Search Results (759)

Post-translational modifications (PTMs) expand the structural diversity of proteins beyond the standard amino acids, influencing protein-protein interactions. Protein methylation, a prevalent PTM, involves the transfer of methyl groups from S-adenosylmethionine (SAM) to lysine and arginine residues. Arginine methylation is catalyzed by the Protein Arginine Methyltransferase (PRMT) family to yield mono- and dimethylarginine forms. PRMT1, the isozyme responsible for the majority of asymmetric dimethylation (ADMA) is implicated in various diseases, including cancer. Here, we report the synthesis and screening of a second-generation peptide library to identify novel PRMT1 substrates. The library, based on histone peptides, incorporated varying sequences of amino acids, facilitating substrate specificity studies. Screening identified 7 peptide sequences as exceptional PRMT1 substrates, which were confirmed by kinetic analysis. Consensus sequences revealed key recognition elements for PRMT1 catalysis, suggesting roles for small non-polar side chains and specific residues near the substrate arginine. Furthermore, we developed a peptide-based PRMT1 inhibitor by substituting the substrate arginine with a chloroacetamidine warhead. The inhibitor exhibited sub-micromolar inhibitory potency against PRMT1, surpassing previous peptide-based inhibitors. Our findings contribute to understanding PRMT1 substrate specificity and provide a scaffold for developing potent inhibitors targeting PRMT1 in diseases, including cancer. Full article

This paper introduces a modified soft margin optimal hyperplane (MSMOH) algorithm, which enhances the linear separating properties of support vector machines (SVMs) by placing higher penalties on large misclassification errors. This approach improves margin symmetry in both balanced and asymmetric data distributions. The research is divided into two main stages. The first stage evaluates MSMOH for synthetic data classification and its application in heart disease diagnosis. In a cross-validation setting with unknown data, MSMOH demonstrated superior average performance compared to the standard soft margin optimal hyperplane (SMOH). Performance metrics confirmed that MSMOH maximizes the margin and reduces the number of support vectors (SVs), thus improving classification performance, generalization, and computational efficiency. The second stage applies MSMOH as a novel synthesis algorithm to design a neural associative memory (NAM) based on a recurrent neural network (RNN). This NAM is used for fault diagnosis in fossil electric power plants. By promoting more symmetric decision boundaries, MSMOH increases the accurate convergence of 1024 possible input elements. The results show that MSMOH effectively designs the NAM, leading to better performance than other synthesis algorithms like perceptron, optimal hyperplane (OH), and SMOH. Specifically, MSMOH achieved the highest number of converged input elements $\left(1019\right)$ and the smallest number of elements converging to spurious memories $\left(5\right)$. Full article

Chiral coordination compounds are of growing interest due to their structural diversity and wide applicability. Besides chirality, alcohol and especially oxime-functionalized limonene derivatives confer water solubility, stability, and the appropriate reactivity to enable their use in asymmetric catalysis—such as allylic substitution, alkynylation, transfer hydrogenation, and selective C–C bond formation. Biologically, they have shown promising anticancer, antibacterial, and antibiofilm activity. This review presents an integrated overview of the synthesis, properties, and applications of chiral transition metal complexes featuring ligands derived from inexpensive, naturally occurring R- and S-limonene substrates, and explore their roles in catalysis and biological activity. Full article

