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Dengue virus, an arbovirus of genus Flavivirus, is an infectious disease causing organisms in the tropical environment leading to numerous deaths every year. No therapeutic is available against the virus till date with only symptomatic relief available. Here, we have tried to design therapeutic compounds from scratch by fragment based method followed by pharmacophore based modelling to find suitable similar structure molecules and validated the same by MD simulation, followed by binding energy calculations and ADMET analysis. The receptor binding region of the dengue envelope protein was considered as the target for prevention of viral host cell entry and thus infection. This resulted in the final selection of kanamycin as a stable binding molecule against the Dengue virus envelope protein receptor binding domain. This study results in selection of a single molecule having high binding energy and prominent stable interactions as determined by post simulation analyses. This study aims to provide a direction for development of small molecule therapeutics against the dengue virus in order to control infection. This study may open a new avenue in the arena of structure based and fragment based therapeutic design to obtain novel molecules with therapeutic potential. [ABSTRACT FROM AUTHOR]

With the aim of finding the plant-derived allosteric inhibitors of caspase-3/-7, we conducted computational investigations of bioactive compounds present in various berry fruits. In a molecular docking study, perulactone demonstrated excellent binding affinity scores of −12.1 kcal/mol and −9.1 kcal/mol for caspase 7 and 3, respectively, whereas FDA-approved allosteric inhibitors (DICA and FICA) were found to show lower docking scores (−5.6 and −6.1 kcal/mol) against caspase 7 while (−5.0 and −5.1 kcal/mol) for caspase 3, respectively. MD simulations were used to validate the binding stability of perulactone in the active sites of caspase-7/-3, and the results showed outstanding stability with lower ligand RMSDs of 1.270–3.088 Å and 2.426–9.850 Å against the targeted receptor. Furthermore, we performed MMGBSA free binding energy, where the perulactone values of ΔGBind were determined to be −63.98 kcal/mol and −66.32 kcal/mol for both receptors (3IBF and 1NME), which are significantly better than the −45.16 kcal/mol and −39.51 kcal/mol for DICA as well as −26.37 kcal/mol and −15.50 kcal/mol for FICA, respectively. The drug resemblance of perulactone was effectively evaluated by ADMET. Thus, our findings indicated that perulactone could be an orally administered therapeutic candidate for regulating apoptosis in a variety of disorders. However, there may be an urgent need to study using in vitro and in vivo experiments. [ABSTRACT FROM AUTHOR]

Cystic fibrosis transmembrane conductance regulator (CFTR) protein is an ion channel found in numerous epithelia and controls the flow of water and salt across the epithelium. The aim of our study to find natural compounds that can improve lung function for people with cystic fibrosis (CF) caused by the p.Gly628Arg (rs397508316) mutation of CFTR protein. The sequence of CFTR protein as a target structure was retrieved from UniProt and PDB database. The ligands that included Armepavine, Osthole, Curcumin, Plumbagine, Quercetin, and one Trikafta (R*) reference drug were screened out from PubChem database. Autodock vina software carried out docking, and binding energies between the drug and the target were included using docking-score. The following tools examined binding energy, interaction, stability, toxicity, and visualize protein-ligand complexes. The compounds having binding energies of −6.4, −5.1, −6.6, −5.1, and − 6.5 kcal/mol for Armepavine, Osthole, Curcumin, Plumbagine, Quercetin, and R*-drug, respectively with mutated CFTR (Gly628Arg) structure were chosen as the most promising ligands. The ligands bind to the mutated CFTR protein structure active sites in hydrophobic bonds, hydrogen bonds, and electrostatic interactions. According to ADMET analyses, the ligands Armepavine and Quercetin also displayed good pharmacokinetic and toxicity characteristics. An MD simulation for 200 ns was also established to ensure that Armepavine and Quercetin ligands attached to the target protein favorably and dynamically, and that protein-ligand complex stability was maintained. It is concluded that Armepavine and Quercetin have stronger capacity to inhibit the effect of mutated CFTR protein through improved trafficking and restoration of original function. [ABSTRACT FROM AUTHOR]

The Mercury Sulphohalides have attracted significant attention in the fields of solar cells and thermoelectric applications. This study delves into the fundamental characteristics, including structural, elasticity, electronic behavior, phonon stability, optical properties, and transport features of AgHgSZ (Z = Br, I) through computational simulations based on Density Functional Theory (DFT) using WIEN2k software. Meticulous calculations of the phonon band structure ensure dynamic stability. The semiconductor nature with indirect band gaps (1.833 eV and 1.832 eV) for Mercury Sulphohalides (Br, I), as revealed by their band structures, suggests diverse photovoltaic and transport applications. Mechanical assessments show stable ductility for AgHgSBr and brittleness for AgHgSI, along with anisotropy and resistance to scratching. Optical properties exhibit anisotropy and significant UV absorption. Analysis of effective masses, exciton binding energy, and exciton Bohr radius suggests low exciton binding energy and classification under Mott-Wannier excitons. Positive thermopower results indicate holes as the predominant charge carriers in AgHgSBr and AgHgSI materials. Moreover, essential thermoelectric factors are examined, revealing the compounds' potential for thermoelectric applications. Notably, the figure of merit (ZT) at 300 K for AgHgSBr and AgHgSI are calculated to be 0.41 and 0.13, respectively. While these values are low at 300 K, they indicate promising potential for thermoelectric applications at higher temperatures. In summary, this investigation provides valuable understanding into the photovoltaic and thermoelectric properties of AgHgSZ (Z = Br, I) materials, potentially paving the way for further exploration in this domain. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Context: The DNAN/DNB eutectic is a high-energy explosive eutectic with superior safety and thermal stability compared to traditional melt-cast explosives. However, the addition of polymer binders can effectively enhance its mechanical properties, allowing for continued production demands without the need for changes to existing factory equipment. In this paper, a model of the DNAN/DNB eutectic explosive was established, and five different types of polymers—cis-1,4-polybutadiene (BR), ethylene–vinyl acetate copolymer (EVA), polyethylene glycol (PEG), fluorinated polymer (F2603), and polyvinylidene fluoride (PVDF)—were added to the (1 0 − 1), (1 0 1), and (0 1 1) cleavage planes, respectively, to form polymer-bonded explosives (PBXs). The stability, trigger bond length, mechanical properties, and detonation performance of the various polymer-bound PBXs were predicted retrogressively. Among the five PBX models, the DNAN/DNB/PEG model exhibited the highest binding energy and the shortest trigger bond length, indicating a significant improvement in stability, compatibility, and sensitivity compared to the original eutectic. Additionally, although the detonation performance of DNAN/DNB decreased after the addition of binders, the final results were still satisfactory. Overall, the DNAN/DNB/PEG model demonstrated excellent comprehensive performance, proving that among the many polymer binders, PEG is the optimal choice for DNAN/DNB. Methods: Within the Materials Studio software, molecular dynamics (MD) simulations were employed to predict the properties of the DNAN/DNB eutectic PBX. The MD simulation timestep was set to 1 fs, with a cumulative simulation duration of 2 ns. A 2 ns MD simulation was conducted using the isothermal-isobaric ensemble (NPT). The COMPASS force field was applied, and the temperature was fixed at 295 K. [ABSTRACT FROM AUTHOR]

