Strong Binding Energy Research Articles

Spatial Confinement Effect of Mineral‐Based Colloid Electrolyte Enables Stable Interface Reaction for Aqueous Zinc–Manganese Batteries

AbstractThe rational design of inorganic colloid electrolytes enables the manipulation of the solvation structure of Zn2+ ions and addresses zinc dendrite formation and manganese dissolution in aqueous zinc–manganese batteries. In this study, magnesium aluminosilicate (MAS) powder is used to fabricate a mineral‐based colloid electrolyte for Zn//α‐MnO2 batteries. According to theoretical calculations, MAS has a stronger binding energy with Zn2+/Mn2+ ions than with H2O molecules, suggesting the possibility of regulating the solvation structure of Zn2+/Mn2+ ions in a MAS–colloid electrolyte. Based on the experimental results, a high ionic conductivity, wide operating voltage, low activation energy barrier, and stable pH environment is achieved in the MAS–colloid electrolyte. As expected, long‐term cyclic stability can be maintained for 3500 h at 0.2 mA cm−2 in Zn//Zn cells, and high capacities of 255.5 and 239.8 mAh g−1 are retained at 0.2 and 0.5 A g−1 after 100 cycles in Zn//α‐MnO2 batteries, respectively. This performance is attributed to the spatial confinement effect of MAS on the active H2O molecules, which effectively reshapes the solvation structure of Zn2+ ions, guaranteeing reversible zinc deposition, suppressing active manganese dissolution, and ensuring stable interfacial reactions. This work will drive the development of mineral‐based electrolytes in zinc‐based batteries.

DFT investigation of Co/Ni decorated borophene for efficient removal of methylene blue from wastewater effluent

Removal of dyes is a significant aspect of environmental remediation to ensure clean water and atmosphere. In this study, we report metals decorated (M = Co, Ni) borophene (B36) for effective removal of cationic dye (methylene blue) using density functional theory calculations. The calculations shows that the metals are strongly anchored at the surface of B36 system with stronger binding energies and larger positive charge. The molecular dynamics simulations evince that the M@B36 are thermally stable and withstand to high temperature as 500 K. The application of M@B36 as adsorbent for the removal of MB dye shows that the dye could strongly adsorbed over the M@B36 surface involving the formation of a chemical bond and larger adsorption energies (−2.99 and −2.73 eV for MB@Co-B36 and −2.27 and −2.11 eV for MB@Ni-B36) compared to bare B36 system. The electron density difference, partial density of states and atom in molecule analysis gives evidences of the presence of stronger covalent bonds between the M@B36 and MB. This chemical bonding leads to the chemisorption of MB over the M@B36 surface. The solvation effect decreases the desorption time of the MB molecules from M@B36. This is further verified by explicit solvent effects, which shows that the addition of water molecules weaker the intermolecular forces and lower the adsorption energy value to −1.32 eV. The protonated dye molecule is strongly adsorbed over the metal-decorated B36 system, showing that the dye molecule adsorption in an acidic medium is feasible. The selectivity study shows that the MB dye is selectively adsorbed over the metal-decorated borophene compared to water molecules due to larger adsorption energy values. These results show that this study will help the experimentalists to explore M@B36 system as new metal doped adsorbent for removal of toxic pollutants from waste water.

Discovery of novel azo pyrimidinone derivatives as B-cell lymphoma-2 inhibitors with potential antineoplastic activity: Synthesis, characterization, in-silico, and in-vitro studies