The growing demand for sustainable and efficient synthetic methodologies has brought nanocatalysis to the forefront of modern organic chemistry, particularly in the construction of heterocyclic compounds through multicomponent reactions (MCRs). Among various nanocatalysts, calcium oxide nanoparticles (CaO NPs) have gained significant attention because of their strong basicity, thermal stability, low toxicity, and cost-effectiveness. This review provides a comprehensive account of the recent strategies using CaO NPs as heterogeneous catalysts for the green synthesis of nitrogen- and oxygen-containing heterocycles through MCRs. Key reactions such as Biginelli, Hantzsch, and pyran annulations are discussed in detail, with emphasis on atom economy, reaction conditions, product yields, and catalyst reusability. In many instances, CaO NPs have enabled solvent-free or aqueous protocols with high efficiency and reduced reaction times, often under mild conditions. Mechanistic aspects are analyzed to highlight the catalytic role of surface basic sites in facilitating condensation and cyclization steps. The performance of CaO NPs is also compared with other oxide nanocatalysts, showcasing their benefits from green metrics evaluation like E-factor and turnover frequency. Despite significant progress, challenges remain in areas such as asymmetric catalysis, industrial scalability, and catalytic stability under continuous use. To address these gaps, future directions involving doped CaO nanomaterials, hybrid composites, and mechanochemical approaches are proposed. This review aims to provide a focused and critical perspective on CaO NP-catalyzed MCRs, offering insights that may guide further innovations in sustainable heterocyclic synthesis. Full article

Chiral amines are vital structural motifs in pharmaceuticals and agrochemicals, where enantiomeric purity governs bioactivity and environmental behavior. We identified a novel (R)-selective amine transaminase (MwoAT) from Mycobacterium sp. via genome mining, which exhibits activity toward the synthesis of the chiral amine (R)-1-methyl-3-phenylpropylamine. The enzyme displayed optimal activity at pH 7.0 and 40 °C, with high thermostability and solvent tolerance. Using an AlphaFold3-guided semi-rational engineering strategy integrating molecular docking, alanine scanning, and saturation mutagenesis, residue L175 was pinpointed as critical for substrate binding. The resulting L175G variant exhibited a 2.1-fold increase in catalytic efficiency (k_cat/K_m) and improved thermal stability. Applied to the asymmetric synthesis of (R)-1-methyl-3-phenylpropylamine—a precursor for the antihypertensive drug dilevalol and potential scaffold for crop protection agents—the mutant achieved 26.4% conversion with ≥99.9% ee. The enzyme also accepted several ketones relevant to agrochemical synthesis, underscoring its versatility. This work delivers an engineered biocatalyst for sustainable chiral amine production and demonstrates an AI-assisted protein engineering framework applicable to both medicinal and agricultural chemistry. Full article

Background/Objectives: Watermelon (Citrullus lanatus) is a natural dietary source of L-citrulline and L-arginine, the two amino acids involved in nitric oxide (NO) production and vasodilation. Pre-clinical and clinical studies using isolated amino acids or watermelon extracts suggest blood pressure (BP)-lowering potential; however, limited research has been conducted on the impact of watermelon flesh (WM) on BP in adults at risk for hypertension. Therefore, the primary objective of this study was to assess the effect of daily WM intake for four weeks on 24 h ambulatory BP in adults with elevated blood pressure. The secondary outcomes of this study include changes in glucose and insulin markers, lipid profile, NO, L-citrulline, L-arginine, asymmetric dimethylarginine (ADMA) concentrations, and the L-arginine/ADMA ratio. Methods: In this randomized, placebo controlled parallel study design, 39 adults (age: 41 ± 14 years, BMI: 31 ± 6 kg/m², mean ± SD) with elevated BP were randomly assigned to one of three groups for a 4-week intervention: control (0 g WM), WM-1 cup (152 g/day), or WM-2 cups (304 g/day). Ambulatory BP was measured over 24 h at baseline and the end of the intervention period. Fasting plasma samples were analyzed for metabolic biomarkers on a clinical analyzer and NO using a colorimetric assay. L-citrulline, L-arginine, and ADMA were analyzed using an ultra-high-performance liquid chromatography triple quadrupole mass spectrometer (UHPLC-QQQ-MS/MS). Statistical analyses were conducted using SPSS software (IBM SPSS Statistics, Version 29.0.0). Results: After 4 weeks, mean 24 h ambulatory BP was 130.2 ± 3.9 mm Hg (control), 130 ± 3.2 mm Hg (WM-1 cup), and 124.9 ± 3.9 mm Hg (WM-2 cups), with no statistically significant differences between study interventions (p > 0.05). Similarly, no significant changes were observed in fasting plasma glucose, insulin, lipid profile, or NO concentrations. However, plasma L-arginine concentrations and L-arginine/ADMA ratios significantly increased in the WM groups compared to the control (p = 0.009) after adjusting for age, BMI, race, and gender in the statistical model. Conclusion: Overall, BP was not significantly different after two different doses of watermelon compared to control; however, improvements in NO synthesis pathway precursors (L-arginine, ADMA) suggest potential for dietary modulation to support endothelial function and BP regulation. Full article