The presence of hydrogen traps within a metallic alloy influences the rate of hydrogen diffusion. The electro-permeation (EP) test can be used to assess this: the permeation of hydrogen through a thin metallic sheet is measured by suitable control of hydrogen concentration on the front face and by recording the flux of hydrogen that exits the rear face. Additional insight is achieved by the more sophisticated three stage EP test: the concentration of free lattice hydrogen on the front face is set to an initial level, is then dropped to a lower intermediate value and is then restored to the initial level. The flux of hydrogen exiting the rear face is measured in all three stages of the test. In the present study, a transient analysis is performed of hydrogen permeation in a three stage EP test, assuming that lattice diffusion is accompanied by trapping and de-trapping. The sensitivity of the three stage EP response to the depth and density of hydrogen traps is quantified. A significant difference in permeation response can exist between the first and third stages of the EP test when the alloy contains a high number density of deep traps. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) van der Waals layered materials have been widely used as lubricant. Penta-graphene (PG), a 2D carbon allotrope exclusively composed of irregular carbon pentagons has recently been predicted to have superlubricating property. In the present study, by combining the molecular dynamics simulation and first-principles calculations, we investigated the frictional property of PG in both commensurate and incommensurate contacts. Our calculations show the ultra-low friction at the interface of relatively rotated bilayer PG with twist angles of more than 10° away from the commensurate configuration. Meanwhile, our calculations demonstrate the isotropy of the ultra-low friction at the interface of incommensurate contact, in contrast to the anisotropic of the commensurate contacting interface. Additionally, the evolution of friction force and the fluctuation of potential energy along sliding path correlate closely with the interface's structure. The energetics and charge density explain the difference between the friction at the interfaces of the commensurate and incommensurate contacts. Not only that, we found the correlation between the intrinsic structural feature and interlayer binding energy. Importantly, our findings on the retainment of the ultra-low friction under work conditions indicates that the superlubricating state of PG has good practical adaptability. [ABSTRACT FROM AUTHOR]

Common half-cell measurements deliver oxygen reduction activities linked to the chosen scan rate, limiting their value for fundamental and comparative studies on platinum. Here we show a deconvolution of the intrinsic kinetics from the effect of surface oxygen on platinum. We find an electronic effect of the surface oxygen, substantiate a Tafel slope of ~120 mV/decade, obtain an exchange current density of 13 ± 4 µA/cm2, and an activity of 7 mA/cm2 at 900 mV. Eventually, we broaden the scope of this analysis to the effects of surface rearrangement, alloying, and supported Pt nanoparticles, the latter providing insight into discrepancies between half-cell and fuel cell measurements. We find through computational methods that binding energies of intermediates would be weakened by the presence of highly coordinated oxygen atoms. Finally, we obtain a phenomenological rate equation for the oxygen reduction and evolution reaction, suggesting that both reactions follow a shared mechanism. Catalyzing the splitting and formation of oxygen on noble metal surfaces are key reactions developing materials for electrolysis. Here, authors show on platinum that the state of a surface oxidation process is a key descriptor for the kinetics. [ABSTRACT FROM AUTHOR]

Plant-derived phytochemicals from medicinal plants are becoming increasingly attractive natural sources of antimicrobial and antiviral agents due to their therapeutic value, mechanism of action, level of toxicity and bioavailability. The continued emergence of more immune-evasive strains and the rate of resistance to current antiviral drugs have created a need to identify new antiviral agents against SARS-CoV-2. This study investigated the antiviral potential of balsaminol, a bioactive compound from Momordica balsamina, and its inhibitory activities against SARS-CoV-2 receptor proteins. In this study, three Food and Drug Administration (FDA) COVID-19 approved drugs namely; nirmatrelvir, ritonavir and remdesivir were used as positive control. Molecular docking was performed to determine the predominant binding mode (most negative Gibbs free energy of binding/ΔG) and inhibitory activity of balsaminol against SARS-CoV-2 receptor proteins. The pharmacokinetics, toxicity, physicochemical and drug-like properties of balsaminol were evaluated to determine its potential as an active oral drug candidate as well as its non-toxicity in humans. The results show that balsaminol E has the highest binding affinity to the SARS CoV-2 papain-like protease (7CMD) with a free binding energy of − 8.7 kcal/mol, followed by balsaminol A interacting with the spike receptor binding domain (6VW1) with − 8.5 kcal/mol and balsaminol C had a binding energy of − 8.1 kcal/mol with the main protease (6LU7) comparable to the standard drugs namely ritonavir, nirmatrelvir and remdesivir. However, the ADMET and drug-like profile of balsaminol F favours it as a better potential drug candidate and inhibitor of the docked SARS-CoV-2 receptor proteins. Further preclinical studies are therefore recommended. [ABSTRACT FROM AUTHOR]

Molecules involved in solvation shells have properties differing from those of the bulk solvent, which can in turn affect reactivity. Among key properties of these molecules are their nature and electronic structure. Widely used tools to characterize this type of property are X-ray-based spectroscopies, which, however, usually lack the capability to selectively probe the solvation-shell molecules. A class of X-ray triggered "non-local" processes has the recognized potential to provide this selectivity. Intermolecular Coulombic decay (ICD) and related processes involve neighbouring molecules in the decay of the X-ray-excited target, and are thus naturally sensitive to its immediate environment. Applying electron spectroscopy to aqueous solutions, we explore the resonant flavours of ICD and demonstrate how it can inform on the first solvation shell of excited solvated cations. One particular ICD process turns out to be a potent marker of the formation of ion pairs. Another gives a direct access to the electron binding energies of the water molecules in the first solvation shell, a quantity previously elusive to direct measurements. The resonant nature of the processes makes them readily measurable, providing powerful new spectroscopic tools. X-ray triggered non-local processes, such as Intermolecular Coulombic Decay, are shown here to selectively probe solvation-shell molecules in solution and provide new information on their electronic structure and on ion-pair formation. [ABSTRACT FROM AUTHOR]

In this work, we have reported the design, synthesis, in vitro, and in silico enzymatic evaluation of new bis-4-hydroxycoumarin-based phenoxy-1,2,3-triazole-N-phenylacetamide derivatives 5a-m as potent α-glucosidase inhibitors. All the synthesized analogues showed high inhibition effects against α-glucosidase (IC50 values ranging between 6.0 ± 0.2 and 85.4 ± 2.3 µM) as compared to the positive control acarbose (IC50 = 750.0 ± 0.6 µM). Among the newly synthesized compounds 5a-m, 2,4-dichloro-N-phenylacetamide derivative 5i with inhibition effect around 125-folds more than the acarbose was identified as the most potent entry. A structure–activity relationship (SAR) study about the title compounds 5a-m demonstrated that the inhibition effects of these compounds depend on the pattern of substitution on the N-phenylacetamide ring. The interaction modes and binding energies in the active site of enzyme of the important analogues (in term of SAR study) were evaluated through molecular docking study. Molecular dynamics and prediction of pharmacokinetic properties and toxicity of the most potent compound 5i also evaluated and the obtained data was compared with the acarbose. [ABSTRACT FROM AUTHOR]

Semiconducting transition metal dichalcogenides (MX2) occur in 2H and rhombohedral (3R) polytypes, respectively distinguished by anti-parallel and parallel orientation of consecutive monolayer lattices. In its bulk form, 3R-MX2 is ferroelectric, hosting an out-of-plane electric polarisation, the direction of which is dictated by stacking. Here, we predict that twin boundaries, separating adjacent polarisation domains with reversed built-in electric fields, are able to host two-dimensional electrons and holes with an areal density reaching ~ 1013cm−2. Our modelling suggests that n-doped twin boundaries have a more promising binding energy than p-doped ones, whereas hole accumulation is stable at external surfaces of a twinned film. We also propose that assembling pairs of mono-twin films with a 'magic' twist angle θ* that provides commensurability between the moiré pattern at the interface and the accumulated carrier density, should promote a regime of strongly correlated states of electrons, such as Wigner crystals, and we specify the values of θ* for homo- and heterostructures of various TMDs. The authors investigate the twin boundaries in ferroelectric transition metal dichalcogenides, predicting their trap electrons with low densities, enhancing electron-electron interactions and potentially promoting Wigner crystallisation. [ABSTRACT FROM AUTHOR]

Resonant inelastic x-ray scattering (RIXS) is a widely used spectroscopic technique, providing access to the electronic structure and dynamics of atoms, molecules, and solids. However, RIXS requires a narrow bandwidth x-ray probe to achieve high spectral resolution. The challenges in delivering an energetic monochromated beam from an x-ray free electron laser (XFEL) thus limit its use in few-shot experiments, including for the study of high energy density systems. Here we demonstrate that by correlating the measurements of the self-amplified spontaneous emission (SASE) spectrum of an XFEL with the RIXS signal, using a dynamic kernel deconvolution with a neural surrogate, we can achieve electronic structure resolutions substantially higher than those normally afforded by the bandwidth of the incoming x-ray beam. We further show how this technique allows us to discriminate between the valence structures of Fe and Fe2O3, and provides access to temperature measurements as well as M-shell binding energies estimates in warm-dense Fe compounds. The authors combine differentiable physics modelling and neural networks to extract high-resolution electronic density of states of warm dense materials from resonant inelastic x-ray scattering spectra. With this approach, they identify distinctive features in the valence structures of warm dense Fe and Fe2O3, also estimating their temperature and M-shell binding energies. [ABSTRACT FROM AUTHOR]