In the present investigation, novel azo compounds containing pyrimidinone moiety incorporated with different heterocycles were synthesized and characterized using spectroscopic techniques including FT-IR, 1H-NMR, 13C-NMR, and elemental analysis. These azo derivatives were assessed in- silico to determine how well they could inhibit the antiapoptotic B-cell lymphoma-2 (Bcl-2) protein while providing information about their pharmacokinetic characteristics. Our results elucidated that the majority of these new compounds demonstrated moderate to strong binding energies against Bcl-2 target protein comparable to that of venetoclax FDA-approved Bcl-2 inhibitor. Compound 4 showed the top-ranked binding energy followed by compound 5 and compound 3 with values equal to -11.65, -9.53, and -7.82 kcal/mol respectively, while compounds 6 and 7 showed moderate binding energies compared with venetoclax drug that give binding energy equal to -6.95 kcal/mol Furthermore, the in-vitro investigations observed that compounds 4, 5 and 3 demonstrated superior anticancer efficacy against HepG2 and MCF-7 compared to venetoclax drug that gives IC50 equal to 5.10±0.54 and 4.17±0.8 μM respectively. Moreover, all newly synthesized compounds had no cytotoxic impact on WI-38 normal cells contrary to venetoclax drug (26.72±0.94 μM) which was confirmed also through ADMES drug-likeness scores study. Additionally, compounds 4, 5, and 3 revealed an efficient antioxidant scavenging capacity towards DPPH free radicals while compounds 6 and 7 showed a weak scavenging effect compared with standard L. ascorbic acid. Ultimately, the newly synthesized pyrimidinone compounds 4, 5, and 3 that were examined showed encouraging apoptotic and antiproliferative properties. Further, in upcoming clinical studies, the newly synthesized pyrimidinone compounds may prove to be effective anticancer medicines.

Screening of Optimal Phytoconstituents through in silico Docking, Toxicity, Pharmacokinetic, and Molecular Dynamics Approach for Fighting against Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome (PCOS) is a hormonal disorder caused by excessive secretion of male sex hormones in females. Herbal remedies for PCOS are lightning up as they bypass the adverse effects and are profoundly safe on prolonged usage. The present study included a selection of 34 herbs pursuing biological effects on the uterus, and their major chemical constituents were subjected to a series of in silico techniques using different software. The proteins contributing majorly to the hormonal functions like Human cytochrome P450 CYP17A1 (3RUK), Progesterone (1E3K), and estrogen receptor (1X7R) were selected for the study. Molecular docking studies were performed using AutoDock 1.5.7. The pharmacokinetic properties were predicted using the SwissADME online tool, while toxicity parameters were assessed with OSIRIS toxicity explorer and pkCSM. Molecular dynamics simulations and free energy calculations were performed using the Schrödinger suite. Constituents with a basic steroidal nucleus demonstrated high binding energy values. An analysis of all the in silico techniques showed that Sarsasapogenin from Asparagus racemosus exhibited strong binding energies of -10.88 kcal/mol, -10.51 kcal/mol, and -9.79 kcal/mol with the selected specific proteins. In molecular dynamics simulations, Sarsasapogenin displayed ideal stability, with RMSD fluctuations below 3 Å and RMSF slightly higher than the corresponding peak of apoprotein. Additionally, it showed a favorable druglikeness profile and non-toxic effects across all screened parameters. From the list of the selected constituents, sarsasapogenin was found to be ideal, and further research on it for targeting PCOS is expected to yield promising results.

Evaluation of the Mechanism of Yishan Formula in Treating Breast Cancer Based on Network Pharmacology and Experimental Verification.

Yishan formula (YSF) has a significant effect on the treatment of breast cancer, which can improve the quality of life and prolong the survival of patients with breast cancer; however, its mechanism of action is unknown. In this study, network pharmacology and molecular docking methods have been used to explore the potential pharmacological effects of the YSF, and the predicted targets have been validated by in vitro experiments. Active components and targets of the YSF were obtained from the TCMSP and Swiss target prediction website. Four databases, namely GeneCards, OMIM, TTD, and DisGeNET, were used to search for disease targets. The Cytoscape v3.9.0 software was utilized to draw the network of drug-component-target and selected core targets. DAVID database was used to analyze the biological functions and pathways of key targets. Finally, molecular docking and in vitro experiments have been used to verify the hub genes. Through data collection from the database, 157 active components and 618 genes implicated in breast cancer were obtained and treated using the YSF. After screening, the main active components (kaempferol, quercetin, isorhamnetin, dinatin, luteolin, and tamarixetin) and key genes (AKT1, TP53, TNF, IL6, EGFR, SRC, VEGFA, STAT3, MAPK3, and JUN) were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the YSF could affect the progression of breast cancer by regulating biological processes, such as signal transduction, cell proliferation and apoptosis, protein phosphorylation, as well as PI3K-Akt, Rap1, MAPK, FOXO, HIF-1, and other related signaling pathways. Molecular docking suggested that IL6 with isorhamnetin, MAPK3 with kaempferol, and EGFR with luteolin have strong binding energy. The experiment further verified that YSF can control the development of breast cancer by inhibiting the expression of the hub genes. This study showed that resistance to breast cancer may be achieved by the synergy of multiple active components, target genes, and signal pathways, which can provide new avenues for breast cancer-targeted therapy.