The current work is driven by applying circular principles, and it investigated the potential recyclability of polybutylene succinate (PBS) containing brewer’s spent grain filler (BSGF, 30 wt%) in comparison to the recyclability of pure PBS. PBS is much more stable than the PBS/BSGF composite during processing cycles. Typically, thermomechanical degradation induces radical formation and branching of the macromolecular chain in PBS. Furthermore, PBS becomes less hydrophilic (by 53%, reaching 84°, approaching the 90° threshold), and its surface roughness increases by about 38% after five processing cycles. BSGF increases the viscosity of the melt, especially at low frequencies, and stabilizes the melt in the PBS/BSGF, which has lower torque variations during processing compared to pure PBS. Furthermore, BSGF in r-PBS/BSGF increases both hydrophilicity (by about 15%, from 75° to 64°) and surface roughness (by about 17%) after five processing cycles of the solid bio-composite and limits the formation of carboxylic groups during thermomechanical degradation. PBS is recyclable five times because it maintains its properties unchanged during extrusion cycles. At least two reprocessing steps are required for PBS/BSGF to obtain an optimal dispersion of BSGF, which can be re-extruded approximately three times. PBS/BSGF after four and five extrusion steps shows increased rigidity (E_t PBS/BSGF > E_t PBS) and reduced ductility (ε_b PBS/BSGF < ε_bt PBS), which could limit the recyclability of the PBS-based composite. Full article

In this work, a new asymmetric amidine–imine ligand, using 1,8-diaminonaphthalene as a rigid platform, was synthesized and characterized, and its ability to form complexes with aluminum(III) was investigated. Several aluminum complexes were synthesized and characterized in solution and in the solid state. The synthesis of a dihalogenated aluminum(III) complex (AlI₂L) using a reducing agent revealed an atypical pathway, which was investigated using Density Functional Theory (DFT). The dimethylated aluminum complex AlMe₂L and the dihalogenated aluminum complex AlI₂L were evaluated as catalysts for the transformation of CO₂ and epoxides into cyclic carbonates in the presence of Bu₄NI as a co-catalyst or in a single-component system, respectively. AlMe₂L/Bu₄NI appeared to be the most efficient system under 1 bar of CO₂ at 90 °C. Full article

We report here an in-depth study concerning the synthesis, NMR, and X-ray structure determination of two new polymorphs of 2-chloro-3′,4′-diacetoxy-acetophenone. A new, ecologically friendly method of synthesis in the solid phase, as well as a suitable method for protecting hydroxyl functionality, is presented. The ¹H- and ¹³C-NMR spectra as well as the single crystal X-ray diffraction studies proved unambiguously the structure of the compounds: the two polymorphs of 2-chloro-3′,4′-diacetoxy-acetophenone and 2-chloro-3′-hydroxy-4′-acetoxy-acetophenone. The polymorph I crystalizes in the monoclinic P21/c space group, while polymorph II crystalizes in the Sohnke P212121 space group of the orthorhombic system, with no interstitial solvate molecules. Significant differences were observed in the supramolecular interactions in the crystal structure of the two polymorphs. Polymorph I is characterized as a parallel packing of weakly interacting supramolecular layers oriented in the 1 1 0 plane. The crystal structure of polymorph II is much more complex: each molecule is interconnected through 12 (twelve) hydrogen bonds with 9 (nine) adjacent symmetry-related molecules. The monoacetoxy derivative 2-chloro-3′-hydroxy-4′-acetoxy-acetophenone 3 crystallizes in the monoclinic P2₁/c space group, with one molecule in the asymmetric unit. Full article

