Search Results (162)

This study investigates how phospholipid headgroups influence passive membrane penetration and structural impact of four nitrogen-, sulfur-, and oxygen-containing heterocycles (NSO-HETs)—N-methyl-2-pyrrolidone (PIR), 1,4-dioxane (DIOX), oxane (OXA), and phenol (PHE). Using all-atom molecular dynamics simulations combined with Accelerated Weight Histogram free energy calculations, the passive transport of NSO-HETs across DPPC, DPPE, DPPA, and DPPG bilayers was characterized. DPPG showed the highest membrane affinity, increasing permeability (logP_memb/bulk) by 27–64% compared to DPPE, associated with the lowest permeability and tightest lipid packing. Free energy barriers are also decreased in DPPG relative to DPPE; PIR’s central barrier dropped from 19.2 kJ/mol (DPPE) to 16.6 kJ/mol (DPPG), while DIOX’s barrier decreased from 7.2 to 5.2 kJ/mol. OXA exhibited the lowest central barriers (1.2–2.2 kJ/mol) and uniquely accumulated at higher concentrations in the bilayer center than in bulk water, with free energy ranging from −3.4 to −5.9 kJ/mol. PHE and OXA caused significant bilayer thinning (up to 11%) and reduced lipid tail order, especially in DPPE and DPPA. Concentration effects were most pronounced in DPPE, where high solute loading disrupted lipid order and altered free energy profiles. These results highlight the crucial role of headgroup identity in modulating NSO-HET membrane permeability and structural changes. Full article

Balancing the energy and stability of energetic materials is a challenging task in their development. Salt formation is a promising strategy for seeking high-energy, low-sensitivity materials. In this study, the modification of anions facilitates the enhancement of density and oxygen balance in amino-functionalized N-heterocycle systems. The results of single-crystal X-ray diffraction and theoretical analysis suggest that DATOP possesses intense hydrogen bonding networks in its crystal structure. The ideal structure of DATOP (ρ = 1.954 g·cm⁻³, D = 8624 m·s⁻¹, P = 34.4 GPa) gives rise to higher detonation properties compared to DATOC (ρ = 1.717 g·cm⁻³, D = 5984 m·s⁻¹, P = 12.4 GPa). In particular, the thermal stability of DATOP (T_d = 273 °C) is superior to DATOC (T_d = 154 °C). DATOP also maintains comparable mechanical sensitivities to DATOC. These fascinating results reveal that the strategy of salt formation shows excellent potential for balancing energy and stability in energetic materials. Full article

Heterocycles—cyclic compounds containing at least one non-carbon heteroatom (e.g., N, O, S)—are fundamental in medicinal chemistry due to their influence on a drug’s physicochemical and biological properties. They improve solubility, bioavailability, and facilitate molecular recognition through their electronic and hydrogen-bonding features. These properties make them indispensable in drug design. This study focuses on the synthesis of a key heterocyclic intermediate: benzyl-N-[4-(2-hydroxyethyl)-1,3-thiazol-2-yl]carbamate. This molecule incorporates a thiazole ring, known for its rigidity and electronic properties, that enhances target interactions. The 2-position bears a Cbz-protected amine, enabling orthogonal deprotection, while the 4-position features a hydroxyethyl side chain, providing a handle for further chemical modifications via nucleophilic substitution. Herein, we report the successful synthesis of this intermediate along with its full ¹H and ¹³C NMR spectra, melting point, and crystal structure, confirming its identity and purity. Full article

In this study, a C-C bond-linked triazole-fused oxadiazole energetic compound, 4-amino-5-(4-amino-1,2,5-oxadiazol-3-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one (1), was successfully designed and efficiently synthesized. Following nitration, a functional group-modified nitramine energetic compound (2) was obtained, and its energetic ionic salt (3) was further prepared. A comprehensive characterization of the structures of these three compounds was conducted, resulting in the successful elucidation of the single-crystal structures of compound 2·Ca²⁺·6H₂O and compound 3·MeOH. Compound 2 exhibited a positive formation enthalpy (56.2 kJ·mol⁻¹) and moderate mechanical sensitivity (FS = 120 N, IS = 12 J). Due to the presence of the nitramine group, compound 2 exhibited a relatively low thermal decomposition temperature (T_dec = 94 °C). However, the thermal stability of compound 3 was significantly improved (T_dec = 233 °C), which is attributed to salt formation. Compound 3 exhibits a positive formation enthalpy (121.0 kJ·mol⁻¹), along with excellent detonation performance (D = 8120 m·s⁻¹, P = 32.1 GPa) and reduced mechanical sensitivity (FS = 224 N, IS = 24 J). Therefore, the multi-heterocyclic compound, joined via C-C bond linkage, demonstrates outstanding performance, offering a new avenue for the design and synthesis of energetic materials. Full article