DNA Nucleobase Interaction Driven Selective Sensing Properties of Monolayer Delta Tellurene

In this study, we investigate the interaction between DNA nucleobases and semiconducting monolayer delta tellurene (δ(Te)) using a DFT framework with a vdW functional. Our results suggest that nucleobases adhere to the monolayer through physisorption, with Cytosine having the highest binding energy per atom and Thymine the lowest. The selectivity of signal detection produced by each nucleobase using δ(Te) is larger for Thymine (22.27%). Guanine exhibits a longer resident time due to its stronger binding energy with the tellurene surface, while Thymine displays the shortest residence time. The semiconducting behavior of the nucleobase+ δ(Te) system is captured in an STM-like setup, with tunneling current peaking at +1.2 V. These findings, coupled with modulations in quantum capacitance pre- and post-DNA binding, suggest promising sensing applications. Guanine exhibits a red shift of 0.60 eV in the imaginary part of the dielectric function, while adenine shows a 0.30 eV red shift in electron energy loss (EEL) spectra. Our results demonstrate the potential of δ(Te) monolayers in fabricating sensors for DNA sequencing devices.

Liner-chain polysaccharide binders with strong chemisorption capability for iodine species enables shuttle-free zinc-iodine batteries

Designing functional binders is demonstrated an effective solution to address the serious issues of active iodine dissolution and polyiodide shuttle faced by aqueous zinc-iodine batteries (AZIBs). Herein, a series of linear-chain polysaccharides are systematacially investigated as the potential water-soluble binders for iodine-loading cathode of AZIBs. According to the results of spectral characterizations and theoretical calculations, SA binder, as the representative of polysaccharides, is verified with strong chemisorption capability and high binding energy for the iodine intermediates owing to the existence of active ether and carboxyl groups, which contributes to suppress the polyiodide shuttle and active iodine dissolution. Meanwhile, the lower Gibbs free energy values indicate the introduction of SA binder is conducive to boost the iodine redox reaction kinetics of iodine-loading cathode. Benefitting from these merits, the Zn//CAC@I2 batteries with SA biner delivers superior self-discharge resistance capability, excellent rate performance, and ultra-durable cycling stability with high reversible capacity of 105.2 mAh g−1 after 8000 cycles at 1 A g−1 and 86.3 mAh g−1 after 40,000 cycles at 5 A g−1, respectively. This work will enlighten the research and development of binder materials for advanced iodine-based energy storage devices, and facilitate the practical application of both polysaccharide binders and AZIBs.

Rationally Designed L12-Pt2RhFe Intermetallic Catalyst with High CO-Tolerance for Alkaline Methanol Electrooxidation.

It is a grand challenge to deep understanding of and precise control over functional sites for the rational design of highly efficient catalysts for methanol electrooxidation. Here, an L12-Pt2RhFe intermetallic catalyst with integrated functional components is demonstrated, which exhibits exceptional CO tolerance. The Pt2RhFe/C achieves a superior mass activity of 6.43 A mgPt -1, which is 2.23-fold and 3.53-fold higher than those of PtRu/C and Pt/C. Impressively, the Pt2RhFe/C exhibits a significant enhancement in durability owing to its high CO-tolerance and stability. Density functional theory calculations reveal that high performance of Pt2RhFe intermetallic catalyst arises from the synergistic effect: the strong OH binding energy (OHBE) at Fe sites induce stably adsorbed OH species and thus facilitate the dehydrogenation step of methanol via rapid hydrogen transfer, while moderate OHBE at Rh sites promote the formation of the transition state (Pt-CO···OH-Rh) with a low activation barrier for CO removal. This work provides new insights into the role of OH binding strength in the removal of CO species, which is beneficial for the rational design of highly efficient catalysts.