Asymmetric nanomotors are a class of self-propelled nanoparticles that exhibit asymmetries in shape, composition, or surface properties. Their unique asymmetry, combined with nanoscale dimensions, endows them with significant potential in environmental and biomedical fields. For instance, glutathione (GSH) induced chemotactic nanomotors can respond to the overexpressed glutathione gradient in the tumor microenvironment to achieve autonomous chemotactic movement, thereby enhancing deep tumor penetration and drug delivery for efficient induction of ferroptosis in cancer cells. Moreover, self-assembled spearhead-like silica nanomotors reduce fluidic resistance owing to their streamlined architecture, enabling ultra-efficient catalytic degradation of lipid substrates via high loading of lipase. This review focuses on three core areas of asymmetric nanomotors: scalable fabrication (covering synthetic methods such as template-assisted synthesis, physical vapor deposition, and Pickering emulsion self-assembly), propulsion mechanisms (chemical/photo/biocatalytic, ultrasound propelled, and multimodal driving), and functional applications (environmental remediation, targeted biomedicine, and microelectronic repair). Representative nanomotors were reviewed through the framework of structure–activity relationship. By systematically analyzing the intrinsic correlations between structural asymmetry, energy conversion efficiency, and ultimate functional efficacy, this framework provides critical guidance for understanding and designing high-performance asymmetric nanomotors. Despite notable progress, the prevailing challenges primarily reside in the biocompatibility limitations of metallic catalysts, insufficient navigation stability within dynamic physiological environments, and the inherent trade-off between propulsion efficiency and biocompatibility. Future efforts will address these issues through interdisciplinary synthesis strategies. Full article

Layered intercalating V₂O₅ (vanadium pentoxide) is a durable battery-type electrode material exploited in supercapacitors. The advancement of V₂O₅ nanomaterials synthesized from non-aqueous organic solvents holds significant potential for energy storage applications. Liquid-phase synthesis of orthorhombic V₂O₅ cathode material corroborated its compatibility with quartet glycols and allowed examination of their explicit roles in faradic charge storage efficacy. V₂O₅ was found to be an intercalative material in all the quartet glycols. The crystalline, rod-like morphology and monodisperse V₂O₅ electrode were ascribed to the effects of ethylene, diethylene, triethylene, and tetraethylene glycols. Notable differences were observed in the electrochemical analysis of the prepared V₂O₅ (EV, DV, TV, and TTV). In a three-electrode cell setup, the DV electrode demonstrated a superior specific capacity of 460.2 C/g at a current density of 1 A/g. From the Trasatti analysis, the DV electrode exhibited 961.53 C/g of total capacitance, comprising a diffusion-controlled contribution of 898.19 C/g and a surface-controlled contribution of 63.34 C/g. The aqueous asymmetric device DV//AC exhibited a maximum energy density of 65.72 Wh/kg at a power density of 1199.97 W/kg. The glycol-derived electrodes were anticipated to bepromising materials for supercapacitors and have the potential to meet electrochemical energy needs. Full article

The rational design of high-performance microwave absorbers with broadband coverage, superior attenuation, and environmental durability is critical for addressing challenges in both defense and civilian technologies. High-entropy alloys (HEAs) exhibit atomic-scale asymmetric arrangements, demonstrating exceptional potential for microwave absorption through their unique lattice distortion, high entropy, sluggish diffusion, and “cocktail effect”. This critical review article provides an overview of the progress made in the development and understanding of HEA-based microwave absorbing materials. Initially, the microwave dissipation mechanisms for HEAs were analyzed, where atomic-scale distortions enhance polarization loss and broaden resonance bandwidth. Subsequently, key synthesis techniques like mechanical alloying and carbothermal shock are discussed, highlighting non-equilibrium processing for phase engineering. Building on these foundations, the discussion then progresses to evaluate four principal material design approaches: (1) compositionally-tuned powders, (2) multifunctional core–shell structures, (3) phase-controlled architectures, and (4) two-dimensional/porous configurations, each demonstrating distinct performance advantages. Finally, the discussion concludes by addressing current challenges in quantitative property modeling and industrial scalability while outlining future directions, including machine learning-assisted design and flexible integration, providing comprehensive guidance for developing next-generation high-performance microwave absorbing materials. Full article