Neurodegenerative diseases (NDDs), including Alzheimer’s disease (AD) and Parkinson’s disease (PD), are characterized by progressive neuronal dysfunction and loss and represent a significant global health challenge. Oxidative stress, neuroinflammation, and neurotransmitter dysregulation, particularly affecting acetylcholine (ACh) and monoamines, are key hallmarks of these conditions. The current therapeutic strategies targeting cholinergic and monoaminergic systems have some limitations, highlighting the need for novel approaches. Metallodrugs, especially ruthenium and platinum complexes, are gaining attention for their therapeutic use. Among metal complexes, gold(I) and silver(I) N-heterocyclic carbene (NHC) complexes exhibit several biological activities, but their application in NDDs, particularly as monoamine oxidase (MAO) inhibitors, remains largely unexplored. To advance the understanding of this field, we designed, synthesized, and evaluated the biological activity of a new series of Au(I) and Ag(I) complexes stabilized by NHC ligands and bearing a carboxylate salt of tert-butyloxycarbonyl (Boc)-N-protected proline as an anionic ligand. Through in silico and in vitro studies, we assessed their potential as acetylcholinesterase (AChE) and MAO inhibitors, as well as their antioxidant and anti-inflammatory properties, aiming to contribute to the development of potential novel therapeutic agents for NDD management. Full article

The Maillard reaction is a complex chemical reaction that occurs between nucleophilic groups, such as thiolates or amino groups primarily from amino acids, peptides, proteins, and carbonyl groups, particularly from reducing sugars. The pH value of the medium is a key parameter controlling the kinetics of the Maillard reaction, as it influences the concentration of nucleophilic groups. Other specific conditions of reaction medium such as temperature, reaction time (or residence time in a process), and water activity also significantly influence the Maillard reaction. Understanding the impact of these parameters is essential for optimizing the Maillard reaction to enhance sensory attributes, nutritional qualities, and product stability during the storage and distribution of the final products. The Maillard reaction is responsible for the formation of desirable sensory qualities such as flavor, aroma, color, and texture in cooked and thermally processed foods, in addition to the improvement of nutritional value and shelf life of foods. In contrast, there are limitations in its industrial applications, as it can also generate harmful compounds such as acrylamide, N(6)-carboxymethyllysine, furans, and heterocyclic amines, as well as undesired changes in the nutritional value of the food. This review provides an overview of the Maillard reaction’s mechanism, influencing parameters, pros and cons, as well as some food industrial applications. Full article

N-Heterocyclic carbenes (NHCs) have been widely utilized over the past three decades due to their broad applications, yet synthetic methods for their preparation remain limited. A promising approach for NHC generation involves the thermolysis of NHC adducts. Herein, we report the synthesis of NHC pentafluorobenzene adducts featuring an o-carboranyl group in the backbone (2), which, unlike previously studied systems, resists thermal decomposition. Density functional theory (DFT) calculations were used to investigate the discrepancy, revealing that the decomposition reaction is kinetically controlled. For widely studied NHC systems like IMes and SIMes, the activation barriers were calculated to be 246.3 kJ/mol and 267.3 kJ/mol, respectively, aligning with reactions requiring heating. In contrast, the o-carborane system exhibited a significantly higher barrier of 320.5 kJ/mol, primarily due to the structural influence of the o-carborane backbone. Further analysis indicates that delocalization of π-electrons from the backbone into the NHC’s p-orbitals lowers the activation barrier, whereas delocalization into an exo-NHC ring increases it. These findings provide new insights into the thermal generation of NHCs and we hope it can offer guidance for future NHC design and synthesis. Full article