Globoid cell leukodystrophy is a severe rare disorder characterized by white matter degradation, resulting in a progressive loss of physical and mental abilities and has extremely limited therapeutic interventions. Therefore, this study aimed to delve into the Globoid cell leukodystrophy associated intricate network of differentially expressed genes (p < 0.05, |Fc|> 1) to identify potential druggable targets and possible therapeutic interventions using small molecules. The disease-associated neuronal protein circuit was constructed and analyzed, identifying 53 nodes (minimum edge cutoff 1), among which five (FOS, FOSB, GDNF, GFRA1, and JUN) were discerned as potential core protein nodes. Although our research enumerates the potential small molecules to target various protein nodes in the proposed disease network, we particularly underscore T-5224 to inhibit c-Jun activity as JUN was identified as one of the pivotal elements within the disease-associated neuronal protein circuit. The evaluation of T-5224 binding energy (− 11.0 kcal/mol) from docking study revealed that the compound to exhibit a notable affinity towards Jun/CRE complex. Moreover, the structural integrity of complex was affirmed through comprehensive molecular dynamics simulations, indicating a stable hydrophilic interaction between T-5224 and the Jun/CRE complex, thereby enhancing protein compactness and reducing solvent accessibility. This binding energy was further substantiated by free binding analysis, revealing a substantial thermodynamics complex state (− 448.00 ± 41.73 kJ/mol). Given that this investigation is confined to a computational framework, we additionally propose a hypothetical framework to ascertain the feasibility of inhibiting the Jun/CRE complex with T-5224 against Globoid cell leukodystrophy, employing a combination of in vitro and in vivo methodologies as a prospective avenue of this study. [ABSTRACT FROM AUTHOR]

Polyphenol oxidase (PPO) is an industrially important enzyme associated with browning reactions. In the present study, a set of ten new dihydropyridine [2,3-d] pyrimidines (TD-Hid-1-10) were synthesized and was found to be proven characteristically by 1H NMR, 13C NMR, IR, elemental analysis, and assessed as possible PPO inhibitors. PPO was purified from banana using three-phase partitioning, achieving an 18.65-fold purification and 136.47% activity recovery. Enzyme kinetics revealed that the compounds TD-Hid-6 and TD-Hid-7 are to be the most potent inhibitors, exhibiting mixed-type inhibition profile with IC50 values of 1.14 µM, 5.29 µM respectively against purified PPO enzyme. Electronic structure calculations at the B3LYP/PBE0 level of theories using def-2 SVP, def2-TZVP basis sets with various molecular descriptors characterized the electronic behavior of studied derivatives TD-Hid-1-10. Molecular electrostatic potential (MEP) and reduced density gradient analyses of RDG-NCI provided insights into charge distributions and weak intermolecular interactions. Docking study simulations predicted binding poses within crucial amino acid sequence in the 2y9x enzyme's active site, which is typically similar in sequence to the PPO form is not allowed. Ligands were analysed in terms of binding energies, inhibitor concentrations (mM) and various molecular interactions such as H-bonds, H-carbon, π-carbon, π-sigma, π-sigma, π-π T-shaped, π-π stacked, π-alkyl, Van der Waals and Cu interactions. The lowest binding energy (-7.83 kcal/mol) and the highest inhibitory effect (1.83 mM) were shown by the ligand Td-Hid-6, which forms H-bonds with Met280 and Asn260, exhibits π-sigma interactions with His61 and π-alkyl interactions with Val283. Other ligands also showed different interactions with various amino acids; for example, the Td-Hid-1 ligand formed H-bonds with His244 and showed π-sigma interactions with His244 and Val283. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most prevalent cancer types in the world and accounts for the majority of cases of primary liver cancer. A crucial part of the carcinogenesis of HCC involves aberrant stimulation of the FGF19-FGFR4 signaling pathway. Therefore, FGFR4 inhibition has become a strategic therapeutic approach for the treatment of HCC. However, the clinical treatment procedure is significantly hampered by the prevalence of kinase inhibitors resistance. It was recently established that the activation of EGFR signaling was found to be one of the primary mechanisms mediating the acquired resistance to FGFR4 inhibitors, moreover, sensitivity to FGFR4 inhibitors was effectively restored by inhibiting EGFR. These results provide compelling evidence that dual inhibition of EGFR and FGFR4 could represent a viable therapeutic approach to overcome resistance, hence enhanced management of HCC. To this end, we proposed a dual irreversible inhibition strategy through covalent binding by naturally occurring electrophilic warhead-bearing compounds (curcumin, deoxyelephantopin, eupalmerin acetate, syringolin A and andrographolide) to covalently target both EGFR and FGFR4 through cysteine residues, Cys797 and Cys552, respectively. Covalent docking and covalent molecular dynamics (MM/MDcov) simulations combined with thermodynamic binding free energy calculations were performed, and the results were compared against known potent and selective covalent EGFR and FGFR4 inhibitors with available X-ray crystal structures, Afatinib and BLU9931, respectively. Curcumin, deoxyelephantopin, eupalmerin acetate, syringolin A, and andrographolide showed relative binding free energies of -22.85, -17.14, -12.98, -21.81, and − 19.00 kcal/mol against EGFR and − 41.06, -29.45, -24.76, -40.11, and − 37.55 kcal/mol against FGFR4, respectively. The mechanisms of binding were emphasized by hydrogen bonding and binding forces analysis as well as active site physicochemical profiling. The findings of this study identified that curcumin, syringolin A and andrographolide—but not eupalmerin acetate or deoxyelephantopin —could be viable dual EGFR and FGFR4 covalent irreversible inhibitors and could be implemented in HCC combination therapy protocols alone or in conjunction with other chemotherapeutic agents. Investigations of this study conclusively indicate dual blockade of EGFR and FGFR4 may be a promising future therapeutic strategy for enhanced management of HCC. [ABSTRACT FROM AUTHOR]

In the present study, some hybrid compounds containing 1,2,3-triazole and naphthalene subunits 16(a–g) and 17(a–f) were synthesized and characterized by 1H, 13C-NMR, FT-IR, and HR-MS analyses. The in vitro inhibitor activities on the xanthine oxidase (XO) enzyme of all the target compounds were investigated and compared with allopurinol, which is one of the most common gout drugs and inhibits the XO. The activity results show that all the target compounds have potential XO inhibitor activities. The compounds showed IC50 values in the range of 0.825–2.254 μM on the XO. IC50 value of allopurinol on the XO was determined to be 1.475 μM. 16e and 17e compounds among them exhibited the best inhibitions compared to other compounds and allopurinol. Additionally, molecular docking studies were carried out on the 3D crystallographic structure of the XO to investigate possible interactions with the active site of the XO of all compounds. According to the docking results, all the target compounds showed that the best binding energies vary in the between − 9.71 kcal.mol−1 and − 11.43 kcal.mol−1. Finally, in silico ADME and toxicity properties of the compounds were investigated using the Swiss ADME, ProTox-II, and Osiris Property Explorer websites and it has been predicted that the target compounds have low toxicity profiles. Consequently, the compounds can be considered new promising inhibitors for the XO. [ABSTRACT FROM AUTHOR]

The properties of isospin-asymmetric cold nuclear matter are studied in terms of the relativistic mean-field theory in which, besides the fields of σ, ω, and ρ mesons, and the isovector, Lorentz-scalar field of the δ-meson is also taken into account. The properties of purely nucleonic np matter are studied as a function of the baryon density nB and the asymmetry parameter α, as well as the properties of electrically neutral β-equilibrium npe μ matter as a function of the baryon density nB. For different values of nB and a, such characteristics of np matter as the energy per baryon, the specific energy owing to isospin asymmetry, the effective proton and neutron masses, and the specific binding energy, are determined. It is shown that the energy owing to the asymmetry for a fixed value of α is a monotonically increasing function of the baryon density nB. For npem matter, the effective proton and neutron masses M p e f f , M n e f f , the specific binding energy Ebind, the symmetry energy Esym, the quantitative fraction of protons Yp = np/nB are studied, as well as the average meson fields σ ~ , ω ~ , δ ~ , and ρ ~ as functions of the baryon density nB. [ABSTRACT FROM AUTHOR]

