Search Results (875)

A synthetic methodology of the CuAAC “click” approach was exploited for the construction of 1,2-azolyltriazole quinine derivatives by the reaction of O-propargylquinine with azidomethyl-1,2-azoles in methanol. Quinine–piperidine and quinine–anabasine conjugates were obtained using a chloroacetate linker by reacting quinine chloroacetate with piperidine or anabasine in a diethyl ether medium. Cinchophene ester was obtained by the acylation of quinine with cinchophen acid chloride in methylene chloride. The antibacterial, fungicidal, analgesic and cytotoxic properties of the obtained compounds were examined. Full article

The purpose of this work was to study the effects of lactoferrin (Lf) on acute (days 3 and 15) and early-delayed (day 30) changes in the dentate gyrus of mouse hippocampus caused by whole-body gamma-irradiation. Male C57BL/6 mice received Lf (4 mg per mouse, i.p. injection) immediately after whole-body gamma-irradiation at a dose of 7.5 Gy from a ⁶⁰Co source. The effect of Lf on mouse behavior was evaluated using “Open field” and “Elevated plus-maze” tests. The proportion of cells with DNA replication was determined by 5-ethynyl-2′-deoxyuridine incorporation (thymidine analog) and detected by a click reaction with azide Alexa Fluor 568. Lf treatment increased animal survival during the experiment (30 days), compensated for radiation-induced body weight loss, and prevented suppression of motor and exploratory activities. A pronounced anti-radiation effect of Lf on mouse brain cells has been demonstrated. A single injection of the protein allowed preserving 2-fold more proliferating cells and immature neurons in the dentate gyrus of the hippocampus of irradiated animals during the acute period of post-radiation injury development. Full article

As a novel carbon material, multi-walled carbon nanotubes (MWCNTs) have attracted significant research interest in energetic applications due to their high aspect ratio and exceptional physicochemical properties. However, their inherent structural characteristics and poor dispersion severely limit their practical utilization in solid propellant formulations. To address these challenges, this study developed an innovative reverse-engineering strategy that precisely confines MWCNTs within a three-dimensional Fe₂O₃ gel framework through a controllable sol-gel process followed by low-temperature calcination. This advanced material architecture not only overcomes the traditional limitations of MWCNTs but also creates abundant Fe-C interfacial sites that synergistically catalyze the thermal decomposition of glycidyl azide polymer-based energetic thermoplastic elastomer (GAP-ETPE). Systematic characterization reveals that the MWCNTs@Fe₂O₃ nanocomposite delivers exceptional catalytic performance for azido group decomposition, achieving a >200% enhancement in decomposition rate compared to physical mixtures while simultaneously improving the mechanical strength of GAP-ETPE-based propellants by 15–20%. More importantly, this work provides fundamental insights into the rational design of advanced carbon-based nanocomposites for next-generation energetic materials, opening new avenues for the application of nanocarbons in propulsion systems. Full article

Nano- (NPs) and microplastics (MPs) are ubiquitous and raising concerns about their toxicity. A popular model for studying acute toxicity is Danio rerio. This study investigated the acute toxicity in FET test of polystyrene nanoparticles (500 nm, nanoPS) at different concentrations (0.01, 0.1, and 0.2 mg/mL), with different surface groups (non-modified, amine, carboxyl) and discuss the toxicological contribution of commercially added compounds. Different behavioural tests were used to investigate the neurotoxicity of nanoPS and sodium azide: coiling assay test, light–dark preference test, and colour preference test. Sodium azide and other preservatives are often present in commercially available NP and MP solutions frequently used in microplastic toxicity tests, but their effects on the results remain largely unknown. In the FET test, nanoPS did not increase mortality or affect the heart rate or body length. A higher hatching rate was observed at 48 hpf. Although nanoPS showed no acute toxicity, behavioural tests revealed subtle neurotoxic effects (changes in colour preference), suggesting a potential impact on neurological function. Additionally, sodium azide exhibited toxicity, indicating that additives may confound toxicity assessments. This highlights the need for careful consideration of preservatives in nanoparticle research to avoid misleading conclusions. Full article

As eco-friendly processes become central to modern organic synthesis, plant-based materials are emerging as attractive alternatives for both nanoparticle fabrication and catalysis. In this study, we explore the use of clove extract, a natural and renewable resource, for the green synthesis of copper oxide (CuO) nanoparticles and their subsequent application in organic transformations. Clove extract was employed to reduce copper chloride via a simple co-precipitation method under mild conditions, yielding CuO nanoparticles characterized by XRD, FTIR, and SEM-EDX techniques. These nanoparticles were then used as catalysts in the copper-catalyzed azide–alkyne cycloaddition (CuAAC) to afford eugenol-based 1,2,3-triazoles in excellent yields. This dual use of clove extract exemplifies a sustainable approach that merges natural product valorization with efficient catalysis for triazole synthesis. Full article

