Search Results (265)

Lolium rigidum is among the most prevalent and noxious weeds in cereal and perennial cropping systems worldwide and has developed resistance to several herbicide modes of action. This study employed a sensor-based smart farming method for the early screening of herbicide resistance across three L. rigidum accessions in Greece, followed by dose–response experiments with clodinafop-propargyl, glyphosate, and mesosulfuron-methyl + iodosulfuron-methyl. In the preliminary screening, herbicides were applied at their highest recommended rates, whereas the dose–response experiments included five application rates (0, 1/4X, X, 2X, and 4X). The EM2 accession exhibited confirmed resistance to mesosulfuron-methyl + iodosulfuron-methyl, with a resistance index of 5.31 and a five-fold increase in the herbicide rate required compared to the susceptible EM1 accession. For clodinafop-propargyl, the GR50 value of the resistant EM3 accession (147.97 g a.i. ha⁻¹) was approximately 2.5-fold higher than that of the susceptible EM2 accession (60.28 g a.i. ha⁻¹). Glyphosate application provided only partial biomass reduction in resistant accessions, indicating reduced susceptibility. In parallel, TaqMan assays were developed and validated to detect target-site mutations linked to resistance against EPSPS-, ACCase-, and ALS-inhibiting herbicides, supporting the molecular interpretation of the observed resistance patterns. Overall, the results demonstrate that sensor-based smart farming approaches can provide a rapid and reliable tool for the early screening of herbicide resistance, enabling more informed crop protection strategies and supporting sustainable weed management. Further research across diverse soil types and climatic conditions is warranted to validate and extend the applicability of these approaches. Full article

Coumarins represent a distinctive class of non-classical carbonic anhydrase inhibitors that interact with the entrance region of the catalytic pocket rather than directly coordinating the catalytic Zn²⁺ ion. In this study, a series of glycosylated coumarins was synthesized through a copper-catalyzed multicomponent reaction involving propargyl glycosides, salicylaldehyde, and tosyl azide, providing efficient access to iminocoumarin-based glycosides derived from natural carbohydrates. The inhibitory activity of the synthesized compounds was evaluated against human carbonic anhydrase isoforms I, II, IX, and XII using a stopped-flow CO₂ hydrase assay. The compounds showed negligible inhibition of the cytosolic isoforms hCA I and hCA II, while displaying moderate activity toward the tumor-associated isoforms hCA IX and hCA XII, with Ki values ranging from 12.9 to 41.8 μM. Among the series, 6-O-(2H-chromene-2-one-3-yl-methyl)-D-galactopyranose (10a) emerged as the most potent inhibitor of hCA IX and XII. Structure–activity relationship analysis indicated that deprotected glycosyl derivatives exhibit improved inhibitory activity compared to protected analogues. To rationalize these observations, molecular docking followed by molecular dynamics simulations and MM-GBSA binding free energy calculations were performed for both anomeric forms of compound 10a. The computational results revealed a clear preference for the β-anomer, particularly in hCA IX and XII, where favorable interactions with catalytic threonine residues and isoform-specific aromatic residues stabilize the ligand within the active-site entrance. These findings provide a molecular explanation for the experimentally observed selectivity and highlight glycosyl coumarins as potential starting points for further optimization toward selective inhibitors of tumor-associated carbonic anhydrases. Full article

The crosslinked binders formed by using glycidyl azide polymer (GAP) as the binder matrix and bis-propargyl succinate (BPS) as the curing agent have good application prospects in the field of solid propellants. Aiming at the shortcomings of traditional experimental research, such as high cost, and molecular dynamics (MD) simulation, which are time-consuming for complex combination problems, this study will realize accurate prediction of the mechanical properties of binders through machine learning (ML) based on the molecular simulation dataset. Firstly, 273 sets of GAP-BPS binder models under different conditions were formed based on 21 crosslinking degrees and 13 temperatures, and MD simulation and mechanical property simulation were carried out. Then, the initial conditions of molecular simulation (crosslinking degree, temperature) and structural parameters (free volume) were taken as features, and the bulk modulus and shear modulus were taken as labels to form the dataset. Three machine learning models were trained and evaluated based on this dataset to test their prediction performance. Based on the cross-validation results, the Tabular Prior Data Fitting Network (TabPFN) exhibits the highest average prediction values (the average R² for bulk modulus and shear modulus were 0.9684 and 0.8827, respectively). But the significance analysis reveals that TabPFN significantly outperforms the RF model only in predicting bulk modulus. In subsequent prediction tasks with smaller datasets, TabPFN achieves superior average prediction values compared with RF and XGBoost. Full article