Objective: It is worthy to note that the benzimidazole, thiazolidine-2,4-dione and 1,2,3-triazole pharmacophores have keen role in anticancer drug discovery. In order to overcome the limitations associated with reported antimitotic compounds, our group is first time combining these three pharmacophores and revealing their in vitro anticancer and anti-mitotic activities. Methods: As a part of our efforts on the development of novel anticancer agents, in this study, we concentrated on the synthesis of benzimidazole-thiazolidine-2,4-dione-1,2,3-triazoles (VIIa-–VIIl) via piperidine catalyzed Knoevenagel condensation and Cu(I) catalyzed azide-alkyne cycloaddition reactions as key approaches. Then, in vitro anticancer and tubulin polymerization inhibition (VIIa–VIIl) were studied via IC50 values. Finally, docking interactions of three potent compounds (VIIg), (VIIh), and (VIIk) towards α,β-tubulin were studied using AutoDock tools. Results and Discussion: Three compounds namely (VIIg), (VIIh), and (VIIk) showed better results against A549, MCF-7, and HeLa human cancer cell lines than standard drug nocodazole. In addition, compounds (VIIg) and (VIIh) have shown greater inhibitory potency with IC50 values 0.62 and 0.31 μM respectively than standard Combretastatin A-4 (CA-4) against tubulin polymerization. Finally, in silico molecular docking studies for the compounds (VIIg), (VIIh), and (VIIk) with α,β-tubulin showed that they have great binding interactions with the target protein and to be specific the compound (VIIh) displayed highest binding energy, i.e. –9.23 kcal/mol. Conclusions: We propose that the remarkable in vitro anticancer activity of compounds (VIIg), (VIIh), and (VIIk), would be due to their tubulin polymerization inhibition. [ABSTRACT FROM AUTHOR]

Molecules were proposed to block the functional cycles of the influenza virus A and SARS-CoV-2. The blocker molecules efficiently bind inside the M2 and E channels of influenza A and SARS-CoV-2 viruses and block diffusion of H+/K+ ions, thus distorting the virus functional cycle. A family of positively charged (+2 e.u.) molecular blockers of H+/K+ ion diffusion through the M2 and E channels was proposed. The blocker molecules were diazabicyclooctane (DABCO) derivatives and were investigated for affinity for the M2 and E channels. Thermal dynamics of native and mutant channel structures and blocker binding were modeled by exhaustive docking. Binding energy calculations revealed within-channel, blocking, and extra-channel binding sites in the M2 and E channel proteins. Blocker molecules with higher affinity for the blocking sites were proposed. The most probable amino acid mutations the M2 and E channels were considered, the efficiency of channel blocking was analyzed, and optimal structures were assumed for the blocker molecules. [ABSTRACT FROM AUTHOR]

Context: Diabetes mellitus (DM) is a metabolic disorder disease that causes hyperglycemia conditions and associated with various chronic complications leading to mortality. Due to high toxicity of conventional diabetic drugs, the exploration of natural compounds as alternative diabetes treatments has been widely carried out. Previous in silico studies have highlighted berberine, a natural compound, as a promising alternative in antidiabetic therapy, potentially acting through various pathways, including the inhibition of the FOXO1 transcription factor in the gluconeogenesis pathway. However, the specific mechanism by which berberine interacts with FOXO1 remains unclear, and research in this area is relatively limited. Therefore, this study aims to determine the stability of berberine structure with FOXO1 based on RMSD, RMSF, binding energy, and trajectory analysis to determine the potential of berberine to inhibit the gluconeogenesis pathway. This research was conducted by in silico method with molecular docking using AutoDock4.2 and molecular dynamics study using Amber20, then visualized by VMD. Methods: Docking between ligand and FOXO1 receptor was carried out with Autodock4.2. For molecular dynamics simulations, the force fields of DNA.OL15, protein.ff14SB, gaff2, and tip3p were used. [ABSTRACT FROM AUTHOR]

The potential use of organic electronic materials in various optoelectronic devices has drawn considerable attention in recent years. For organic electronic devices to operate more effectively, the exciton binding energy must be reduced. Using high-throughput screening methods and machine learning analyses, a thorough framework for creating organic electronic materials with lower exciton binding energies has been described in the current research. Our approach combines computer simulations, databases of materials, and data-driven algorithms to find viable compounds for materials with low exciton binding energies. Python software has been used to analyze various ML models. Breaking retrosynthetically interesting chemical substructures methodology has been used to form new compounds. The characteristics of compounds has been represented through molecular descriptors. Random forest regressor model, gradient boosting regressor model, K Neighbors regressor model and extra tree regressor model have been used to analyze the performance parameters. Twenty organic semi-conductors have been selected with low Eb values. The synthetic accessibility score indicated easy synthesis of selected semi-conductors. Similarity analysis has indicated structural similarity between selected semi-conductors. Machine learning is helping the potential use of organic electronic materials in various optoelectronic devices, such as organic photovoltaics, organic light-emitting diodes, and organic field-effect transistors. [ABSTRACT FROM AUTHOR]

Defect levels induced by defect-complexes in Ge play important roles in device fabrication, characterization, and processing. However, only a few defect levels induced by defect-complexes have been studied, hence limiting the knowledge of how to control the activities of numerous unknown defect-complexes in Ge. In this study, hybrid density functional theory calculations of defect-complexes involving oversize atom (indium) and n-type impurity atoms in Ge were performed. The formation energies, defect-complex stability, and electrical characteristics of induced defect levels in Ge were predicted. Under equilibrium conditions, the formation energy of the defect-complexes was predicted to be within the range of 5.90–11.38 eV. The defect-complexes formed by P and In atoms are the most stable defects with binding energy in the range of 3.31-3.33 eV. Defect levels acting as donors were induced in the band gap of the host Ge. Additionally, while shallow defect levels close to the conduction band were strongly induced by the interactions of Sb, P, and As interstitials with dopant (In), the double donors resulting from the interactions between P, As, N, and the host atoms including In atom are deep, leading to recombination centers. The results of this study could be applicable in device characterization, where the interaction of In atom and n-type impurities in Ge is essential. This report is important as it provides a theoretical understanding of the formation and control of donor-related defect-complexes in Ge. [ABSTRACT FROM AUTHOR]

Composite dielectric materials with different dielectric characteristics are crucial for energy storage devices. In this study, a composite material of 5 wt.% metal (M)/bentonite (Bento) (M = Cd, Cu, Fe, or Zn) was synthesized using a wet impregnation technique to examine the effect of metal incorporation in bentonite. X-ray diffraction, scanning electron microscopy, energy-dispersive x-ray analysis, and impedance analysis were carried out to investigate the structural, morphological, electrical, and dielectric properties of the samples. A low-frequency dielectric response provided evidence of dielectric relaxation, which was associated with local charge polarizations occurring at the grain (or particle) site. A reduction in the dielectric constant was observed in metal-doped composites, attributed to the variation in grain size and the resulting change in the dipole number per unit volume generated by doping. Interestingly, the AC conductivity dispersion decreased for dopants with a larger ionic radius, in line with qualitative expectations. Tight-binding calculations demonstrated that the changes in binding energy, hardness, and the positioning of the highest occupied molecular orbital and lowest unoccupied molecular orbital of Bento were responsible for the differences in dielectric properties resulting from the incorporation of different metals into Bento. Thus, our results demonstrate the successful metal doping-induced tunability of the dielectric and structural properties of Bento, with significant implications for its use as supercapacitor (optimal dopant is Fe, as it induces larger permittivity), and hence its polarizability. The lowest permittivity was achieved for Cd doping, suggesting its potential use for insulator applications. [ABSTRACT FROM AUTHOR]