An Extensive Computational Investigation of Mycobacterium tuberculosis Pantothenate Synthetase Inhibitors from Diverse‐Lib Compounds Library

AbstractAntibiotics have played a crucial role in significantly reducing the incidence of tuberculosis (TB) infection worldwide. Even before the mid‐20th century, the mortality rate of TB onset within five years was around 50 %. So, the introduction of antibiotics has changed the scenario of TB from a serious threat to a manageable one. However, the emergence of resistance to anti‐TB drugs poses a significant challenge. So, to overcome this situation the therapeutic approaches and drug targets need to be reformed. This study focused on finding potential inhibitors by targeting Pantothenate Synthetase, a crucial enzyme for Mycobacterium tuberculosis (Mtb) survival, through computational drug discovery methods. Molecular docking and virtual screening were employed to identify potential inhibitors from Diverse‐lib. Four compounds, namely CID2813602, 24357538, CID753354, and CID4798023, exhibited strong binding energies and stable interaction with the target protein. Further assessment of these compounds through MD simulation and Post MD simulation showed significant dynamic stability. The minimum energy transition calculated using the free energy landscape analysis of these compounds when docked with Pantothenate Synthetase confirmed the stability of each complex due to its minimum energy production. The free binding energy calculation of each complex also showed the intramolecular interaction contributes to the strong binding affinity of the compounds within the enzyme's active site clarifying their mechanisms of action. This research showcases the effectiveness of computational methods in promptly identifying potential anti‐TB drugs, paving the way for future experimental validation and optimization. It holds promise for the development of new treatments targeting drug‐resistant TB strains.

Efficient CO2 Reduction Reaction on Cu-Decorated Biphenylene.

Developing efficient electrocatalysts for CO2 reduction into value-added products is crucial for a green economy. Inspired by the recent experimental synthesis of biphenylene (BPH) and the excellent catalytic activity of copper dispersed on two-dimensional (2D) materials, we chose to systematically investigate the pristine, defective, and Cu-decorated BPH for the electrocatalytic CO2 reduction to value-added hydrocarbons. It is observed that the CO2 molecules bind weakly to the pristine BPH, indicating their chemical inertness. Carbon single-vacancy defects facilitate CO2 adsorption with a strong binding energy (Eb) of -3.23 eV, detrimental to the CO2 reduction reaction (CRR) mechanism. We have further investigated the binding energy and kinetic stability of Cu-decorated BPH as a single-atom-catalyst (SAC). The molecular dynamics simulations confirm the kinetic stability, revealing that the Cu-atom avoids agglomeration under low metal dispersal conditions. The CO2 molecule gets adsorbed horizontally on the Cu-BPH surface with a ΔEb of -0.52 eV. The CRR mechanism is investigated using two pathways beginning with two different initial states, formate (*OCOH) and carboxylic (*COOH). The formate pathway confirms the conversion of *OCOH to *HCOOH with the rate-limiting potential (UL) of 0.39 eV for the production of HCOOH, while for the carboxylic pathway, the conversion of *COH to *CHOH has a UL of 0.32 eV, eventually producing CH3OH. Our findings highlight the role of Cu-BPH as an efficient SAC for CO2 catalytic activity to C1 products, as compared to the state-of-the-art Cu, and holds promise as an electrocatalyst for CRR.

Exploring the Antibacterial and Antibiofilm Efficacy of Psammogeton biternatum Edgew and Identification of a Novel Quinoline Alkaloid using X-ray Crystallography.