In the present study, for the first time, a biodegradable and non-toxic polyphosphoramidate glycohydrogel (PPAGHGel) was prepared by crosslinking a polyphosphoramidate glycoconjugate (PPAG) with hexamethylene diisocyanate (HMDI) under mild conditions. Poly(oxyethylene H-phosphonate) (POEHP) was used as a precursor and was converted into PPAG via the Staudinger reaction with glucose-containing azide (2-p-azidobenzamide-2-deoxy-1,3,4,6-tetra-O-trimethylsilyl-α-D-glucopyranose). Then, crosslinking of PPAG was performed to yield PPAGHGel, which was thoroughly characterized. The gel showed a gel fraction of 83%, a swelling degree of 1426 ± 98%, and G″ = 1560 ± 65 Pa. The gel was fully degraded by alkaline phosphatase (400 U/L, pH 9) in 19 days, while hydrolytically, up to 52% degradation was observed under similar conditions. Multivalent studies of the obtained hydrogel with lectin–Concanavalin A were performed. PPAGHGel binds 92% of Concanavalin A within 24 h and the complex remains stable until the amount of glucose reaches 0.3 mM. PPAGHGel acts as a stabilizer for silver nanoparticles (12 nm). SEM shows pores measuring 10 µm (surface) and 0.1 mm (interior) with capillary channels, confirming the gel’s suitability for biosensors, drug delivery, or wound dressings. The cytotoxic (IC50) and cell-adhesive properties of the obtained hydrogel were investigated on human cell lines (HeLa). Antibacterial activity tests were also performed with gel containing silver nanoparticles against skin-associated pathogenic bacteria. The results show that PPAGHGel possesses excellent biocompatibility, non-adhesive properties and antibacterial activity. Full article

Estradiol (E2) plays an important role in cell proliferation and certain brain functions. To reveal its mechanism of action, its detectability is essential. Only a few fluorescent-labeled hormonally active E2s exist in the literature, and their mechanism of action usually remains unclear. It would be of particular interest to develop novel labeled estradiol derivatives with retained biological activity and improved optical properties. Due to their superior optical characteristics, aza-BODIPY dyes are frequently used labeling agents in biomedical applications. E2 was labeled with the aza-BODIPY dye at its phenolic hydroxy function via an alkyl linker and a triazole coupling moiety. The estrogenic activity of the newly synthesized fluorescent conjugate was evaluated via transcriptional luciferase assay. Docking calculations were performed for the classical and alternative binding sites (CBS and ABS) of human estrogen receptor α. The terminal alkyne function was introduced into the tetraphenyl aza-BODIPY core via selective formylation, oxidation, and subsequent amidation with propargyl amine. The conjugation was achieved via Cu(I)-catalyzed azide–alkyne click reaction of the aza-BODIPY-alkyne with the 3-O-(4-azidobut-1-yl) derivative of E2. The labeled estrogen induced a dose-dependent transcriptional activity of human estrogen receptor α with a submicromolar EC₅₀ value. Docking calculations revealed that the steroid part has a perfect overlap with E2 in ABS. In CBS, however, a head-tail binding deviation was observed. A facile, fluorescent labeling methodology has been elaborated for the development of a novel red-emitting E2 conjugate with substantial estrogenic activity. Docking experiments uncovered the binding mode of the conjugate in both ABS and CBS. Full article

A series of eleven new N-alkyl 3-(3-benzyloxyquinoxalin-2-yl) propanamides were prepared based on the azide coupling of 3-(3-benzyloxyquinoxalin-2-yl) propanhydrazide with a variety of primary and secondary amines and the consequent conjunction of a broad spectrum of lipophile and hydrophile characters to a quinoxaline ring system. 3-(3-benzyloxyquinoxalin-2-yl) propanhydrazide was produced in a two-step reaction of methyl 3-(3-oxo-3,4-dihydroquinoxalin-2-yl) propanoate with benzyl chloride followed by the hydrazinolysis of the corresponding ester. The antiproliferative activity of the compounds was tested in various cancer cell lines, including PC-3, Hela, HCT-116, and MCF-7; they showed a wide spectrum of activity for most of the tested compounds. Compound 6k exhibited the highest activity, which was comparable to that of doxorubicin, with IC₅₀ (µM) values of 12.17 ± 0.9, 9.46 ± 0.7, 10.88 ± 0.8, and 6.93 ± 0.4 µM compared to 8.87 ± 0.6, 5.57 ± 0.4, 5.23 ± 0.3, and 4.17 ± 0.2 µM for doxorubicin against Hela, HCT-116, and MCF-7, respectively. The in silico mechanistic study revealed the inhibition of HDAC-6 through the binding of the unique zinc finger ubiquitin-binding domain (HDAC6 Zf-UBD). The docking results showed a specific binding pattern that emphasized the crucial role of the quinoxaline ring and its substituents. The newly developed derivatives were evaluated for antitumor effects against four cancer cell lines PC-3, HeLa, HCT-116, and MCF-7. This research led to the identification of a quinoxaline-based scaffold exhibiting broad-spectrum antiproliferative activity and a distinct mechanism involving binding to HDAC6 Zf-UBD. The findings highlight its potential for further optimization and preclinical studies to support future anticancer drug development. Full article