The contraction of CAG/CTG repeats is an attractive approach to correct the mutation that causes at least 15 neuromuscular and neurodegenerative diseases, including Huntington's disease and Myotonic Dystrophy type 1. Contractions can be achieved in vivo using the Cas9 D10A nickase from Streptococcus pyogenes (SpCas9) using a single guide RNA (sgRNA) against the repeat tract. One hurdle on the path to the clinic is that SpCas9 is too large to be packaged together with its sgRNA into a single adeno-associated virus. Here we aimed to circumvent this problem using the smaller Cas9 orthologue, SlugCas9, and the Cas9 ancestor OgeuIscB. We found them to be ineffective in inducing contractions, despite their advertised PAM sequences being compatible with CAG/CTG repeats. Thus, we further developed smaller Cas9 hybrids, made of the PAM interacting domain of S. pyogenes and the catalytic domains of the smaller Cas9 orthologues. We also designed the cognate sgRNA hybrids using molecular dynamic simulations and binding energy calculations. We found that the four Cas9/sgRNA hybrid pairs tested in human cells failed to edit their target sequences. We conclude that in silico approaches can identify functional changes caused by point mutations but are not sufficient for designing larger scale complexes of Cas9/sgRNA hybrids. [ABSTRACT FROM AUTHOR]

Within the context of Molecular Electronic Density Theory (MEDT), this study investigates the Diels–Alder reaction among isoprene (2) and R-carvone (1R) applying DFT simulations, with and without Lewis acid (LA) catalysis. The results show that carvone (1R) acts as an electrophile and isoprene (2) as a nucleophile in a polar process. LA catalysis increases the electrophilicity of carvone, thereby improving the reactivity and selectivity of the reaction by reducing the activation Gibbs free energy. Parr functions reveal that the C5=C6 double bond is more reactive than the C9=C10 double bond, indicating chemoselectivity. The examination of the Electron Localization Function (ELF) reveals high regio- and stereoselectivity, indicating an asynchronous mechanism for the LA-catalyzed DA reaction. Furthermore, it is suggested that cycloadduct 3 has great anti-HIV potential because it exhibits lower binding energies than azidothymidine (AZT) in the docking studies of cycloadducts 3 and 4 amongst a primary HIV-1protein (1A8O plus 5W4Q). [ABSTRACT FROM AUTHOR]

Developing devices with a wide-temperature range persistent photoconductivity (PPC) and ultra-low power consumption remains a significant challenge for optical synaptic devices used in neuromorphic computing. By harnessing the PPC properties in materials, it can achieve optical storage and neuromorphic computing, surpassing the von Neuman architecture-based systems. However, previous research implemented PPC required additional gate voltages and low temperatures, which need additional energy consumption and PPC cannot be achieved across a wide temperature range. Here, we fabricated a simple heterojunctions using zinc(II)-meso-tetraphenyl porphyrin (ZnTPP) and single-walled carbon nanotubes (SWCNTs). By leveraging the strong binding energy at the heterojunction interface and the unique band structure, the heterojunction achieved PPC over an exceptionally wide temperature range (77 K-400 K). Remarkably, it demonstrated nonvolatile storage for up to 2×104 s, without additional gate voltage. The minimum energy consumption for each synaptic event is as low as 6.5 aJ. Furthermore, we successfully demonstrate the feasibility to manufacture a flexible wafer-scale array utilizing this heterojunction. We applied it to autonomous driving under extreme temperatures and achieved as a high impressive accuracy rate as 94.5%. This tunable and stable wide-temperature PPC capability holds promise for ultra-low-power neuromorphic computing. Devices with a wide-temperature range persistent photoconductivity (PPC) and low power consumption is a challenge for optical synaptic devices in neuromorphic computing. Here, the authors develop a carbon nanotube/porphyrin heterojunction on a flexible array, achieving PPC between 77 K to 400 K. [ABSTRACT FROM AUTHOR]

The issue of antibiotic resistance in pathogenic microbes is a global concern. This study was aimed to explore in silico and in vitro analysis of the antibacterial efficacy of different natural ligands against bacterial activity. The ligands included in the study were Propolis Neoflavanoide 1, Carvacrol, Cinnamaldehyde, Thymol, p-benzoquinone, and Ciprofloxacin (standard drug S*). The outcomes of molecular docking revealed that Propolis Neoflavaniode-1 showed a highly significant binding energy of − 7.1 and − 7.2 kcal/mol for the two gram-positive bacteria, as compared to the gram-negative bacteria. All ligands demonstrated acute toxicity (oral, dermal), except for Propolis Neoflavanoide 1 and S* drugs, with a confidence score range of 50–60%. Using a molecular dynamic simulation approach, we investigated Propolis Neoflavaniode-1's potential for therapeutic use in more detail. An MD simulation lasting 100 ns was performed using the Desmond Simulation software to examine the conformational stability and steady state of Propolis Neoflavaniode-1 in protein molecule complexes. Additionally, in vitro studies confirmed the antimicrobial activity of Propolis Neoflavaniode 1 by increasing the zone of inhibition against Gram-positive bacteria, p < 0.005 as compared to gram-negative bacteria. This study revealed the promising antibacterial efficacy of Propolis Neoflavaniode 1, demonstrated through robust in silico analyses, minimal toxicity, and confirmed in vitro antimicrobial activity, suggesting its potential as a viable alternative to combat antibiotic resistance. [ABSTRACT FROM AUTHOR]

Type-II transmembrane serine proteases are effective pharmacological targets for host defence against viral entry and in certain cancer cell progressions. These serine proteases cleave viral spike proteins to expose the fusion peptide for cell entry, which is essential to the life cycle of the virus. TMPRSS2 inhibitors can also fight against respiratory viruses that employ them for cell entry. Our study combining virtual screening, all-atom molecular dynamics, and well-tempered metadynamics simulation identifies vicenin-2, neohesperidin, naringin, and rhoifolin as promising TMPRSS2 antagonists. The binding energies obtained are − 16.3, − 15.4, − 13.6, and − 13.8 kcal/mol for vicenin-2, neohesperidin, naringin, and rhoifolin respectively. The RMSD, RMSF, PCA, DCCM, and binding free energy profiles also correlate with the stable binding of these ligands at the active site of TMPRSS2. The study reveals that these molecules could be promising lead molecules for combating future outbreaks of coronavirus and other respiratory viruses. [ABSTRACT FROM AUTHOR]

The present work reports the synthesis of pure V2O5 and Ni-doped V2O5 nanoparticles via co-precipitation method, exploring diverse concentrations of Ni2+ in V2O5 system. The valent reduction of V, Ni, Oxygen stabilization and formation of V2O5 and Ni-doped V2O5 nanoparticles were evident by characterization techniques such as X-ray diffraction, Fourier transform infrared spectroscopy, Photoluminescence and UV–Visible Diffuse Reflectance Spectroscopy. Bandgap variations and Crystallite size of pure V2O5 and Ni-doped V2O5 nanoparticles confirmed the reduction of Ni+ and V+ their difference was found to be ∆Eg = 1.52 eV and 24–43 nm, respectively. X-ray Photoelectron Spectroscopy analysis examined oxidation states and binding energies which is vital for understanding structural and compositional aspects. Evaluation of bacterial endurance against gram-positive (S. aureus) and gram-negative bacteria (E.coli), coupled with antioxidant activity measurements via 2,2-Diphenyl-1-picrylhydrazyl (DPPH) method, indicate the successful utilization of the synthesized nanoparticles for biomedical and wastewater treatment applications. In contagious diseases, Ni/V2O5 nanoparticles showed superior activity against both S. aureus and E. coli. Photocatalytic activity against MB (98%) and Rh–B (88%) dyes under visible light irradiation was also evaluated with Ni/V2O5 nanoparticles which is exhibiting enhanced performance. Pseudo-first-order kinetics revealed accelerated dye degradation upon Ni ion incorporation, suggesting improved electron–hole pair activity and ROS formation. The AOP facilitated by the photocatalyst holds promise for wastewater treatment, with advantages such as absence of secondary product formation and presence of activated electrons. The in-depth investigation about the properties of Ni2+ into V2O5 lead us towards the cost effective and multifunctional applications of these nanoparticles at industrial level. [ABSTRACT FROM AUTHOR]

