The emergence of collaborative robotics and additive manufacturing of equipment consumables has had a significant impact on the development of chemical synthesis, biomedicine, the food industry, and agriculture. However, high cost hampers the application of collaborative robots in organic and physical chemistry. Here we suggest a low-cost 3D-printed robotic platform made from gripper and dispenser manipulators coupled with computer vision tools that provide full automation of the Knoevenagel reaction of barbituric acid with aromatic aldehydes, ranging from mixing of reagents to kinetic spectrophotometric monitoring. Screening of conditions of the Knoevenagel reaction between barbituric acid and aromatic aldehydes (reagent ratio, concentration and type of polyelectrolytes and interpolyelectrolyte complexes, as well as type of aromatic aldehyde) powered by the developed open-source Python-based software boosts the discovery of optimal conditions for enhanced reaction kinetics. Our robotic system performs dataset collection and discovers smart polyelectrolyte coacervate catalysis.

Supramolecular aggregates constructed through multiple noncovalent interactions have garnered significant attention across various fields due to their modular and controllable assembly methods. In this study, we introduce a novel approach to modulate the hydrophilicity and hydrophobicity of supramolecular systems by incorporating structurally diverse molecules through hexahydrogen bonding interactions in a polar solvent. To investigate the synergistic effects of host-guest interactions and hydrogen bonding on the formation of supramolecular aggregates, molecules of Hamilton wedge-functionalized pillar[5]arene (H1), barbituric acid derivatives with hydrophilic or hydrophobic chains (C1-2), and a guest molecule (G) featuring a tetraphenylethylene (TPE) core were designed and synthesized. Two types of supramolecular aggregates, H1C1G and H1C2G, were constructed via orthogonal two-step assembly, resulting in a diverse range of molecular aggregate morphologies in both nonpolar and polar solvents. Ordered nanosheets and vesicle structures were displayed by aggregate H1C1G with a hydrophobic chain and aggregate H1C2G with a hydrophilic chain, through hydrophilic/hydrophobic and π-π stacking interactions. Interestingly, toxic environmental pollutants such as succinonitrile, hexanedinitrile, and methylviologen were effectively detected by fluorescent probe H1C1G with high sensitivity and selectivity. Furthermore, the coassemblies of H1C2G and Nile red exhibit FRET effects and are sensitive to acid, enabling acid-sensitive information encryption. The findings of this study offer new insights into the facile construction of functionalized supramolecular aggregates with various morphologies for practical applications of supramolecular soft materials.

ABSTRACT Cervical cancer is a distinct form of cancer that impacts women globally, with an annual occurrence of 604 thousand new cases and 341 thousand deaths. The current chemo‐therapeutic treatment is limited by drug resistance and concerns about toxicity, highlighting the need for new potent, nontoxic, and cost‐effective alternatives. In this work, we synthesized a series of barbituric acid–derived azo dye ligands ( L1 – L4 ). All four ligands were confirmed by FTIR and NMR spectroscopy. Among them, L1 forms a stable dinuclear Cu (II) complex ( B1 ), which was comprehensively characterized by UV–Vis, FTIR, SC‐XRD, EPR, TGA, and XPS. Azo groups (‐N=N‐) are reactive organic groups that interact with biomolecules like proteins and nucleic acids to contribute to the biological activity of azo substances. B1 exhibits a GI50 value of 10 μM, indicating significant anticancer potential. It also shows inhibitory properties against bacteria and fungi, suggesting potential antimicrobial impact. Hence, this current study emphasizes the anticancer and antimicrobial capabilities of the synthesized complex. Moreover, the sensitivity of B1 to fluoride ions suggests its capacity to function as a sensor. The remarkable biological activity and sensitivity of B1 indicate its potential for therapeutic and diagnostic purposes, especially in targeting resilient microbial strains, cancer cells (HeLa), and environmental screening.

A novel 4-chloro-2,5-dioxo-6-phenyl-5,6-dihydro-2H-pyrano[3,2-c]quinoline-3-carbaldehyde was synthesized via the Vilsmeier reaction and served as a key intermediate for constructing a series of heterocyclic quinoline derivatives. Modification of the pyranoquinoline-3-carbaldehyde scaffold through subsequent reactions with hydrazines, o-phenylenediamine, and barbituric acid led to quinoline derivatives bearing pyrazole, diazepine, and pyrimidine moieties. These structural variations significantly influenced the compounds’ biological profiles. Spectroscopic techniques and elemental analysis were used to confirm the structures. Favorable binding affinities were demonstrated by molecular docking tests against human thymidylate synthase (HT-hTS, PDB: 6QXG), with docking scores (−8.4 to −10.7 kcal/mol) higher than those of the reference ligand 5-fluorodeoxyuridinemonophosphate FdUMP (−7.8 kcal/mol). Cytotoxicity was evaluated against HepG-2 and HCT-116 cell lines using the MTT assay. Compound 14 showed the most potent antiproliferative activity, with IC50 values of 33.61 µM (HepG-2) and 50.73 µM (HCT-116), comparable to that of 5-fluorouracil (5-FL). These results highlight quinoline derivatives as promising anticancer agents and HT-hTS inhibitors.