The prevalence of resistance to harmful human pathogens is steadily rising, emphasizing the urgent need to identify novel antimicrobial compounds. For this purpose, plants stand out as a significant source of bioactives worthy of exploration. Among these, alkaloids, a vast and structurally diverse category of plant secondary metabolites, have emerged as a foundation for crucial antibacterial medications such as metronidazole and the quinolones. In the current work, the crude methanol leaf extract of Psammogeton biternatum Edgew collected from District Bannu, Pakistan, was subjected to TLC (indirect) bioautography and X-ray crystallography for the isolation of potential antibacterial agents. From the crude extract, a novel quinoline alkaloid called quinoline dione ((3R,3aS,5aR)-3,5a,9-trimethyl-3a,4,5,5a-tetrahydro-2H-isoxazolo[2,3-a] quinoline-2,8(3H)-dione (C14H17NO3)) was isolated. The crystal information (M = 247.296 g/mol) is as follows: orthorhombic, P212121, a = 7.7339(14) Å, b = 10.7254(19) Å, c = 15.730(2) Å, V = 1304.8(4) Å3, Z = 4, T = 296 K, μ(Mo Kα) = 0.088 mm-1, ρ calc = 1.259 g/cm3, 13928 reflections measured (5.86° ≤ 2Θ ≤ 51.98°), 2478 unique (R int = 0.1613, R σ = 0.1335). The final R 1 was 0.1098 (I ≥ 2u(I)), and wR 2 was 0.2183. The antibacterial activity for both crude extract of leaves and quinoline dione was determined by a well diffusion method. The quinoline dione alkaloid demonstrated excellent inhibition zones against methicillin-resistant Staphylococcus aureus (18 mm), Bacillus subtills (17 mm), Escherichia coli (20 mm), and Pseudomonas aeruginosa (23 mm) compared to the crude extract. The antibiofilm potential was recorded against Pseudomonas aeruginosa by the 96-well microtiter plate method. A dose-dependent biofilm inhibition response was recorded, which increased with the increase in concentration. Moreover, quinoline dione showed a greater antibiofilm effect as compared to the crude extract, which may be linked to the presence of a particular active functional group positioned on the compound isolated in its pure form. Through in silico studies, i.e., molecular docking, quinoline dione shows strong binding energies with the LasR transcriptional regulator (6MVN) at -9.3 and LasR transcriptional activator (3IX4) at -9.2 kcal/mol, as well as moderate affinities with other targets such as AHL synthase LasI (PDB ID 1RO5) and OprM channel (PDB ID 3D5K), indicating its potential as a quorum sensing inhibitor. Thus, the antibacterial and antibiofilm potential of quinoline dione was confirmed.

Site differentiation strategy for selective strontium uptake and elution within an all-inorganic polyoxoniobate framework

Selective uptake and elution of trace amounts of hazardous radioactive 90Sr from large-scale high-level liquid waste (HLW) is crucial for sustainable development. Here, we propose a site differentiation strategy, based on the presence of distinct selective metal capture sites (concavity site and tweezer site) within the giant polyoxoniobate (PONb) nanoclusters of an all-inorganic PONb framework (FZU-1). Through this strategy, FZU-1 can not only effectively remove 98.9% of Sr²⁺ from simulated nuclear liquid waste, performing best among the reported Sr adsorbents, but also achieve desorption of adsorbed Sr²⁺ ions by selectively loading Na⁺ ions, thus enabling the recycling of FZU-1. Based on the well-defined single-crystal structures and theoretical studies, it can be revealed that the rapid and selective uptake of Sr²⁺ is attributed to the strong binding energy between the Sr²⁺ ions and the concavity sites. The effective elution of Sr²⁺, on the other hand, stems from the preferential binding of Na⁺ ions at the tweezer sites, elevating the cluster’s electrostatic potential and indirectly facilitating the elution of Sr²⁺ ions. The exceptional stability of FZU-1, along with its rapid and selective Sr²⁺ capture and elution capabilities, positions it as a promising candidate for large-scale nuclear waste treatment and groundwater remediation applications.

α-GLUCOSIDASE AND TYROSINASE INHIBITORY GUIDED ISOLATION, IDENTIFICATION OF MAJOR COMPOUND AND IN SILICO STUDY FROM EDIBLE MUSHROOM COPRINUS COMATUS

Coprinus comatus is an edible and medicinal mushroom. The crude hexane, EtOAc and methanol extracts were extracted successively from C. Comatus. All the crude extracts were evaluated for anti-a-glucosidase and tyrosinase. The results showed that %inhibition valued for the crude hexane, EtOAc and methanol extracts of anti-a-glucosidase were 98.58 ± 0.09, 98.90 ± 0.21, and 6.68 ± 0.79, respectively. The anti-tyrosinase for the crude hexane, EtOAc and methanol extracts were 97.31 ± 2.77, 97.31 ± 3.34 and 64.94 ± 3.34, respectively. Notably, the bioassay-guided showed that the crude hexane and EtOAc were the highest for anti-a-glucosidase and tyrosinase activities, which led to the interest in purifying the major compound. The isolation and purification were successively done using chromatographic techniques. The pure compounds were determined by spectroscopic analysis (UV, FTIR, and NMR) and comparison with previously reported. The isolation led to three compounds (1-3), ergosterol (1), indole-3-carbaldehyde (2), and 4-hydroxybenzoic acid (3). The molecular docking of compounds 1-3, reported as α-glucosidase and tyrosinase inhibitors, was done by the AutoDockTools 1.5.6 (ADT) software. The results revealed that ergosterol (1) provides the highest binding free energy (-9.91 kcal/mol) to the active site of a-glucosidase, indicating that it is quite specific to this enzyme. Moreover, ergosterol (1) has strong binding energy (-9.64 kcal/mol) to tyrosinase but not significant tyrosinase specificity. This evidence supports that C. Comatus would be applicable for a functional food for controlling glucose blood levels.