An efficient one-pot multi-component reaction (MCR) of 2,3-dihydro-4(1H)-quinazolinone derivative achieved by the reaction of aryl/heteroaryl aldehyde, isatoic anhydride and substituted aniline in ethanol catalyzed by novel glutamic acid (Glu) under microwave irradiation is described. In this work, derivatives 4m, 4o, 4q and 4r are novel compounds among the synthesized derivatives. For the first time, the electrochemical behavior studies for the selected derivatives were tested using cyclic voltammetry, compounds 4l, 4m, 4p, 4o, and 4q showed good reducing and oxidizing potential, due to the presence of the functional groups. Molecular docking studies of the selected compounds (4l–r) verified, among them highest docking scored 4r and 4m (− 8.572 and − 8.959 kcal/mol) molecules, respectively. Furthermore, MM/PBSA calculation identified key residues that contribute to the binding energy, activity and assessed cytotoxicity. The in vitro anticancer evaluation of the synthesized compounds was tested against human ovarian cancer PA-1 cell line tested; compounds 4r and 4m exhibited exceptionally anti-proliferative activity very close to the reference drug doxorubicin (3.66 ± 0.07) with the IC50 value 7.53 ± 0.09 and 17.93 ± 0.12, respectively. According to swissADME study, the blood–brain barrier can be crossed majority of the derivatives tested, except 4n, and have high gastrointestinal absorption. [ABSTRACT FROM AUTHOR]

CsPbBr3 nanoplatelets (NPLs) have gained significant attention as promising blue-emitting materials due to their large exciton binding energy and narrow full width at half-maximum (FWHM) of emission spectra. However, the weak binding ability of ligands to the surface of pure blue-emitting CsPbBr3 NPLs results in reduced optical properties and stability. Here, a ligand passivation strategy was developed for synthesizing monodisperse pure blue-emitting CsPbBr3 NPLs with enhanced photoluminescence (PL) by incorporating phenylalanine (PHE) ligands during NPLs growth. Due to the simultaneous interaction of the amino and carboxyl groups of PHE with the lead halide octahedron formed, the growth of CsPbBr3 NPLs in the vertical direction is inhibited, while the surface defects of the NPLs prepared are effectively passivated. As a result, combined with the post-treatment with oleamine bromide (OAmBr), the synthesized monodisperse CsPbBr3 NPLs show an emission peak centered at 461 nm with a narrow FWHM of 16 nm and a PLQY value of 98%. [ABSTRACT FROM AUTHOR]

To improve the efficacy of organic solar cells (OSCs), novel small acceptor molecules (CTD1–CTD7) were designed by modification at the terminal acceptors of reference compound CTR. The optoelectronic properties of the investigated compounds (CTD1–CTD7) were accomplished by employing density functional theory (DFT) in combination with time-dependent density functional theory (TD-DFT). The M06 functional along with a 6-311G(d,p) basis set was utilized for calculating various parameters such as: frontier molecular orbitals (FMO), absorption maxima (λmax), binding energy (Eb), transition density matrix (TDM), density of states (DOS), and open circuit voltage (Voc) of entitled chromophores. A red shift in the absorption spectra of all designed chromophores (CTD1–CTD7) was observed as compared to CTR, accompanied by low excitation energy. Particularly, CTD4 was characterized by the highest λmax value of 685.791 nm and the lowest transition energy value of 1.801 eV which might be ascribed to the robust electron-withdrawing end-capped acceptor group. The observed reduced binding energy (Eb) was linked to an elevated rate of exciton dissociation and substantial charge transfer from central core in HOMO towards terminal acceptors in LUMO. These results were further supported by the outcomes from TDM and DOS analyses. Among all entitled chromophores, CTD4 exhibited bathochromic shift (685.791 nm), minimum HOMO/LUMO band gap of 2.347 eV with greater CT. Thus, it can be concluded that by employing molecular engineering with efficient acceptor moieties, the efficiency of photovoltaic materials could be improved. [ABSTRACT FROM AUTHOR]

Effective thermal transport across solid-solid interfaces, essential in thermal interface materials (TIMs), necessitates both optimal thixotropy and high thermal conductivity. The role of filler surface modification, a fundamental aspect of TIM fabrication, in influencing these properties is not fully understood. This study employs the use of a silane coupling agent (SCA) to modify alumina, integrating experimental approaches with molecular dynamics simulations, to elucidate the interface effects on thixotropy and thermal conductivity in polydimethylsiloxane (PDMS)-based TIMs. Our findings reveal that varying SCAs modify both interface binding energy and transition layer thickness. The interface binding energy restricts macromolecular segmental relaxation near the interface, hindering desirable thixotropy and bond line thickness. Conversely, the transition layer thickness at the interface positively influences thermal conductivity, facilitating phonon transport between the polymer and filler. Consequently, selecting an optimal SCA enables a balance between traditionally conflicting goals of high thermal conductivity and minimal bond line thickness, achieving an impressively low interface thermal resistance of just 2.45–4.29 K·mm2·W−1 at 40 psi. [ABSTRACT FROM AUTHOR]

The dehydrated chemical sludge has a strong water-holding capacity and is difficult to treat further and utilize. To explore the internal mechanism of sludge beam water, the molecular dynamics simulation method was used to study the interaction between Curdlan polysaccharide and water. The effects of water content, temperature, and chain number of polysaccharides on the binding capacity of polysaccharides were analyzed. The radial distribution function, number of hydrogen bonds, binding energy, etc., characterized the interaction properties. It was found that polysaccharides mainly use hydrogen bonding to bind water molecules, and the hydroxyl group connected to the main chain has the most vital binding capacity; the saturated water content of a single chain was 44.14%. The binding energy at different temperatures was also calculated. The results showed that 358 K was the critical point. When the temperature exceeds 358 K, the polysaccharide and water molecules turn from attraction to repulsion. At this time, polysaccharide molecules can no longer bind most of the water molecules in the system; the water molecules move more freely. Additionally, the increased number of polysaccharide chains will increase the interconnectedness to each other and wrap water molecules inside the polysaccharide molecules, then solidified water on the polysaccharide's surface, enhancing the polysaccharide's water bunching capacity. [ABSTRACT FROM AUTHOR]

Context: To estimate the influence of temperature on properties of 2,4,6,8,10,12-hexanitro- 2,4,6,8,10,12-hexaazaisowurtzitane/1,4-dinitroimidazole (CL-20/1,4-DNI) cocrystal explosive, the supercell crystal of CL-20/1,4-DNI cocrystal model was established. The mechanical properties, sensitivity, and stability of cocrystal model under different temperatures (T = 225 K, 250 K, 275 K, 300 K, 325 K, 350 K) were predicted. Results show that mechanical parameters, including bulk modulus, tensile modulus and shear modulus are the lowest when temperature is 300 K, while Cauchy pressure is the highest, indicating that CL-20/1,4-DNI cocrystal model has better mechanical properties at 300 K. Cohesive energy density (CED) and its components energies decrease monotonically with the increase of temperature, illustrating that the CL-20 and 1,4-DNI molecules are activated and the safety of cocrystal explosive is worsened with the increase of temperature. Cocrystal model has relatively higher binding energy when the temperature is 300 K, implying that the CL-20/1,4-DNI cocrystal explosive is more stable under this condition. Methods: The CL-20/1,4-DNI cocrystal model was optimized and the properties were predicted through molecular dynamics (MD) method. The MD simulation was performed with COMPASS force field and the ensemble was set as NPT, external pressure was set as 0.0001 GPa. [ABSTRACT FROM AUTHOR]

Context: SARS-CoV-2, responsible for COVID-19, has led to over 500 million infections and more than 6 million deaths globally. There have been limited effective treatments available. The study aims to find a drug that can prevent the virus from entering host cells by targeting specific sites on the virus's spike protein. Method: We examined 13,397 compounds from the Malaria Box library against two specific sites on the spike protein: the receptor-binding domain (RBD) and a predicted cryptic pocket. Using virtual screening, molecular docking, molecular dynamics, and MMPBSA techniques, they evaluated the stability of two compounds. TCMDC-124223 showed high stability and binding energy in the RBD, while TCMDC-133766 had better binding energy in the cryptic pocket. The study also identified that the interacting residues are conserved, which is crucial for addressing various virus variants. The findings provide insights into the potential of small molecules as drugs against the spike protein. [ABSTRACT FROM AUTHOR]