Mechanochemical and transition-metal-catalyzed reactions of alkynes, exhibiting significant advantages like short reaction time, solvent-free, high yield and good selectivity, were considered to be green and sustainable pathways to access functionalized molecules and obtained increasing attention due to the superiorities of mechanochemical processes and the reactivities of alkynes. The ball milling and CuI-catalyzed Sonogashira coupling of alkyne and aryl iodide avoided the use of common palladium catalysts. The mechanochemical Rh(III)- and Au(I)-catalyzed C–H alkynylations of indoles formed the 2-alkynylated and 3-alkynylated indoles selectively. The mechanochemical and copper-catalyzed azide-alkyne cycloaddition (CuAAC) between alkynes and azides were developed to synthesize 1,2,3-triazoles. Isoxazole could be formed through ball-milling-enabled and Ru-promoted cycloaddition of alkyne and hydroxyimidel chloride. In this review, the generation of mechanochemical and transition-metal-catalyzed reactions of alkynes was highlighted. Firstly, the superiority and application of transition-metal-catalyzed reactions of alkynes were briefly introduced. After presenting the usefulness of green chemistry and mechanochemical reactions, mechanochemical and transition-metal-catalyzed reactions of alkynes were classified and demonstrated in detail. Based on different kinds of reactions of alkynes, mechanochemical and transition-metal-catalyzed coupling, cycloaddition and alkenylation reactions were summarized and the proposed reaction mechanisms were disclosed if available. Full article

Non-isothermal calorimetry is performed to study the kinetics of metal-free A₂/B₂-type azide–alkyne polyaddition between the dipropargyl ether of bisphenol A with different organic diazides. The diazide structure is varied to probe the effect of the nature of a hydrocarbon spacer between the azide groups on their reactivity. Isoconversional analysis demonstrates that the polymerization processes are characterized by the same activation energy of 84 kJ mol⁻¹ for all studied diazides. It is found that diazides with aromatic spacers demonstrate ~1.6 times higher reactivity than that of diazides with the alkyl spacer. The difference in the reactivity is explained by the difference in the electronic effects of the hydrocarbon spacers on the azide groups as well as by the difference in their steric availability. The veracity of the obtained kinetic parameters is validated by a polymerization test at the time–temperature conditions predicted from the obtained kinetic data followed by independent assessment of the monomer conversion using FTIR. Full article

The synthesis of novel biodegradable polymers as non-viral vectors remains one of the challenging tasks in the field of gene delivery. In this study, the synthesis of the polysaccharide-g-polypeptide copolymers, namely, hyaluronic acid-g-polylysine (HA-g-PLys), using a copper-free strain-promoted azide-alkyne cycloaddition reaction was proposed. For this purpose, hyaluronic acid was modified with dibenzocyclooctyne moieties, and poly-L-lysine with a terminal azido group was obtained using ring-opening polymerization of N-carboxyanhydride of the corresponding protected amino acid, initiated with the amino group azido-PEG₃-amine. Two HA-g-PLys samples with different degrees of grafting were synthesized, and the structures of all modified and synthesized polymers were confirmed using ¹H NMR and FTIR spectroscopy. The HA-g-PLys samples obtained were able to form nanoparticles in aqueous media due to self-assembly driven by electrostatic interactions. The binding of DNA and model siRNA by copolymers to form polyplexes was analyzed using ethidium bromide, agarose gel electrophoresis, and SybrGreen I assays. The hydrodynamic diameter of polyplexes was ˂300 nm (polydispersity index, PDI ˂ 0.3). The release of a model fluorescently-labeled oligonucleotide in the complex biological medium was significantly higher in the case of HA-g-PLys as compared to that in the case of PLys-based polyplexes. In addition, the cytotoxicity in normal and cancer cells, as well as the ability of HA-g-PLys to facilitate intracellular delivery of anti-GFP siRNA to NIH-3T3/GFP+ cells, were evaluated. Full article

