. These important interactions are absent in the reference compound verubecestat. Conclusions: The multi-step computational analysis suggests that compound 9.7 is a promising and selective BACE-1 inhibitor. Its favorable ADME profile, favorable docking interactions, and stable MD simulation behavior highlight its potential as a hit compound for further optimization in the development of anti-Alzheimer’s agents. Full article

Fumarate, succinate, maleate, dihydroxyfumarate, D–tartarate, L–tartarate, DL–tartarate, L-malate, D-malate, oxaloacetate, citrate, and DL-isocitrate in the 5–100 μM concentration range were incubated in 12.5 mM HEPES/25 mM TRIS base containing 200 μM Eu³⁺–tetracycline and 60% (v/v) formamide (pH unadjusted). After 30 min of incubation, they were separated at 4 °C by capillary electrophoresis utilizing laser-induced luminescence detection with 12.5 mM HEPES/25 mM TRIS base containing 60% formamide as the running buffer. All analytes yielded peaks, with the exception of fumarate, succinate, and maleate. L-Malate was detected down to 100 nM. The main component of this study was the analysis of malate. The objective was to develop a stereoselective methodology for the detection of L-malate. This was achieved by varying the formamide concentration and separation temperature. When the temperature was increased to 22 °C and the formamide concentration decreased to 40%, the sensitivity for L-malate was diminished about 10-fold, but that for D-malate was eliminated. This combination of conditions allowed for the stereospecific analysis of L-malate. Full article

Kappa opioid receptor (KOR) antagonists may have therapeutic potential to prevent stress-induced relapse in abstinent individuals with cocaine use disorder (CUD). The macrocyclic peptide [D-Trp]CJ-15,208 (cyclo[Phe-D-Pro-Phe-D-Trp]) is an orally bioavailable, brain–penetrant selective KOR antagonist that prevents stress-induced reinstatement of cocaine-seeking behavior in a mouse model of CUD. We synthesized and evaluated analogs of this lead compound with substitutions for the D-Trp residue to identify analogs that exhibit more potent central KOR antagonism following oral administration. The peptides were synthesized by a combination of solid phase and solution peptide synthetic methodologies, and their pharmacological activity was evaluated both in vitro (for KOR affinity, selectivity and antagonism) and in vivo (for antinociception and KOR antagonism), with promising analogs evaluated for their ability to prevent stress-induced reinstatement of cocaine-seeking behavior in the mouse conditioned place preference (CPP) assay. A variety of substituted D-Phe or modified D-Trp derivatives were tolerated by KOR with retention of significant KOR antagonism in vivo after oral administration. Macrocyclic peptide pretreatment, per os, significantly prevented stress-induced reinstatement of cocaine CPP at doses of 10 and 30 mg/kg of [D-Phe⁴]CJ-15,208, 4, and 30 mg/kg of [D-Trp(formamide)]CJ-15,208, 3, which are 6-fold and 2-fold lower, respectively, than that needed for {D-Trp]CJ-15,208. Full article

Understanding how redox-active ligands coordinate to metal centers of different oxidation states is essential for applications ranging from metal remediation and recycling to drug discovery. In this study, coordination complexes of nickel(II), copper(II), and zinc(II) chloride salts were synthesized by mixing the salts with either arylazoformamide (AAF) or arylazothioformamide (ATF) ligands in toluene or methanol. The AAF and ATF ligands coordinate through their 1,3-heterodienes, N=N–C=O and N=N–C=S, respectively, and, due to their known strong binding, the piperidine and pyrrolidine formamide units were selected, as was the electron-donating methoxy group on the aryl ring. A total of 12 complexes were obtained, representing potential chelation events from ligand-driven oxidation of zerovalent metals and/or coordination of oxidized metal salts. The X-ray crystallography revealed a range of coordination patterns. Notably, the Cu(II)Cl₂ complexes, in the presence of ATF, produce [ATF-CuCl]₂ dimers, supporting a potential reduction event at the copper, while other metals with ATF and all metals with AAF remain in the 2+ oxidation state. Hirshfeld analysis was performed on all complexes, and it was found that most interactions across the complexes were dominated by H…H, followed by Cl…H/H…Cl, with metals showing very little to no interaction with other atoms. Spectroscopic techniques such as UV–VIS absorption, NMR (when diamagnetic), and FTIR, in addition to electrochemical studies support the metal–ligand coordination. Full article