An environmentally friendly synthesis of polysubstituted pyrroles in ionic liquid was achieved via a gold-catalyzed propargylic substitution/hydration/amination/cycloisomerization sequence. Treatment of propargylic alcohols, 1,3-dicarbonyl compounds, and arylamines in the presence of AuBr₃ (5 mol%) and AgOTf (15 mol%) in [EMIM][NTf₂] afforded polysubstituted pyrroles in good to high yield. This reaction involves reacting arylamine with the hydrated propargylic substitution product formed as an intermediate to yield polysubstituted pyrroles. Full article

The separation of rare earth elements (REEs) with similar chemical properties remains a relevant challenge today, most often addressed using liquid–liquid and solid-phase extraction with various chelating agents. Excellent complexing agents for REEs are 1,3-diketones and their analogs. We have for the first time proposed a method for preparing a material consisting of a covalently immobilized 3-acyl-4-hydroxycoumarin ligand on silica. For its synthesis, we employed a strategy based on the “click” reaction of 3-azidopropyl silica with a propargyl-containing coumarin–chalcone conjugate—this approach is the most tolerant and does not affect the coordinationally active fragment of the ligand. The material was characterized by thermal analysis, IR spectroscopy, and ¹³C NMR. The potential of the synthesized material for REE preconcentration was demonstrated at pH 5–5.5: high extraction efficiency for Gd(III), Dy(III), Er(III), Eu(III), Sm(III), and Yb(III) was observed, with fast adsorption kinetics (30 min) and extraction degrees of ~98%. Under unified conditions of static and dynamic extraction for Gd(III), Dy(III), Er(III), Eu(III), Sm(III), and Yb(III), affinity series toward the surface were obtained as a function of the distribution coefficient. It was shown that 10-fold molar excesses of Fe(III), Al(III), Cu(II), Ni(II), and Co(II) allow retention of more than 95% extraction for Dy(III) and Er(III). After adsorption of Dy(III) and Er(III), shifts in the carbonyl group absorption bands are visible in the IR spectra of the material, indicating a chelating mechanism of sorption. Additional studies are required for implementation in analytical and preparative REE separation schemes; however, preliminary data show that the material is a highly active adsorbent. Full article

A symmetrical rubrene derivative, 5,6-bis(4-(methoxycarbonyl)phenyl)-11,12-diphenyltetracene, was synthesized via the thermal dimerization of 1,1-diphenyl-3-[4-(methoxycarbonyl)phenyl]-3-chloroallene. The reaction proceeded with the low selectivity typical of the classical “rubrenic synthesis” under these conditions, affording the target tetracene and the bis(alkylidene)cyclobutene by-product in nearly equal yields of 25% each. The optical characteristics of this rubrene derivative were investigated, revealing bright orange fluorescence in a CHCl₃ solution (λ_em = 565 nm, Φ_F = 0.81, τ = 11.41 ns), which is strongly quenched in the solid state (Φ_F = 0.01) due to aggregation. Full article

We report an efficient and transition-metal-free protocol for the propargylation of 4-(4-chlorophenyl)-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile using propargyl bromide in the presence of cesium carbonate in dimethylsulfoxide under mild conditions. This synthetic transformation proceeds with marked chemoselectivity, furnishing the O-propargylated pyridine and the N-propargylated 2-pyridone in 75% and 8% yields, respectively. Both products were fully characterized by IR and NMR spectroscopy, as well as high-resolution mass spectrometry, confirming their molecular structures. Full article

Methylbutynol (MB) is a typical propargylic alcohol with both alkynyl and hydroxyl groups, featuring excellent modifiability and broad applications. Currently, it is produced through the reaction of alkaline metallic acetylides and acetone, requiring expensive raw material and harsh reaction conditions. Herein, a novel method was proposed by replacing the metallic acetylide with calcium carbide (CaC₂) as a low-cost industrial acetylide reagent. The effects of solvent, activator, and proton donor on the ball mill reaction, and the defoaming performance of the resultant MB and its oxidative coupling product (2,7-dimethyl-3,5-octadiyn-2,7-diol), were studied. Nucleophilic reactivity of CaC₂ with acetone can be regulated by the activating effect of the ball mill, an appropriate activator, and a proton donor. High yield of MB (~94%) was obtained under synergistic action of TBAF·3H₂O and acetylene, which represents a facile synthesis process of MB under mild conditions. MB exhibits good defoaming performance, and 2,7-dimethyl-3,5-octadiyn-2,7-diol is more promising, being an excellent non-ionic defoamer. The result is of great significance for exploring new chemical reactions of CaC₂ and its high-value utilizations. Full article