Laser propulsion is a new conceptual technology that drives spacecraft and possesses advantages such as high specific impulse, large payload ratio, and low launch cost. It has potential applications in diverse areas, such as space debris mitigation and removal, microsatellite attitude control, and orbital maneuvering. Liquid pulse laser propulsion has notable advantages among the various laser propulsion systems. We review the concept and the theory of liquid laser propulsion. Then, we categorize the current state of research based on three types of propellants—non-energetic liquids, energetic liquids, and liquid metals—and provide an analysis of the propulsion characteristics arising from the laser ablation of liquids such as water, glycidyl azide polymer (GAP), hydroxylammonium nitrate (HAN), and ammonium dinitramide (ADN). We also discuss future research directions and challenges of pulsed liquid laser propulsion. Although experiments have yielded encouraging outcomes due to the distinctive properties of liquid propellants, continued investigation is essential to ensure that this technology performs reliably in actual aerospace applications. Consistent results under both spatial and ground conditions remain a key research content for fully realizing its potential. Full article

β-Lactosylceramide (β-LacCer) is not only a key intermediate in the biosynthesis of complex glycosphingolipids (GSLs) but also an important regulator of many biological processes. To facilitate the investigation of β-LacCer and other GSLs, a series of β-LacCer analogs with an azido group at the 6-C-position of the D-galactose in lactose and varied forms of the ceramide moiety were synthesized from commercially available lactose in sixteen linear steps by a versatile and diversity-oriented strategy, which engaged lipid remodeling and glycan functionalization at the final stage. These azide-labeled β-LacCer analogs are flexible and universal platforms that are suitable for further functionalization with other molecular tags via straightforward and biocompatible click chemistry, thereby paving the way for their application to various biological studies. Full article

6-Aryl-7H-pyrrolo[2,3-d]pyrimidin-4-amines have promising properties as colony-stimulating factor 1 receptor (CSF1R) inhibitors. Inspired by these antagonists, two series of 1,2,3-triazole analogues (28 compounds) were synthesized and evaluated as CSF1R inhibitors. Enzymatic IC₅₀ profiling showed that 27 of the 28 derivatives had lower IC₅₀ than the reference drug PLX-3397. Three derivatives displayed CSF1R Ba/F3 cellular IC₅₀ well below 1 µM. Profiling of the most promising triazole analogue (compound 27a) toward a panel of kinases reveals a high selectivity for CSF1R with respect to its family kinases, but 27a also inhibits ABL, SRC, and YES kinases. Molecular docking of 27a toward two CSF1R X-ray structures identified two different ligand-inverted binding poses, which triggers interest for further investigations. Full article

A novel and general approach to the practical ROMP polymerization of cinchona alkaloid derivatives providing novel hybrid materials having quinine attached on a poly(norbornene-5,6-dicarboxyimide) matrix is presented. The concept involves an easy modification of quinine (in general, any cinchona alkaloid) toward clickable 9-azide that reacts with N-propargyl-cis-5-norbornene-exo-2,3-dicarboxylic imide in Cu(I)-catalyzed Huisgen cycloaddition (click chemistry). The resulting monomers undergo a controllable ROMP reaction that leads to novel polymers of a desired length and solubility. This sequence allows for the facile preparation of a regularly decorated polymeric material having one quinine moiety per single mer of the polymer chain inaccessible using typical immobilization methods. A poly(norbornene-5,6-dicarboxyimide) type of polymeric matrix was selected due to the high reactivity of the exo-norbornene motif in Ru(II)-catalyzed ROMP and its chemical and thermal stability as well as convenient, scalable access from inexpensive cis-5-norbornene-exo-2,3-dicarboxylic anhydride (‘one-pot’ Diels–Alder reaction of dicyclopentadiene and maleic anhydride). An appropriate combination of a Grubbs catalyst, Ru(II) (G1, G2), and ROMP conditions allowed for the efficient synthesis of well-defined soluble polymers with mass parameters in the range Mn = 2.24 × 10⁴ – 2.26 × 10⁴ g/mol and Mw = 2.90 × 10⁴–3.05 × 10⁴ g/mol with good polydispersity, Đ_M = 1.32–1.35, and excellent thermal stability (up to 309°C T_d10). Spectroscopic studies (NMR and electronic circular dichroism (ECD)) of these products revealed a linear structure with the slight advantage of a trans-configuration of an olefinic double bond. The resulting short-chain polymer discriminates mandelic acid enantiomers with a preference for the (R)-stereoisomer in spectrofluorimetric assays. This concept seems to be rather general with respect to other molecules dedicated to incorporation into the poly(norbornene-5,6-dicarboxyimide) chain. Full article