Development of a novel papain gel formulation: Exploring different concentrations for smear-layer deproteinization and enhanced dentin bonding

BackgroundThe self-etch adhesive system modifies but does not completely remove the smear layer, leading to the weakening of the bond strength due to the formation of a hybridized layer. Smear-layer deproteinization with papain enzyme partially removes the smear layer, and increases the bond strength with self-etch adhesive. The aim was to develop a deproteinizing agent with a high papain enzyme concentration to enhance dentin bonding with self-etch adhesives. MethodsPapain enzyme gel formulations (15 and 30 IU/g) were prepared and tested for physical stability, viscosity, pH, homogeneity, and organoleptic properties. Moreover, 64 teeth were used to test the deproteinization efficiency of the formed gel. Fourier transform infrared was used to calculate the ratio of organic to inorganic components of smear-layer after deproteinization with 15 and 30 IU/g papain gel and a 6 IU/g commercial papain gel. Moreover, tensile bond strength was measured after deproteinization and dentin bonding with self-etching adhesive for the same groups. A molecular modeling simulation was also performed to evaluate the protein-protein binding interaction, predict the conformational/orientation patterns, and estimate the binding energies of papain with collagen target protein. ResultsBoth 15 and 30 IU/g gels exhibited similar viscosity, pH, homogeneity, and organoleptic properties. However, after 60 s, the 15 IU/g gel was solid, while the 30 IU/g gel was half-solid. All tested groups decreased the amide:phosphate ratio and increased tensile bond strength. Binding complexes between papain and three deposited collagen-1 structures formed strong binding energies with high negative values and residue-wise binding patterns. ConclusionsThe production of the papain enzyme gel with a concentration of 15 IU/g was successful. In addition, it demonstrated promising results when used as a smear-layer deproteinization agent. Clinical significanceEnzymatic smear-layer deproteinization may improve dentin adhesion, and high concertation papain enzyme gels may improve dentin adhesion with the use of self-etch adhesive

Boosting the electrocatalytic performance of CuCo2S4 via surface-state engineering for ampere current water electrolysis applications

For the efficient production of green H2 on an industrial scale, developing durable, cost-effective electrocatalysts using earth-abundant transition-metals is crucial. Herein, we report a robust, bifunctional sulfurized CuCo2O4 (CCS/Ov) catalyst with engineered oxygen-vacancies, in which the metal catalyst is tunes to high valence state, significantly altering the intrinsic reaction kinetics and generating better catalytic activity for efficient ion transport in various electrolytes (neutral, seawater, alkaline simulated-seawater (ASW), and KOH). The optimized dual-strategy synthesized CCS/Ov catalysts with hierarchical morphology exhibits modest overpotential of 383 and 355 mV at 1000 mA cm−2 for OER and HER, respectively, in 1 M KOH. Impressively, an electrolyzer cell (CCS/Ov||CCS/Ov) demonstrates low cell-voltage of 1.487 V (6 M KOH), with excellent robustness in an ASW (1 and 2 M) environment against corrosive chlorine. The bifunctional CCS/Ov||CCS/Ov catalyst outperforms a state-of-the-art paired Pt/C||RuO2 catalyst and maintains the lowest potential response at up to 2000 mA cm−2, while demonstrating remarkably stable simultaneous O2 and H2 generation over 10 days at various current rates. Additionally, DFT calculations confirmed that CCS/Ov catalysts demonstrate significantly enhanced HER and OER activities due to reduced H2O dissociation energy and strong intermediate binding energy, which is attributed to the anionic vacancy near Co3+. The excellent bifunctional performance of the hierarchical CCS/Ov highlights its potential as non-precious catalyst with facile fabrication approach.