Abstract In this study, nanotubular carbon nitride (CN) was successfully synthesized via a supramolecular self‐assembly method using varied molar ratios of melamine (MA) to barbituric acid (BA). The resulting supported Pd catalysts demonstrated exceptional catalytic activity for hydrogen production through formic acid dehydrogenation, achieving an initial turnover frequency (TOF) of 1920.4 h −1 at 348 K. By systematically adjusting the MA:BA molar ratio, hydrothermal temperature, and reaction time, the chemical structure, morphology, and the type/content of nitrogen‐containing species in CN were tailored. Notably, the nature and distribution of nitrogen‐containing functional groups in nanotubular CN significantly modulated the electronic properties of Pd, thereby affecting the catalytic performance. The remarkable activity originated from the synergistic effect of Pd and pyrrolic N interactions, coupled with the small particle size and high dispersion of Pd nanoparticles.

Effect of barbituric acid in regulating the Al anode/electrolyte interface layer for Al-air batteries in alkaline medium

Hepatitis B Virus (HBV) continues to pose a significant global health challenge, with over 254 million chronic infections and current therapies being non-curative, necessitating lifelong treatment. The HBV ribonuclease H (RNase H) is essential during HBV reverse transcription by cleaving the viral pregenomic RNA after it has been copied into the (−) polarity DNA strand, enabling the viral polymerase to synthesize the (+) DNA strand. Although RNase H inhibition terminates viral replication and thus viral infectiveness, its targeting as an HBV treatment is unexploited. Its catalytic site contains four carboxylates that bind to two Mg2+ ions essential for RNA hydrolysis. As part of our ongoing research on RNase H inhibitors, we developed 23 novel N-hydroxypyridinedione (HPD) analogues. Specifically, 17 HPD imines, 4 HPD oximes, 1 2,6-diamino-4-((substituted)oxy)pyrimidine 1-oxide derivative, and 1 barbituric acid analogue were designed, synthesized, and tested for their anti-HBV activity. The HPD derivatives could be docked in the RNase H active site to coordinate the two Mg2+ ions and effectively inhibited viral replication in cellular assays. The 50% effective concentration (EC50) values of these HPD compounds ranged from 0.5 to 73 μM, while the 50% cytotoxic concentration (CC50) values ranged from 15 to 100 μM, resulting in selectivity indexes (SIs) up to 112. Furthermore, the novel HPD derivatives exhibited favourable pharmacokinetic-relevant characteristics, including high cellular permeability, good aqueous solubility, and overall drug-like properties. These findings indicate that HPD imines and oximes possess substantial antiviral potency and selectivity against HBV, underscoring the potential of the HPD scaffold as a promising framework for the development of next-generation anti-HBV agents.

An unprecedented organocatalytic enantioselective methodology has been unlocked to access oxindole-fused spiro[furo[2,3-d]pyrimidines] with high bond efficiency (two new C-C bonds and one C-O bond) and two contiguous stereocenters via Cascade Michael-Cyclopropanation-Rearrangement. A series of spiro[furo[2,3-d]pyrimidines] has been synthesized in excellent yield (up to 90%) and stereoselectivity (dr up to 99:1, er up to 97:3) from 3-chlorooxindoles and 5-alkylidene barbituric acids at room temperature. 1H NMR and HRMS studies have been conducted to define the reaction pathway.

A new natural deep eutectic solvent (DES) based on arginine (ARG) and glutaric acid (GLU) was prepared. The eutectic point phase diagram showed that the best ratio for preparation of ARG/GLU-DES is one mole of ARG to three moles of GLU. Then, the new DES was characterized by eutectic points, FT-IR, 1H NMR, TGA/DTA, and densitometry techniques. Additionally, it was demonstrated to be an effective catalyst for the green synthesis of pyrano[2,3-d]-pyrimidines through a one-pot three-component condensation reaction of aromatic aldehydes, barbituric acid, and 4-hydroxycoumarin at 80 °C under solvent-free conditions with high yields and short reaction times.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-19681-5.