Ferrocenium catalysis is a growing field of research. This study investigates the catalytic activity of different ferrocenium salts in propargylic substitution reactions to afford propargylic ethers. Four different ferrocenium catalysts were employed in the title reaction, which was monitored over time. The rate of the disappearance of the starting material can be fitted to a first order rate law and observed rate constants were determined. The catalyzed propargylic substitution reactions display a moderate but discernible dependence on the ferrocenium counterion. The lack of an induction period for the reaction indicates that the ferrocenium cation itself is catalytically active, and not just a decomposition product thereof, which would result in an induction period. The presence of a carboxylic acid substituent on one of the cyclopentadienyl rings enhances catalytic activity. The Meyer–Schuster rearrangement of the propargylic alcohol to the corresponding conjugated enone played only a minor role in the ferrocenium-catalyzed reactions. Catalyst decomposition moderately retards the reaction but does not suppress product formation, as demonstrated by experiments with aged FcBF₄. In contrast, the presence of TEMPO as a radical scavenger completely inhibits product formation, while not causing detectable catalyst decomposition at room temperature. In turn, FeCl₃ catalyzes both the propargylic substitution and the Meyer–Schuster rearrangement equally and decomposes the catalysis product over time. These findings reinforce the notion that strong Lewis acids readily promote the rearrangement of propargylic alcohols and that Lewis acidity plays a crucial role in finding a balance between the substitution reactions of propargylic alcohols and their rearrangement to unsaturated aldehydes. Full article

Vinylallenes have been used in Diels–Alder reactions with a variety of dienophiles. However, vinylallenes activated at the allenic part of the molecule have been reacted only with carbon–carbon double bonds. We prepared siloxy vinylallenes by the base-induced equilibrium of silyl-protected allyl-propargyl alcohols. We found that these systems react with imines to form cycloadducts with total regio and facial selectivity, but only moderate endo:exo selectivity. The cycloadducts obtained were transformed into indolizidine derivatives. The reaction was studied computationally using DFT and compared to the reaction of siloxydienes. It was found that the main difference between those systems is the higher nucleophilicity of the siloxydienes compared to the siloxy vinylallenes. Full article

2-Oxazolines are five-membered heterocyclic compounds with significant biological properties. They also play an important role in organic synthesis, acting as chiral ligands and protecting groups for hydroxyamino acids and amino alcohols. Poly(2-oxazolines) are known coating materials, for example, in biomedicine. Classic synthetic methods of 2-oxazolines involve a dehydrative cyclisation reaction between amino alcohols and carboxylic acids, acid chlorides, nitriles, imidates, and aldehydes. However, the electrophilic intramolecular cyclization of unsaturated amides is becoming an increasingly important synthetic method for the preparation of 2-oxazolines. This brief review summarizes procedures for synthesizing oxazolines using the electrophilic intramolecular oxidative cyclisation of N-allyl and N-propargyl amides, as published between 2014 and 2024. It covers the synthesis of 5-halomethyl-, 5-trifluoromethyl-, 5-sulfonylmethyl-, 5-sulfenylmethyl-, 5-selenylmethyl-, 5-acetoxymethyl-, 5-hydroxymethyl-, 5-aminomethyl-, 5-alkilo-, and 5-alkylideneoxazolines. Full article

Background/Objectives: Numerous studies have demonstrated that dietary plant-derived polyphenols suppress signaling and metabolic pathways in various malignancies, including neuroblastoma. In the present study, we compared the inhibitory activities of selected polyphenols and their combinations on key metabolic and signaling pathways in two human neuroblastoma cell lines and two noncancerous cell lines—mesenchymal stem cells (MSCs). Methods: The influence of polyphenols on neuroblastoma cells and MSCs were studied via an MTT-assay, cell cycle analysis, and an apoptosis assay (flow cytometry). Chou-Talalay algorithms were used to quantify drug interactions. SeaHorse energy profiling was applied to study energy metabolism. The influence of the compounds on metabolic enzymes and signaling pathways was examined using immunoblotting. Total protein biosynthesis was assessed using o-propargyl-puromycin labeling (flow cytometry). Results: While most of the studied polyphenols displayed a more significant inhibitory effect on neuroblastoma cells than on mesenchymal stem cells (MSCs), we found that the combinations of curcumin and quercetin (CQ) and curcumin, quercetin, and resveratrol (CQR) were significantly superior to the individual compounds. These combinations displayed synergistic effects and inhibited the cell cycle while inducing apoptosis. The CQ and CQR combinations effectively suppressed metabolic reprogramming by downregulating key enzymes of glycolysis, respiration, one-carbon metabolism, glutaminolysis, and fatty acid biosynthesis, as well as N-Myc and c-Myc, which are master regulators of metabolic processes. Furthermore, CQ and CQR inhibited AKT/mTOR, MAPK/ERK, and WNT/β-catenin signaling pathways and total protein biosynthesis and sensitized malignant cells to doxorubicin. Conclusions: Polyphenol combinations exert multifaceted inhibitory effects on metabolic rewiring and signaling networks in neuroblastoma cells. Full article