As a continuation of our research on the synthesis and study of biological properties of new derivatives of 3-aminopyridin-2(1H)-ones, we investigated the Leuckart–Wallach and Eschweiler–Clarke reactions with selected 3-aminopyridin-2(1H)-ones and 3-(arylmethyl)pyridin-2(1H)-ones. It was found that under the conditions of the Leuckart–Wallach reaction with aromatic aldehydes in formic acid, mainly formamides of the indicated 3-aminopyridones are formed. The Eschweiler–Clarke reaction of 3-aminopyridin-2(1H)-ones and 3-(arylmethyl)pyridin-2(1H)-ones with an aqueous solution of formaldehyde result in the formation of tertiary N–benzyl(methyl)amino)-pyridin-2(1H)-ones in almost quantitative yield. The 3-aminopyridin-2(1H)-ones derivatives synthesized by us were used for the biological screening of cytoprotective activity in the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test to determine the viability of fibroblast cells isolated from the NIH/Swiss mouse embryo (NIH/3T3, Gibco). It was found that many of the studied compounds under the conditions of our experiment exhibited significant cytoprotective effects, thereby enhancing cell survival. Full article

Aiming at the problems of complex process flow, high energy consumption, and difficult emulsification in the preparation of traditional SBS-modified emulsified asphalt, a preparation method of fast-melting SBS (referred to as SBS-T) modified emulsified asphalt based on the integration of modification and emulsification is proposed. Based on surface free energy theory, the contact angles between three rapid-melting SBS-modified emulsified asphalts with different dosages and three probe liquids (deionized water, glycerol, and formamide) were measured using the sessile drop method. The adhesion performance of the asphalt–aggregate system was studied by means of micromechanical methods. The evaluation indicators such as the cohesion work of the emulsified asphalt, the adhesion work of asphalt–aggregate, the spalling work, and the energy ratio were analyzed. The results show that the SBS-T modifier can significantly improve the thermodynamic properties of emulsified asphalt. With increasing modifier content, the SBS-T-modified emulsified asphalt demonstrated enhanced cohesive work, improved asphalt–aggregate adhesive work, and increased energy ratio, while showing reduced stripping work. At equivalent dosage levels, the SBS-T-modified emulsified asphalt demonstrates a slight improvement in adhesion performance to aggregates compared to conventional SBS-modified emulsified asphalt. The SBS-T emulsified modified asphalt provides an effective technical solution for the preventive maintenance of asphalt pavements. Full article

A reliable synthetic method based on the already known Blanc–Quelet methodology has been developed for upgrading bio-based phenols into valuable electrophilic mono-, di-, and trifunctional benzyl chlorides. These compounds show significant potential as building blocks for polymer production and the synthesis of specialty chemicals. As an example of their applicability, their direct interaction with formamide has been evaluated, obtaining an effective transformation towards the corresponding N-formylamides. These compounds represent versatile synthetic precursors to a variety of functionalized targets. Full article

In surface energy tests of asphalt materials, the inaccuracy of the calculation method (e.g., least squares (LS)) and the arbitrary selection of chemical reagent combinations lead to unstable results, threatening the quantitative evaluation of asphalt–aggregate adhesion durability. This study addresses these two scientific deficiencies with the following findings: (1) when simultaneous equations are used to calculate the asphalt surface energy parameters, the total least squares method should be used instead of the classical least squares method to reduce the fitting error; (2) the selection of the reagent combination should be based on which one is the most rational in terms of the physical characterization, leap degree, abnormal values, and other requirements, and the reagent combination with the fewest abnormal values should be chosen as the best scheme. The results show that (1) compared with the classical least squares method, the total least squares method reduces the fitting error between the calculated and real values of asphalt surface energy parameters and improves the accuracy and stability of the calculation results; (2) the best reagent combination scheme is WFSD (distilled water + formamide + dimethyl sulfoxide + diiodomethane). The calculated values of asphalt surface energy parameters were more accurate and reasonable, and the calculation results had no abnormal values. Compared with WFEG (distilled water + formamide + ethylene glycol + glycerol), the error rate of the reagent combination scheme WFSD in calculating the total surface energy of two kinds of asphalt was reduced by 17.71% and 64.80%, respectively. These findings establish a reliable framework for the accurate quantification of surface energy, addressing the critical issue of reagent-dependent variability in the results and strengthening the scientific basis for evaluating the durability of asphalt pavement. Full article