Trypsin is a serine protease enzyme that has a wide range of functions in physiological and pathological processes. Although most of its functions are often associated with positive effects, there is still a need for its inhibition, because its overexpression has been associated with various forms of cancers and poses to be fatal if left unaddressed. Early detection of elevated trypsin levels can help diagnose cancer, and its inhibition can prevent its progression. Therefore, Molecular Docking was performed for four compounds, allantoin, barbituric acid, azoindole, and trilobatin, to test their inhibition potential against human trypsin. The binding affinities and the interacting residues were predicted using AutoDock. Azoindole, out of the four compounds, showed the highest binding affinity, followed by trilobatin. Moreover, the trypsin inhibition assay was performed using trilobatin as the inhibitor. A constant concentration of trypsin was maintained at 0.013mg/mL. To assess the use of trilobatin as a drug, SwissADME was employed. Its use as a potential oral drug was discovered.

Abstract This study presents a sustainable and efficient visible‐light‐driven organophotocatalytic strategy for transforming the methylene carbon of barbituric acids into valuable hydrazones and spirocyclic products. The reaction proceeds smoothly under mild conditions by utilizing eosin Y as a green photocatalyst and atmospheric oxygen as the sole oxidant. This method provides an environmentally friendly alternative to traditional approaches and offers intriguing mechanistic insights into umpolung C(sp3)‐H functionalization, thereby paving the way for novel reactivity in barbiturate chemistry.

Synthesis, Characterization, Electrochemical Sensing, DFT Analysis, Molecular Docking and Anticancer Activity of a Novel Thiadiazole-Based Azo Dye Incorporating a Barbituric Acid Scaffold

Development of novel coumarin-barbituric acid hybrids as a new class of anti-breast cancer agents.

Abstract This research describes a synthesis method using Fe3O4@SiO2@APIDSO3H as a magnetic nanocatalyst for preparing α‐substituted phosphonates by domino‐Knoevenagel–phospha‐Michael reaction. The reaction involves 1,3‐dicarbonyl compounds (dimedone and 1,3‐dimethyl barbituric acid) reacting with different aromatic aldehydes and triethyl phosphite. The Fe3O4@SiO2@APIDSO3H catalyst was previously prepared and characterized. The synthesized products were identified using 1H‐NMR, 13C‐NMR, 31P‐NMR, FT‐IR spectroscopy, and CHNS analysis. The resulting compounds possess reactive functional groups in their structure, making them suitable as building blocks for further chemical modifications in medicinal and biochemical applications. This approach also offers advantages like catalyst recovery and reusability, short reaction times, and simplified workup procedures.

The work investigated the features of the formation and properties of monolayer films of sulfur-containing molecules of inorganic and organic origin on the gold surface of the SE SPR sensor for surface protection, stabilization of the properties of the metal film, and its adaptation to the adsorption of biological molecules. The process of forming a reactively inert coating (gold sulfide – AuxSy) for non-destructive physical adsorption of biomolecules onto the surface of a gold film was studied. It was shown (based on resonant SPR curves and the specific reaction of soybean trypsin inhibitor (SIT) – enzyme trypsin (Tp)) that under the action of reactive annealing of a polycrystalline gold film in a hydrogen sulfide (H2S) atmosphere for 15 hours, a dense monolayer of AuxSy is formed. The formation process is accompanied by the reconstruction of the gold surface, which stabilizes the characteristics of the SPR transducer and creates a boundary with less surface roughness and non-destructive properties for the physical adsorption of biologically active molecules. The feasibility of using organic films of dodecanethiol HS(CH2)11CH3, obtained by the method of self-organization of molecular (SOM) ensembles from solution, for protecting the working surface of the sensor, stabilizing the properties of the metal film, and adapting it to the adsorption of biological molecules is shown. In order to increase the speed of molecular binding, as well as the amplitude of the sensor response by increasing the area of the sensitive surface, a method of oriented fixation of receptor molecules in their natural, in a state undeformed by interaction with the metal inside the three-dimensional structure of the polysaccharide hydrogel – dextran, which was fixed on the gold surface using a thiol layer. The method of layer-by-layer deposition from aqueous solutions was used to form an inorganic five-layer film of copper (II) aminopentacyanoferrate (Cu3[Fe(CN)5NH3]2) on a COM-derived gold surface for the purpose of oriented immobilization of antibodies against human fibrinogen. It has been demonstrated that the use of this modification increases the response to the presence of fibrinogen in the sample by almost twofold. Another idea for using organic molecules called mercaptans, sulfur-containing molecules of various lengths and structures, was to create selective binding conditions for selected molecules using the molecular imprinting method. A method for forming an organic monolayer matrix on the surface of a gold film for molecular recognition of not very large molecules of barbituric acid C4H4O3N2 has been proposed and implemented. The matrix was obtained by the method of random co-adsorption of a mixture of dodecanethiol HS(CH2)11CH3 and thiobarbituric acid C4H4O2N2S from solution. It is shown that the mechanism that determines the selectivity of the interaction is the formation of fingerprints of analyte molecules in the surface organic layer, which allows the detection of barbituric acid against the background of its chemical analogue - veronal C8H12O3N2. To form a defect-free nanomolecular architecture of a self-organized coating on the surface of the CE sensors of the SPR, a low-temperature annealing technology (120 °C for 30 minutes) is proposed, which leads to smoothing of the small-scale relief of the gold surface and obtaining optimal parameters of the resonance curve.