Methacrylyl-CoA is a key metabolic intermediate in the valine catabolic pathway. Its accumulation has been found to be cytotoxic and associated with pathological conditions. Nevertheless, detailed biological effects of methacrylyl-CoA and methacrylate in human physiology and pathology are poorly understood. We propose that the electrophilicity of the alkene bond in the methacrylyl group can react with the cysteine residues in proteins resulting in an unexplored protein post-translational modification (PTM), cysteine S-2-carboxypropylation (C2cp). To test and validate this mechanistic hypothesis, we experimentally detected and profiled S-2-carboxypropylated proteins from the complex cellular proteome with the design and application of a bioorthogonal chemical probe, N-propargyl methacrylamide. We tested the probe in different mammalian cell models and demonstrated its versatility and sensitivity to protein cysteine S-2-carboxypropylation. We established quantitative chemical proteomics for global and site-specific profiling of protein S-2-carboxypropylation, which successfully identified 403 S-2-carboxypropylated proteins and 120 cysteine modification sites from HEK293T cells. Through bioinformatic analysis, we found that C2cp-modified proteins were involved in a variety of critical cellular functions including translation, RNA splicing, and protein folding. Our chemoproteomic studies demonstrating the proteome-wide distribution of cysteine S-2-carboxypropylation provide a new biochemical mechanism for the functional investigation of methacrylyl-CoA and understanding valine-related metabolic disorders. Full article

Background/Objectives: The herbicide resistance of blackgrass (Alopecurus myosuroides Huds.) is one of the most serious problems in the winter cereal monoculture in Europe. Recently, Greek farmers expressed complaints of reduced susceptibility of this weed to winter wheat herbicides. Keeping this in mind, this study focused on the investigation of blackgrass resistance to herbicides at both phenotypic and molecular levels. Methods: Whole-plant rate-response pot assays were conducted to study the possible evolution of resistance (cross- or multiple-resistance) in a blackgrass population to ACCase- and ALS-inhibiting herbicides. Analysis of the ACCase gene sequence, herbicide metabolism study and competition with winter wheat studies were also conducted. Results: High levels of cross-resistance mainly to the ACCase post-emergence clodinafop-propargyl, medium to fenoxaprop-P-ethyl, cycloxydim, pinoxaden, as well as lower levels of resistance to ALS-inhibitors (mesosulfuron-methyl + iodosulfuron-methyl-sodium and pyroxsulam) were confirmed. In addition, the pre-emergence soil-applied herbicides chlorotoluron + diflufenican and prosulfocarb provided excellent control of the S and R blackgrass populations. The analysis of the ACCase gene sequence revealed a point mutation at position 1781, resulting in an amino acid substitution from isoleucine (Ile) to leucine (Leu). Furthermore, the combined application of the herbicides with piperonyl butoxide (PBO, applied 2 h before herbicide application) indicated that there was herbicide metabolism, which may be mediated by cytochrome P450. The R blackgrass population, when grown in competitive interaction with winter wheat, produced more tillers and aboveground fresh weight compared to the S population and caused greater reduction in winter wheat. Conclusions: The results suggest that a blackgrass population has developed multiple resistance to ACCase- and ALS-inhibiting herbicides, due to ACCase gene mutation and herbicide metabolism. No fitness cost and no compromised competitive ability associated with the blackgrass resistance were observed. Full article

Cytisine, a naturally occurring alkaloid and partial agonist of nicotinic acetylcholine receptors (nAChRs), has long been used as a smoking cessation aid and serves as the pharmacophore for varenicline. Recent research has expanded its therapeutic scope to neurodegenerative and neurological disorders, motivating the development of new cytisine derivatives. Among these, N-propargylcytisine combines the biological activity of the parent compound with the synthetic versatility of the terminal alkyne group. Herein, we report the synthesis and characterization of N-propargylcytisine, and its symmetrical dimer linked through 1,3-diyne moiety obtained via a copper-mediated Glaser–Hay oxidative coupling. The products were analyzed by NMR, FT-IR, and mass spectrometry, confirming the introduction of the propargyl moiety and the formation of the diyne bridge. Solvatochromic study of both compounds were performed using UV-VIS absorption spectroscopy in solvents of varying polarity, including protic solvents capable of hydrogen bonding. The 1,3-diyne motif, commonly found in bioactive natural products, endows the resulting dimer with potential for further derivatization and biological evaluation. This study demonstrates the utility of the Glaser–Hay reaction in the functionalization of alkaloid scaffolds and highlights the prospects of N-propargylcytisine derivatives in drug discovery targeting the central nervous system. Full article