Asymmetric synthesis of chiral hydroxysulfones, key pharmaceutical intermediates, is challenging. We report an efficient synthesis from readily available materials via a one-pot photo-biocatalytic cascade reaction in aqueous conditions, utilizing visible light as an energy source. This sustainable process achieves up to 84% yields and 99% ee. Engineered ketoreductase produces R-configured products with high conversion and enantioselectivity across diverse substrates. Molecular dynamics (MD) simulations explored enzyme–substrate interactions and their influence on reaction activity and stereoselectivity. Full article

The regio- and stereoselective adjacent bifunctionalization of olefins with amine and halogen groups can be effectively accomplished through catalytic haloamination methods. Stereoselective haloamination has emerged as a pivotal methodology for the introduction of halogen functional groups into chiral amines, demonstrating substantial applications in medicinal chemistry and organic synthesis. Since 1999, significant advancements have been achieved in this field, driven by innovations in catalytic systems and methodologies. The stereoselective haloamination of both functionalized and nonfunctionalized alkenes employing chiral catalysts has emerged as a prominent area of research. This review provides a comprehensive overview of the research progress in stereoselective haloamination reactions from 1999 to 2023. It examines the innovations in catalyst design that have facilitated more efficient and selective transformations. The review also analyzes the optimization of reaction conditions, which has been crucial in improving the overall performance and applicability of these reactions. Furthermore, it explores the diverse range of haloamination reactions that have been developed, emphasizing their potential for the synthesis of complex and valuable chemical structures. Additionally, this review offers insightful perspectives on future research directions in stereoselective haloamination reactions. Full article

Rye regeneration in anther cultures is problematic and affected by albino plants. DNA methylation changes linked to Cu²⁺ ions in the induction medium affect reprogramming microspores from gametophytic to sporophytic path. Alternations in S-adenosyl-L-methionine (SAM), glutathione (GSH), or β-glucans and changes in DNA methylation in regenerants obtained under different in vitro culture conditions suggest a crucial role of biochemical pathways. Thus, understanding epigenetic and biochemical changes arising from the action of Cu²⁺ and Zn²⁺ that participate in enzymatic complexes may stimulate progress in rye doubled haploid plant regeneration. The Methylation-Sensitive Amplified Fragment Length Polymorphism approach was implemented to identify markers related to DNA methylation and sequence changes following the quantification of variation types, including symmetric and asymmetric sequence contexts. Reverse-Phase High-Pressure Liquid Chromatography (RP-HPLC) connected with mass spectrometry was utilized to determine SAM, GSH, and glutathione disulfide, as well as phytohormones, and RP-HPLC with a fluorescence detector to study polyamines changes originating in rye regenerants due to Cu²⁺ or Zn²⁺ presence in the induction medium. Multivariate and regression analysis revealed that regenerants derived from two lines treated with Cu²⁺ and those treated with Zn²⁺ formed distinct groups based on DNA sequence and methylation markers. Zn²⁺ treated and control samples formed separate groups. Also, Cu²⁺ discriminated between controls and treated samples, but the separation was less apparent. Principal coordinate analysis explained 85% of the total variance based on sequence variation and 69% of the variance based on DNA methylation changes. Significant differences in DNA methylation characteristics were confirmed, with demethylation in the CG context explaining up to 89% of the variance across genotypes. Biochemical profiles also demonstrated differences between controls and treated samples. The changes had different effects on green and albino plant regeneration efficiency, with cadaverine (Cad) and SAM affecting regeneration parameters the most. Analyses of the enzymes depend on the Cu²⁺ or Zn²⁺ ions and are implemented in the synthesis of Cad, or SAM, which showed that some of them could be candidates for genome editing. Alternatively, manipulating SAM, GSH, and Cad may improve green plant regeneration efficiency in rye. Full article