The ion selectivity of 18-crown-6 (18C6) ether has been investigated by DFT method. The following conclusions are drawn with the analyses about the geometrical structure, the binding energy, the natural bond orbital charge population, the infrared spectra, and the spin-spin coupling constant. First of all, the ion selectivity of 18C6 attributes primarily to the valence state, the periodic number, and the volume of the cation. Secondly, for the cation encapsulated complex of the same main group, the variation of distance between two para-oxygen atoms in the complex and in 18C6 (ΔROO) is proportionate to the binding energy of cation and 18C6. Then, the cation, bearing most of the electropositive charges, is encapsulated in the center of six electronegative oxygen atoms. Fourthly, the value of spin-spin coupling constant of cation and peripheral oxygen atom (1J(M, O)) mainly dominated by the Fermi-contact term. The swing of cation along the para-position oxygen atoms is typical and can be taken as a characteristic for ion recognition. [ABSTRACT FROM AUTHOR]

Systematic investigation of energy levels of Λ hypernuclei enables physicists to determine a considerable number of details about the inner structure of these particles as well as the interaction dynamics of Λ nucleon. Of importance is to develop the theoretical tools to study spectroscopy of hypernuclei. In this regard, our aim is to specify the mass spectra and the binding energies of Λ hypernuclei in their ground and excited states. Then, we first present an analytical solution for the Bethe–Salpeter equation of single Λ hypernuclei taking the Woods–Saxon interaction potential. Through a good approximation, we present an analytical expression for the binding energies in the ground and excited states, i.e., 1p, 1d, 1f and 1g shells. We also give numerical results for Λ binding energies of light and heavy hypernuclei. Our numerical analysis is compared with experimental data so that good consistencies between both results confirm the approach used to analysis the Λ–nucleon interaction. [ABSTRACT FROM AUTHOR]

N-vinylformamide (NVF) was successfully grafted onto a bacterial cellulose (BC) sheet through gamma radiation-induced simultaneous grafting. The optimum conditions for grafting were an irradiation dose of 15 kGy and an NVF concentration of 30%vol. The resulting product, poly(vinyl formamide)-grafted-bacterial cellulose sheet (PNVF-g-BC) was hydrolyzed using a basic medium to obtain poly(vinyl amine)-grafted-BC (PVAm-g-BC) as an eco-friendly dye adsorbent. The maximum degrees of NVF grafting and hydrolysis were 98.89 ± 3.95% and 88 ± 0.55%, respectively. Chemical, binding energy, crystalline, thermal, and morphological characterizations of the starting materials, as well as PNVF-g-BC and PVAm-g-BC adsorbents, were conducted. Batch tests were performed to investigate the efficiency of methylene blue (MB) adsorption and the adsorption capacity of the PVAm-g-BC adsorbent. The effects of initial MB concentration, time, and pH on the adsorption were studied. The maximum adsorption capacity of the adsorbent was 7.78 ± 0.41 mg/g at an MB concentration of 10 mg/L, pH 13, and a reaction time of 8 h. The adsorption behavior of MB onto the adsorbent was found to fit the Langmuir isotherm model, indicating monolayer adsorption. The adsorption/desorption study demonstrated that the adsorbents could be reused for 6 cycles with effective performance for MB adsorption (> 50%). This eco-friendly dye adsorbent exhibits outstanding properties as a potential candidate for dye adsorption. [ABSTRACT FROM AUTHOR]

The growing interest in a material composed of Cu single atoms and/or their sub-nanometric clusters deposited on titania prompted us to perform systematic theoretical studies on the system comprising the anatase phase of titania, modelled by a (TiO2)34 cluster with copper particles of 1–7 atoms on top of it. The ground-state geometric structures were proposed and compared with the available literature data derived from EXAFS experiments done for Cu-TiO2 materials. Copper atoms prefer to aggregate and form larger clusters on TiO2, as seen from the computed nucleation energies. The models were characterised by the following electronic properties: electronic band structure, natural population charges, and frontier orbitals (HOMO, LUMO, and SOMO). The copper phase becomes oxidised once it is deposited on titania. The charge distribution in the resulting structures indicates that the atoms that are the closest to the Cu-TiO2 interface would become the active sites for catalytic processes; copper atoms would act as electrophilic, while oxygen atoms would act as nucleophilic. The calculated binding energies between the two phases show that the formation of the composite system is favourable from the thermodynamic point of view, and the interaction between the small copper clusters and the titania surface is mostly of electrostatic nature. [ABSTRACT FROM AUTHOR]

Understanding the properties of lithium vacancy, LiCV, defects in diamond is crucial for optimizing diamond-based semiconductor performance and unlocking its full potential in advanced electronic applications. In this study, we present a comprehensive theoretical investigation of the neutral LiCV defect, resulting from the interaction between a lithium substitutional and a vacancy, in diamond. Employing periodic supercell calculations, we utilize global (B3LYP and PBE0) and range-separated (HSE06) hybrid functionals, as well as a local basis set, within the CRYSTAL17 code to analyze the relaxed lattice structure, formation energy, magnetic properties, and electronic structures of LiCV and other related isolated defects (LiC V and 2V). Our results reveal that LiCV exhibits three distinct spin states (doublet, quartet, and sextet) with significant differences in spin density distributions on first-neighbor carbon atoms. The quartet state is energetically favored by 0.09 eV and 0.88 eV (B3LYP) compared to the doublet and sextet states, respectively. The Li atom is positioned midway between the two vacancies in the LiCV defect, exhibiting a local D3d symmetry. Our findings reveal that the LiCV defect exhibits remarkable stability within the diamond matrix, with its dissociation into LiC and a vacancy (V) demanding a substantial energy barrier of 6.07 eV. In environments rich in vacancies, LiC shows a strong preference for binding with these vacancies, thereby facilitating the formation of LiCV complexes. Raman scattering calculations offer intriguing insights into the LiCV defect, revealing distinctive spectral features that significantly aid in distinguishing this particular defect among isolated lithium LiC and vacancy (V) defects. This observation is crucial, especially considering the challenges in fabricating shallow donors involving interstitial lithium in diamond, where preexisting vacancies can significantly influence the process. The comprehensive analysis provided in this study not only deepens our understanding of the LiCV defect and its physical properties but also enhances our ability to detect this defect during the synthetic process, and to precisely control the formation conditions. This capability is vital for optimizing the electronic properties of diamond for advanced technological applications. [ABSTRACT FROM AUTHOR]

Cytosolic Glycerol-3-phosphate dehydrogenase 1 (GPD1, EC 1.1.1.8) plays a pivotal role in regulating the Embden-Meyerhof glucose glycolysis pathway (E-M pathway), as well as in conditions such as Huntington's disease, cancer, and its potential role as a specific marker for Dormant Glioma Stem Cells. In this study, we conducted virtual screening using the ZINC database (http://zinc.docking.org/) and the GPD1 structure to identify potential GPD1 modulators. The investigation involved screening active candidate ligands using ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) parameters, combined with molecular docking, pose analysis, and interaction analysis based on Lipinski and Veber criteria. Subsequently, the top 10 ligands were subjected to 200 ns all-atom molecular dynamics (M.D.) simulations, and binding free energies were calculated. The findings revealed that specific residues, namely TRP14, PRO94, LYS120, ASN151, THR264, ASP260, and GLN298, played a crucial role in ensuring system stability. Furthermore, through a comprehensive analysis involving molecular docking, molecular M.D., and DeLA-Drug, we identified 10 promising small molecules. These molecules represent potential lead compounds for developing effective therapeutics targeting GPD1-associated diseases, thereby contributing to a deeper understanding of GPD1-associated mechanisms. This study's significance lies in identifying key residues associated with GPD1 and discovering valuable small molecules, providing a foundation for further research and development. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs), mainly caused by thrombosis complications, are the leading cause of mortality worldwide, making the development of alternative treatments highly desirable. In this study, the thrombolytic potential of green kiwifruit (Actinidia deliciosa cultivar Hayward) was assessed using in-vitro and in-silico approaches. The crude green kiwifruit extract demonstrated the ability to reduce blood clots significantly by 73.0 ± 1.12% (P < 0.01) within 6 h, with rapid degradation of Aα and Bβ fibrin chains followed by the γ chain in fibrinolytic assays. Molecular docking revealed six favorable conformations for the kiwifruit enzyme actinidin (ADHact) and fibrin chains, supported by spontaneous binding energies and distances. Moreover, molecular dynamics simulation confirmed the binding stability of the complexes of these conformations, as indicated by the stable binding affinity, high number of hydrogen bonds, and consistent distances between the catalytic residue Cys25 of ADHact and the peptide bond. The better overall binding affinity of ADHact to fibrin chains Aα and Bβ may contribute to their faster degradation, supporting the fibrinolytic results. In conclusion, this study demonstrated the thrombolytic potential of the green kiwifruit-derived enzyme and highlighted its potential role as a natural plant-based prophylactic and therapeutic agent for CVDs. [ABSTRACT FROM AUTHOR]