Background: 3-Lup-20(29)-ene-3β,28-diol (betulin, BN) is a natural bioactive compound with significant synthetic and pharmacological potential. A growing body of research highlights the increasing interest in BN and its derivatives, driven by their broad biological activities (anticancer, antibacterial, anti-inflammatory, antiretroviral). However, poor bioavailability and low intracellular accumulation limit its pharmaceutical application. Methods: A promising strategy to enhance BN’s therapeutic potential is glycoconjugation. This approach improves drug bioavailability, solubility, and selectivity, particularly in cancer therapy, by leveraging cancer cells’ heightened glucose demand and overexpression of glucose transporters. Incorporating an N-heterocyclic linker, such as a 1,2,3-triazole ring, further enhances biological activity. Results: We developed an efficient method for modifying the betulin backbone at position C28 with sugar units via a (CO)CH₂CH₂COOH linker, based on CuAAC, yielding ten new betulin glycoconjugates with good yields and purity confirmed by spectroscopic analysis (NMR, HRMS). The potential for inhibition of cancer cell proliferation (HCT-116 human colorectal carcinoma cell line and MCF-7 human breast cancer cell line) and cytotoxicity toward normal human dermal fibroblasts (NHDF-Neo) was assessed. Conclusions: The obtained glycoconjugates exhibited higher activity against MCF-7, indicating the selectivity of their action. The development of glycoconjugates based on increased glucose demand and overexpression of its transporters could be an interesting strategy for acquiring anticancer agents, combining innovative chemical solutions with biological complexity. Such an approach may be crucial in the effective fight against cancer diseases. Full article

This paper concerns the in silico studies of the influence of heterocyclic substituents as well as their protonated and deprotonated forms on the spectral characteristics of BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) dyes. Computational studies were carried out in order to reveal the most effective method of modeling of the spectral features of fluorescent BODIPY dyes. To perform these studies, the pyrrole and imidazole derivatives of BODIPY dyes were selected, and their spectral features were investigated with DFT and TD-DFT calculations. The calculations showed that the deprotonation of the substituents leads to a bathochromic shift of the calculated absorption wavelength, while the protonation (imidazole derivative) brings about a hypsochromic shift with respect to the neutral form of the dye. The calculated spectral characteristics, considering the influence of the solvent polarity (PCM model), were correlated with the ${\mathrm{E}}_{\mathrm{T}}^{\mathrm{N}}$ solvatochromic parameter. These correlations show that the increase in the solvent polarity causes a hypsochromic shift of the calculated absorption and emission wavelengths, whereas the bathochromic shift of the wavelengths is observed for the protonated form. Full article

In this study, catalytically active coatings on titanium were synthesized by plasma electrolytic oxidation (PEO) in aqueous electrolytes based on sodium tungstate with the addition of sodium phosphate or sodium borate and chelate complexes of iron, cobalt or nickel. Taking into account the EDX, XPS and XRD data, the oxide–phosphate coatings (PWFe, PWCo, PWNi) contained crystalline titanium oxide and amorphous tungstates and/or phosphates of iron triad metals. Amorphization was facilitated by high phosphorus concentrations (up to 6 at.%). Replacing phosphate with borate in the electrolyte with Ni(II)-EDTA complexes led to the crystallization of WO₃ and NiWO₄ in the PEO coatings (BWNi). All formed PEO coatings were active in reactions of the oxidative desulfurization (ODS) of thiophene and dibenzothiophene and oxidative denitrogenation (ODN) of pyridine, as well as in the simultaneous removal of S- and N-containing substrates from their mixture. The stability of samples with MWO₄ increased in the following series: PWNi < PWCo < PW < PWFe < BWNi. Replacing phosphate with borate in the electrolyte resulted in the preparation of catalysts with enhanced stability and activity. In contrast to PWM catalysts, the BWNi catalyst had selectivity toward the oxidation of pyridine in its mixture with thiophene. Full article

Exercise is one of the main challenges to the body’s homeostasis since it needs an immediate, substantial rise in ATP re-synthesis, which leads to the prevention of response capacity and performance of players. Therefore, it is vital to monitor sweat metabolites in soccer players during vigorous exercise to comprehend their functional variations. This flagged the requirement metabonomic approaches for the determination of the distinct metabolic pathways and signature metabolites that are involved in soccer players pre- and post-exercise. In this study, metabolomics and chemometrics approaches were integrated to accelerate and unravel signature-altered metabolites involved pre- and post-exercise. Metabolites profiling revealed a total of 57 signatures and the identified signature altered metabolites belonging to carboxylic acids, ketone, alcohols, aldehydes, aromatics, alkenes, hexoses, hydroxy fatty acids, tetracyclic N-heterocycles, aldopentose, benzenes, alkanes, phenols, and heterocyclic. Niacin is the most downregulated and abundant pre-induced exercise, which can employ its effects through energy metabolism as a precursor for nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). Significant alterations were also specifically observed in the Alanine, aspartate and glutamate, Valine, leucine and isoleucine, Pantothenate and CoA biosynthesis, and Galactose metabolisms following exercise. Full article