Effects of Curcumin on Radiation/Chemotherapy-Induced Oral Mucositis: Combined Meta-Analysis, Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

The study aims to investigate the effects of curcumin on radiation/chemotherapy-induced oral mucositis (R/CIOM) and preliminarily explore its mechanism. Randomized controlled trials were identified from the PubMed, Embase, Web of Science, Cochrane Library, Medline, and Google Scholar databases. RevMan 5.4 was used for statistical analysis to calculate the combined risk ratios (RRs). The mechanism was analyzed through network pharmacology, molecular docking, and a molecular dynamics simulation. The targets of curcumin were collected in HERB, PharmMapper, Targetnet, Swiss Target Prediction, and SuperPred. OMIM, GeneCards, and Disgenet were used to collect relevant targets for R/CIOM. Cytoscape software 3.8.0 was used to construct the component-target-pathway network. Protein-Protein Interaction (PPI) networks were constructed using the STRING database. GO and KEGG enrichment analyses were performed by Metascape. AutoDock Vina 4.2 software was used for molecular docking. The molecular dynamics simulation was performed by Gromacs v2022.03. It is found that 12 studies involving 565 patients were included. Meta-analyses showed that curcumin reduced the incidence of severe R/CIOM (RR 0.42 [0.24, 0.75]) and the mean severity of R/CIOM (MD -0.93 [-1.34, -0.52]). Eleven core target genes were identified in the treatment of R/CIOM with curcumin. The results of molecular docking and the molecular dynamics simulation showed that curcumin had strong binding energy and stability with target proteins including MAPK3, SRC, and TNF. Overall, these findings suggest curcumin can effectively improve severe R/CIOM, perhaps by affecting MAPK3, SRC, and TNF.

Safe, Facile, and Straightforward Fabrication of Poly(N‐vinyl imidazole)/Polyacrylonitrile Nanofiber Modified Separator as Efficient Polysulfide Barrier Toward Durable Lithium–Sulfur Batteries

AbstractLithium–sulfur (Li–S) batteries are gaining tremendous attention as promising energy storage solutions due to their impressive energy density and the affordability of sulfur. However, the practical use of Li–S batteries encounter major obstacles such as the polysulfide shuttle effect, which leads to capacity loss and decreased cycling stability. Herein, a polyethylene imidazole/polyacrylonitrile (PVIMPAN) nanofibers‐modified Celgard separator is constructed via a facile electrospinning strategy and used as a polysulfides barrier for Li–S batteries. The electron‐deficient imidazole groups introduced on the surface of PVIMPAN separators create a barrier that prevents polysulfide shuttling and extends cycle life. Additionally, the developed PVIMPAN separator exhibits a significantly enhanced Li+ transfer number of 0.60, compared to the commercial Celgard separator (0.20). This enhancement can be attributed to the strong binding energy between imidazole groups and bis(trifluoromethanesulphonyl)imide anion, leading to improved Li plating and stripping performance. Consequently, incorporating the PVIMPAN separator into Li–S batteries enable the achievement of a discharge capacity of 786.0 mAh g−1 with close to 100% Coulombic efficiency after 500 cycles at 1C (25 °C). It is believed that this work can provide valuable insights for designing suitable and robust separators for metal–sulfur batteries.

In vitro antibacterial, antioxidant, in silico molecular docking and ADEMT analysis of chemical constituents from the roots of Acokanthera schimperi and Rhus glutinosa