An in-situ CO₂-assisted dispersive micro solid phase extraction was developed using a covalent organic framework synthesized from melamine and barbituric acid as a sorbent for the extraction of Cd(II) and Zn(II) ions from honey samples. The structural and morphological characteristics of the sorbent were evaluated using scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectrometry. The CO₂ generated by reacting tartaric acid and sodium hydrogen carbonate enabled rapid dispersion of the sorbent within the sample solution, ensuring optimal contact with the target ions. After adsorption, the dispersed sorbent particles were separated via centrifugation, followed by elution with diluted nitric acid solution to retrieve the extracted heavy metals from the sorbent surface. The analytes collected in the eluate were quantified via flame atomic absorption spectrometry. Key experimental parameters, including tartaric acid and sodium bicarbonate amounts, sorbent dosage, type and volume of elution solvent, temperature, salt addition, pH, complexing agent concentration, and centrifugation conditions were systematically optimized. The method demonstrated high sensitivity, with the limits of detection of 0.17 and 0.092 µg L− 1 and broad linear range spanning 0.5–100 and 0.25–100 µg L− 1 for Cd(II) and Zn(II) ions, respectively. Extraction recoveries of 97.2 and 95.5%, with relative standard deviations of 3.6 and 2.7% for Cd(II) and Zn(II) ions, respectively, were obtained. Validation using a certified reference material confirmed the method’s accuracy, and application of the method on honey samples demonstrated its practicality.

Piezochromic behavior of orange fluorescent flexible crystals based on barbituric acid derivative

Acylhydrazone derivatives of barbituric acid: Synthesis, in vitro α-amylase inhibition, molecular docking, ADMET and DFT analysis

Abstract: A straightforward and facile method for the synthesis of imidazo[1,2-a]pyridine derivatives by one-pot, three-component reaction of phenyl glyoxals, 2-aminopyridines, and barbituric acids has been developed. The synthesis was performed in a microwave reactor and under solvent-free conditions without using any catalyst. The synthesis displayed many other attractive features such as high efficiency, short reaction time, simple product purification, and environmentally benign reaction conditions. Moreover, the synthesis could be applied on a gram scale without any significant decrease in reaction yield. Eleven imidazo[1,2-a]pyridine adducts were provided in high yields (82-96%), and their structures were confirmed by NMR data. A comparison between this method and the literature report was also included. A plausible reaction mechanism involving a Knoevenagel condensation and aza-Michael addition was also suggested. other: None

Background: Prostate cancer (PCa) is the primary contributor to male cancer-related mortality and currently lacks effective treatment options. The Modified Guizhi Fuling Decoction (MGFD) is used in clinical practice to treat multiple tumors. This research focused on the mechanisms of action (MOA) in MGFD that inhibit PCa. Methods: The impact of MGFD on PCa cells (PC3 and DU145) was examined via Cell Counting Kit-8, wound healing assays, and transwell assays. To determine the MOA, high-throughput sequencing based high-throughput screening (HTS2) was utilized along with network pharmacology. Results: The findings indicated that MGFD suppressed the proliferation, migration, and invasion of PCa cells. We then utilized the HTS2 assay to generate 270 gene expression profiles from PCa cells perturbed by MGFD. Large-scale transcriptional analysis highlighted three pathways closely associated with PCa: the TNF signaling pathway, cellular senescence, and FoxO signaling pathway. Through the combination of network pharmacology and bioinformatics, we discovered four primary targets through which MGFD acts on PCa: AKT serine/threonine kinase 1 (AKT1), Caspase-8 (CASP8), Cyclin-Dependent Kinase 1 (CDK1), and Cyclin D1 (CCND1). Finally, molecular docking demonstrated that the potential bioactive compounds baicalein, quercetin, and 5-[[5-(4-methoxyphenyl)-2-furyl] methylene] barbituric acid strongly bind to CDK1, AKT1, and CASP8, respectively. Conclusions: This research shows that MGFD displays encouraging anticancer effects via various mechanisms. Its multi-target activity profile underscores its promise as a potential therapeutic option for PCa treatment and encourages additional in vivo validation studies.