Polystyrene-supported chiral hydroxyamide-functionalized benzimidazolium chloride was synthesized by reacting Merrifield resin with a substituted-azole derived from (S)-leucinol. The combination of [IrCl(cod)]₂ and the resulting polymer-supported N-heterocyclic carbene (NHC) ligand precursor catalyzed the enantioselective reduction of ketones using (EtO)₂MeSiH under heterogeneous reaction conditions via a pre-mixing reaction procedure. Additionally, the solid-state resin could be easily recovered through simple filtration and the catalyst system’s reusability was evaluated. Full article

The Konduyak gold–quartz–sulfide deposit is one of the most promising gold mines in the Ayakhta gold ore cluster on the Yenisei ridge. This article is devoted to the study of the composition of the volatile compounds in the ore-forming fluid, since this is one of the key aspects in understanding the conditions of deposit formation. The compositions of the fluids that formed quartz and pyrite in the deposit ore zone were determined using Raman spectroscopy and pyrolysis-free gas chromatography–mass spectrometry. The study of the fluid inclusions in the minerals showed that complex C-H-O-S-N multi-component fluids formed the quartz–sulfide ore zones. A range of 232 to 302 various volatile compounds were found in the fluids. The mineralizing fluids mainly consist of H₂O (14.25–96.02 rel. %) and CO₂ (2.07–54.44 rel. %). A high SO₂ content (14.60–44.95 rel. %) is typical of fluids trapped by pyrites. Moreover, a wide range of hydrocarbons (oxygen-free aliphatic, cyclic, heterocyclic, and oxygenated) and nitrogenated and sulfur compounds were found among the volatiles in the fluid. The variable H/(H + O) ratios, from 0.51 to 0.81, and CO₂/(CO₂ + H₂O) ratios, from 0.02 to 0.56, indicate changes in the redox conditions during ore formation. Full article

The aim of this study was to synthesize new racemic and optically pure aryl-substituted purine bioisosteres using ultrasound-assisted Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition. Regioselective synthesis of α-azido alcohols was applied to afford heterocycles with a 2-hydroxyeth-1-yl linker. Catalytic asymmetric synthesis using halohydrin dehalogenase in the ring-opening of epoxides gave enantioenriched azido alcohols, which subsequently afforded R- and S-enantiomers of purine and pyrrolo[2,3-d]pyrimidines with a 1-hydroxyeth-2-yl linker. The newly synthesized compounds were evaluated in vitro for their antiproliferative activity against four malignant tumor cell lines. The influence of regioisomerism and the stereochemistry of the hydroxyethyl group, as well as a N-heterocyclic scaffold linked to the aryl moiety on cytostatic activity was evaluated. Of all the compounds tested, purine 40a and pyrrolo[2,3-d]pyrimidine 45a derivatives with p-trifluoromethyl-substituted aryl connected to 1,2,3-triazole via a 2-hydroxyeth-1-yl spacer showed promising submicromolar antiproliferative activity. In addition, compound 45a exhibited selectivity towards the tumor cell line, with a selectivity index (SI) of 40, moderate clearance, and good membrane permeability. Full article

We report in this contribution the synthesis and in vitro biological evaluation of a novel class of chiral thiazoloisoindolinone scaffolds as potent inhibitors against human farnesyltransferase (FTase-h). The targeted products, sulfides (4), sulfoxides (5,6), and sulfones (7), containing up to three points of diversification, were obtained in a short-step sequence starting from the available and cost-effective L-cysteine hydrochloride (1), which is the source of N and S atoms and the chiral pool, and α-carbonyl benzoic acids (2), which are isoindolinone precursors. Concisely, the key ester intermediates (1) provide (a) sulfide-amides (4) by solvent-free amidation, (b) sulfoxides (5,6) by selective S-oxidation using NaIO₄, and (c) sulfones (7) by oxidation using MMPP. Finally, the obtained N,S-acetal systems have shown promising inhibitory activities on FTase-h in the nanomolar range with excellent half maximal inhibitory concentration (IC₅₀) values up to 4.0 nanomolar (for example, 25.1 nM for sulfide 4bI, 67.3 nM for sulfone 7bG, and more interesting of 4.03 nM for sulfoxide 5bG). Full article