Acokanthera schimperi is a medicinal plant traditionally used for the treatment of wounds, scabies, and malaria. Rhus glutinosa has been also utilized for the management of ectoparasites and hemorrhoids. Silica gel column chromatography separation of CH2Cl2/MeOH (1:1) extract root of A. schimperi afforded oleic acid (1), lupeol (2), dihydroferulic acid (3), acovenosigenin A- 3-O-α-L-rhamnopyranoside (4) and sucrose (5) whereas CH2Cl2/ MeOH (1:1) and MeOH roots extracts of R. glutinosa afforded β-sitosterol (6), (E)-5-(heptadec-14-en-1-yl)-4,5-dihydroxycyclohex-2-enone (7), methyl gallate (8), and gallic acid (9). The structures of the compounds were established using spectroscopic (1D and 2D NMR) and FT-IR techniques. Disc diffusin and DPPH assay were used, respectively, to evaluate the antibacterial and antioxidant potential of the extracts and isolated compounds. MeOH extract root of A. schimperi showed a modest antibacterial effect against E.coli with an inhibition zone (ZI) of 16 ± 0.0 mm compared to ciprofloxacin (ZI of 27.0 ± 0.0 mm). CH2Cl2/MeOH (1:1) and MeOH root extracts of R. glutinosa showed maximum activity against S. aureus with ZI of 17.3 ± 0.04 and 18.0 ± 0.0 mm, respectively. At 5 mg/mL, the highest activity was noted against S. aureus by 8 with ZI of 18.6 ± 0.08 mm. Dihydroferulic acid (3), methyl gallate (8), and gallic acid (9) displayed potent scavenging of DPPH radical with respective IC50 of 10.66, 7.48, and 6.08 µg/mL, compared with ascorbic acid (IC50 of 5.83 µg/mL). Molecular docking results showed that lupeol (2) exhibited strong binding energy of -7.7 and − 10 kcal/mol towards PDB ID: 4F86 and PDB ID: 3T07, respectively, compared to ciprofloxacin (-6.5 and − 7.2 kcal/mole). Towards PDB ID: 1DNU receptor, compounds 3, 8, and 9 showed minimum binding energy of -5.1, -4.8, and − 4.9 kcal/mol, respectively, compared to ascorbic acid (-5.7 kcal/mol). The Swiss ADME prediction results indicated that compounds 2, 3, 8, and 9 obeyed the Lipinksi rule of five and Veber rule with 0 violations. The in vitro antibacterial and antioxidant results supported by in silico analysis indicated that compounds 2, 3, 8, and 9 can potentially be lead candidates for the treatment of pathogenic and free radical-induced disorders.

Aromatic Residues in Proteins: Re-Evaluating the Geometry and Energetics of π-π, Cation-π, and CH-π Interactions.

Aromatic residues can participate in various biomolecular interactions, such as π-π, cation-π, and CH-π interactions, which are essential for protein structure and function. Here, we re-evaluate the geometry and energetics of these interactions using quantum mechanical (QM) calculations, focusing on pairwise interactions involving the aromatic amino acids Phe, Tyr, and Trp and the cationic amino acids Arg and Lys. Our findings reveal that π-π interactions, while energetically favorable, are less abundant in structured proteins than commonly assumed and are often overshadowed by previously underappreciated, yet prevalent, CH-π interactions. Cation-π interactions, particularly those involving Arg, show strong binding energies and a specific geometric preference toward stacked conformations, despite the global QM minimum, suggesting that a rather perpendicular T-shape conformation should be more favorable. Our results support a more nuanced understanding of protein stabilization via interactions involving aromatic residues. On the one hand, our results challenge the traditional emphasis on π-π interactions in structured proteins by showing that CH-π and cation-π interactions contribute significantly to their structure. On the other hand, π-π interactions appear to be key stabilizers in solvated regions and thus may be particularly important to the stabilization of intrinsically disordered proteins.

Deciphering Cathepsin K inhibitors: a combined QSAR, docking and MD simulation based machine learning approaches for drug design

ABSTRACT Cathepsin K (CatK), a lysosomal cysteine protease, contributes to skeletal abnormalities, heart diseases, lung inflammation, and central nervous system and immune disorders. Currently, CatK inhibitors are associated with severe adverse effects, therefore limiting their clinical utility. This study focuses on exploring quantitative structure–activity relationships (QSAR) on a dataset of CatK inhibitors (1804) compiled from the ChEMBL database to predict the inhibitory activities. After data cleaning and pre-processing, a total of 1568 structures were selected for exploratory data analysis which revealed physicochemical properties, distributions and statistical significance between the two groups of inhibitors. PubChem fingerprinting with 11 different machine-learning classification models was computed. The comparative analysis showed the ET model performed well with accuracy values for the training set (0.999), cross-validation (0.970) and test set (0.977) in line with OECD guidelines. Moreover, to gain structural insights on the origin of CatK inhibition, 15 diverse molecules were selected for molecular docking. The CatK inhibitors (1 and 2) exhibited strong binding energies of −8.3 and −7.2 kcal/mol, respectively. MD simulation (300 ns) showed strong structural stability, flexibility and interactions in selected complexes. This synergy between QSAR, docking, MD simulation and machine learning models strengthen our evidence for developing novel and resilient CatK inhibitors.