Microbiological quality control in cosmetic and pharmaceutical products is crucial for consumer safety. Traditional culture-based detection methods, such as plating on selective media, are time-consuming and may lack sensitivity. Fluorescence In Situ Hybridisation (FISH), a molecular and culture-independent technique, enables rapid and precise microbial identification by targeting specific RNA or DNA sequences with fluorescent probes. In this study, a novel DNA-FISH probe was developed for the detection of Candida albicans in cosmetic formulations. The probe’s specificity was assessed in silico and experimentally using flow cytometry (flow-FISH) on C. albicans and non-target microorganisms, including Pichia kudriavzevii, commonly known as Candida krusei, Saccharomyces cerevisiae, Wickerhamomyces anomalus, Escherichia coli, and Staphylococcus aureus. The probe exhibited 98.9% hybridization efficiency with C. albicans, yielding a fluorescence intensity (FI) of 25,000 (a.u.), while non-target yeasts demonstrated minimal hybridization (4.7%, 2.3%, and 1.9% for C. krusei, S. cerevisiae, and W. anomalus, respectively) and bacteria showed negligible FI. Additionally, the probe’s applicability was evaluated in a tonic formulation, where C. albicans’ hybridization efficiency was slightly reduced to 88.4%, suggesting that formulation components may influence probe performance. Nevertheless, the probe maintained high specificity and efficiency without formamide, a toxic reagent commonly used in FISH. These findings highlight the potential of FISH probes for rapid, accurate, and safe microbial detection, offering a valuable tool for microbiological quality control in the cosmetics industry. Full article

The influence of sodium 4-vinylbenzenesulfonate on the electrooxidation of phenols and naphthols was studied in dimethylformamide (DMF). The usually observed deactivation of phenol in non-aqueous environments was suppressed upon addition of sodium 4-vinylbenzenesulfonate, and signals of all studied compounds were highlighted due to the diminished background current. As in other cases, the latter is attributable to the solvent. The 4-vinylbenzenesulfonate salt underwent electroinitiated polymerization close to the electrode surface excluding all other compounds from it within the timescale of the measurements. The polymeric products were partially removed by dissolution; therefore, improved signal reproducibilities could be reached. The investigation was extended to pulsed voltammetric techniques widely used in analytical chemistry (differential pulse, normal pulse, square wave voltammetry). Among these techniques, differential pulse voltammetry showed the best performance. Therefore, during its use, the analytical usefulness of adding the unsaturated additive in optimal concentration was estimated in the case of some phenols and naphthols. Successful calibration for picric acid was attained in DMF. Full article

Tegoprazan is a potassium ion-competitive acid blocker (P-CAB) and a novel inhibitor of gastric acid secretion. The compound exists in two crystalline polymorphs, A and B, whose structures had not previously been reported. In this study, both polymorphs were analyzed by liquid- and solid-state NMR, revealing identical tautomeric states. Using this information, the crystal structures were determined from laboratory powder X-ray diffraction data by simulated annealing and Rietveld refinement. Both forms were found to crystallize in the monoclinic space group P2₁, with Z = 4 and two independent molecules in the asymmetric unit (Z′ = 2). To assess the stability and reliability of the refined structures, we attempted geometry optimization and vibrational analysis using DFT-D methods. However, due to the high conformational complexity of Z′ = 2 systems, these calculations failed to converge or produced imaginary frequencies. Instead, single-point energy calculations were performed on the refined models. The resulting relative energy differences, together with solubility data, van’t Hoff enthalpies, and DSC profiles, consistently indicated that Polymorph A is more stable than Polymorph B. These results highlight the challenges of structure validation via DFT-D for complex molecular crystals and demonstrate the value of integrating experimental and computational approaches for polymorph characterization. Full article

In this work, three methods for the synthesis of composites based on poly(ortho-toluidine) (POT) and WS₂ are reported: (a) the solid-state interaction (SSI) of POT with WS₂ nanoparticles (NPs); (b) the in situ chemical polymerization (ICP) of ortho-toluidine (OT); and (c) the electrochemical polymerization (ECP) of OT. The preparation of WS₂ sheets was performed by the ball milling of the WS₂ NPs followed by ultrasonication in the solvent N,N’-dimethyl formamide. During the synthesis of the POT/WS₂ composites by SSI and ICP, an additional exfoliation of the WS₂ NPs was reported. In this work, we demonstrated the following: (a) the ICP method leads to POT/WS₂ composites, which contain repeating units of POT in the leucoemeraldine salt (LS) state, while (b) the ECP method leads to POT/WS₂ composites, which contain repeating units of POT in the emeraldine salt (ES) state. Capacitances equal to 123.5, 465.76, and 751.6 mF cm⁻² in the cases of POT-ES/WS₂ composites, synthesized by SSI, ICP, and ECP, respectively, were reported. Full article