In exploring nature's potential in addressing diabetes-related conditions, this study investigates the therapeutic capabilities of 3-formyl chromone derivatives. Utilizing in silico methodologies, we focus on 6-substituted 3-formyl chromone derivatives (1–16) to assess their therapeutic potential in treating diabetes. The research examined the formyl group at the chromone's C-3 position. ADMET, biological activities, were conducted along with B3LYP calculations using 3 different basis sets. The analogues were analyzed based on their parent structure obtained from PubChem. The HOMO–LUMO gap confirmed the bioactive nature of the derivatives, NBO analysis was performed to understand the charge transfer. PASS prediction revealed that 3-formyl chromone derivatives are potent aldehyde oxidase inhibitors, insulin inhibitors, HIF1A expression inhibitors, and histidine kinase. Molecular docking studies indicated that the compounds had a strong binding affinity with proteins, including CAD, BHK, IDE, HIF-α, p53, COX, and Mpro of SARS-CoV2. 6-isopropyl-3-formyl chromone (4) displayed the highest affinity for IDE, with a binding energy of − 8.5 kcal mol−1. This result outperformed the affinity of the reference standard dapagliflozin (− 7.9 kcal mol−1) as well as two other compounds that target human IDE, namely vitexin (− 8.3 kcal mol−1) and myricetin (− 8.4 kcal mol−1). MD simulations were revealed RMSD value between 0.2 and 0.5 nm, indicating the strength of the protein–ligand complex at the active site. [ABSTRACT FROM AUTHOR]

Excitons, pairs of electrons and holes, undergo a Bose-Einstein condensation at low temperatures. An important platform to study excitons is double-layer two-dimensional electron gases, with two parallel planes of electrons and holes separated by a thin insulating layer. Lowering this separation (d) strengthens the exciton binding energy, however, leads to the undesired interlayer tunneling, resulting in annihilation of excitons. Here, we report the observation of a sequences of robust exciton condensates (ECs) in double bilayer graphene twisted to ~ 10° with no insulating mid-layer. The large momentum mismatch between two graphene layers suppresses interlayer tunneling, reaching a d ~ 0.334 nm. Measuring the bulk and edge transport, we find incompressible states corresponding to ECs when both layers are in half-filled N = 0, 1 Landau levels (LLs). Theoretical calculations suggest that the low-energy charged excitation of ECs can be meron-antimeron or particle-hole pair, which relies on both LL index and carrier type. Our results establish a novel platform with extreme coupling strength for studying quantum bosonic phase. Previous studies of exciton condensates in moire heterostructures have been limited to large layer separation or one carrier type. Here the authors report a complete sequence of exciton condensates at both electron and hole fillings in large-angle twisted double bilayer graphene without a spacer layer. [ABSTRACT FROM AUTHOR]

Background: Allergic disorders, prevalent global health concerns, afflict a substantial portion of the world's population. These maladies result from an exaggerated immune system response to ordinarily innocuous substances, such as pollen, dust mites, and specific dietary components. Clinical manifestations of this heightened immune response include itching, swelling, and respiratory impairment, often accompanied by releasing mediators like histamine. The pathophysiological mechanisms of allergy disorders are intricate, arising from a complex interplay between genetic and environmental factors. While clinical presentations may vary, all allergy conditions share a common foundation in the dysregulated immune response to allergens. Result: The current aim of this study was to identify innovative anti-allergic agents capable of inhibiting histamine and effectively mitigating allergic reactions by utilizing the computer-aided drug design approach by discovery studio (DS) 2022 v 23.1.1 package. The overarching aim was identifying potential drug candidates targeting the active site within the histamine H1 receptor complex; therefore, a collection of 4000 small druggable compounds was curated from ZINC, PubChem, and DRUG BANK databases sources. Four compounds appeared as promising candidates after assessing docking scores and binding energies. Notably, Compound ID 34154, recognized as tymazoline, showed the highest affinity for the H1 receptor of 3RZE, suggesting it may be the most promising choice for more research. Further chemoinformatic and ADMET (absorption, distribution, metabolism, excretion, and toxicity) analyses were conducted to assess the drug-like qualities of this chosen molecule. In addition, bioisosteric substitution techniques were employed to enhance tymazoline's ADMET characteristics. Conclusion: Tymazoline shows strong binding affinity with 3RZE and verified all the drug-likeness criteria to inhibit the allergic disorders. Furthermore, molecular dynamics (MD) studies corroborated tymazoline's potential as an anti-allergic agent, demonstrating contact between the ligand and the receptor that is well defined and stable. [ABSTRACT FROM AUTHOR]

A variety of new pyrido[2,3-d]pyrimidine-piperazine-1,2,4-oxadiazoles was synthesized and tested in vitro for their ability to inhibit EGFR kinases and their anti-cancer activity against two breast cancer cell lines. Compared to erlotinib, a number of the compounds exhibited acceptable activity. Among them, the most promising compounds 5-(2,4-difluorophenyl)-3-{[4-(pyrido[2,3-d]pyrimidin-4-yl)piperazin-1-yl]methyl}-1,2,4-oxadiazole, 5-(4-fluorophenyl)-3-{[4-(pyrido[2,3-d]pyrimidin-4-yl)piperazin-1-yl]methyl}-1,2,4-oxadiazole, and 5-(3,5-dichlorophenyl)-3-{[4-(pyrido[2,3-d]pyrimidin-4-yl)piperazin-1-yl]methyl}-1,2,4-oxadiazole exhibited excellent anti-cancer activity against MCF-7 cancer cell line with IC50 values of 3.79±0.61, 4.12±0.74 and 4.07±0.39 μM, respectively, as well as excellent kinase inhibitory activities (EGFR: IC50 = 0.45±0.02, 0.51±0.08 and 0.31±0.07 μM). And also 5-(2,4-difluorophenyl)-3-{[4-(pyrido[2,3-d]pyrimidin-4-yl)piperazin-1-yl]methyl}-1,2,4-oxadiazole and 5-(4-fluorophenyl)-3-{[4-(pyrido[2,3-d]pyrimidin-4-yl)piperazin-1-yl]methyl}-1,2,4-oxadiazole shown potent activity against MDA-MB-231 with IC50 values of 5.83±0.88 and 6.32±0.71 μM, respectively. To evaluate the molecular interactions of more potent compounds with the human epidermal growth factor receptor, EGFR (PDB: 4HJO) proteins and a co-crystallized ligand erlotinib. It was observed that all the compounds exhibited greater binding energies in comparison to the standard drug erlotinib. [ABSTRACT FROM AUTHOR]

In this paper, we develop a convex splitting algorithm for the time-dependent Ginzburg-Landau equation, which can preserve both the energy stability and maximum bound principle. The basic idea of the convex splitting method is to decompose the energy functional into the convex part and the concave part. The term corresponding to the convex part of the equation is implicitly treated, and the concave part is explicitly processed. The backward Euler time discretizing method is chosen for the time-dependent Ginzburg-Landau equation. The theoretical analysis proves that the convex splitting method can preserve the maximum bound principle and energy stability. The numerical results show that the numerical algorithm is stable. [ABSTRACT FROM AUTHOR]