Strong Molecular Interactions Research Articles

Tilted Spins in Chains of Molecular Switches on Pb(100).

A complex based on a Ni(II) porphyrin exhibiting spin crossover on Ag(111) is studied on Pb(100) by scanning tunneling microscopy at 0.3 K. Strong molecular interactions between the phenyl and pentafluorophenyl moieties lead to the formation of molecular chains and cause a faceting of the substrate surface. The chains are located along double and multiple substrate steps that deviate from high-symmetry directions. Tunneling spectroscopy reveals spin-flip excitations of an S = 1 system. Measurements in high magnetic fields are used to identify a tilt of the complex and its hard anisotropy axis with respect to the surface normal. Electron injection into the substrate near the molecular rows induces a transition to a state with larger inelastic cross section, leaving the spin state unchanged.

Diabetic wound healing potentials of phenylethanoid glycosides from Clerodendrum glandulosum Lindl.: Connecting the dots by integrating network pharmacology, molecular docking, and molecular dynamics simulation

The diabetic wound is one of the severe complications of diabetes mellitus, accounting for 20 % of limb amputations in diabetic patients. This creates a need to search for newer natural compounds to target the different molecular pathways of diabetic wounds to accelerate the repair. The phenylethanoid glycosides (PhGs) isolated from Clerodendrum glandulosum (CG) have been shown to exhibit antioxidant, antimicrobial, and anti-inflammatory properties but have never been explored for diabetic wound healing. Thus, this study focuses on exploring the diabetic wound-repairing properties of PhGs through in-silico approaches. The PhGs present in CG were identified through extensive literature searching, which were further subjected to database searching in BindingDB, TargetNet, PharmMapper, Super-PRED, and Swiss Target Prediction to find the potential targets, which included PRKCA, PRKCG, PRKCZ, TDP1, and Pol. Subsequently, these targets were used to determine the disease IDs related to diabetic wounds from databases such as DisGeNET, Gene Expression Omnibus, GeneCards, and OMIM. A network was established using Cytoscape to study the relationship among the PhGs, the protein targets, and their associated disease IDs. The top twenty molecular pathways associated with the target proteins were determined using the ShinyGO database. Genetic enrichment analysis showed that the Sphingolipid signalling pathway included the maximum number of genes and had the lowest false discovery rate value, which concluded that this pathway is the potential target of the PhGs. PRKCA and PRKCZ were found to be the only two genes involved in this pathway, and thus, molecular docking was used to evaluate the binding affinity of the PhGs with the proteins. Docking scores were between -13.2859 and -5.10928, suggesting a strong molecular interaction between the PhGs and their targets. Thus, it is concluded that PhGs present in CG can be the potential compounds to treat diabetic wounds; however, further in-vitro and in-vivo investigations are necessary.

Studies on interactions of L-glutamic acid with L-arabinose/D-xylose in aqueous medium: Ultrasonic velocity and acoustic parameter studies supported by FTIR spectroscopic investigation

Glutamic acid is a non-essential amino acid, meaning that the body can synthesize it on its own, and it doesn’t necessarily need to be obtained from the diet. Using an ultrasonic interferometer, the ultrasonic velocity at 293.15 K and 298.15 K and at experimental pressure P = 101 kPa were determined in order to evaluate and comprehend the synergy between non-essential amino acid and saccharides (L-arabinose/D-xylose) in an aqueous system. There is a direct correlation between the weak and strong molecular interactions that occur between the solution’s constituents and the propagation of ultrasonic sound waves through the experimental solutions. Using the ultrasonic velocity data, isentropic compressibility (Ks) apparent molar isentropic compressibility (Ks,ϕ) and isothermal compressibility (KT) were calculated. In addition to these characteristics, acoustic impedance (Z), internal pressure (πi), relative association (RA), molar free volume (Vf), molar free length (Lf) and surface tension (γ) were deduced and analysed to advocates potent ion- solvent interactions. In order to gain understanding of Glu-Glu and Glu- L-arabinose/D-xylose interactions in aqueous medium, these parameters were interpreted. Ion-solvent interactions are stronger than ion-ion interactions due to the greater and positive values of Ks0. Strong contacts occur between the polar segments of L-arabinose/D-xylose and the zwitterionic groups of Glu, and these interactions become stronger as the concentration of L-arabinose/D-xylose increases, as indicated by positive values of Ks,ϕ,tr0. The water structure is reformed during the solvation and ion association processes of Glu. Furthermore, the spectroscopic investigation has been conducted using the FTIR technique in order to verify the results obtained from acoustic studies. Predominant ion-hydrophilic/hydrophobic interactions prevail in the studied system is validated by FTIR study. Absorption band widening indicates that intermolecular hydrogen bonding predominates over intramolecular hydrogen bonding.

The Key to MOF Membrane Fabrication and Application: the Trade-off between Crystallization and Film Formation.

Metal-organic frameworks (MOFs), owing the merits of ordered and tailored channel structures in the burgeoning crystalline porous materials, have demonstrated significant promise in construction of high-performance separation membranes. However, precisely because this crystal structure with strong molecular interaction in their lattice provides robust structural integrity and resistance to chemical and thermal degradation, crystalline MOFs typically exhibit insolubility, infusibility, stiffness and brittleness, and therefore their membrane-processing properties are far inferior to the flexible amorphous polymers and hinder their subsequent storage, transportation, and utilization. Hence, focusing on film-formation and crystallization is the foundation for exploring the fabrication and application of MOF membranes. In this review, the film-forming properties of crystalline MOFs are fundamentally analyzed from their inherent characteristics and compared with those of amorphous polymers, influencing factors of polycrystalline MOF membrane formation are summarized, the trade-off relationship between crystallization and membrane formation is discussed, and the strategy solving the film formation of crystalline MOFs in recent years are systematically reviewed, in anticipation of realizing the goal of preparing crystalline membranes with optimized processability and excellent performance.

WTAP and m6A-modified circRNAs modulation during stress response in acute myeloid leukemia progenitor cells

N6-methyladenosine (m6A) is one of the most prevalent and conserved RNA modifications. It controls several biological processes, including the biogenesis and function of circular RNAs (circRNAs), which are a class of covalently closed-single stranded RNAs. Several studies have revealed that proteotoxic stress response induction could be a relevant anticancer therapy in Acute Myeloid Leukemia (AML). Furthermore, a strong molecular interaction between the m6A mRNA modification factors and the suppression of the proteotoxic stress response has emerged. Since the proteasome inhibition leading to the imbalance in protein homeostasis is strictly linked to the stress response induction, we investigated the role of Bortezomib (Btz) on m6A regulation and in particular its impact on the modulation of m6A-modified circRNAs expression. Here, we show that treating AML cells with Btz downregulated the expression of the m6A regulator WTAP at translational level, mainly because of increased oxidative stress. Indeed, Btz treatment promoted oxidative stress, with ROS generation and HMOX-1 activation and administration of the reducing agent N-acetylcysteine restored WTAP expression. Additionally, we identified m6A-modified circRNAs modulated by Btz treatment, including circHIPK3, which is implicated in protein folding and oxidative stress regulation. These results highlight the intricate molecular networks involved in oxidative and ER stress induction in AML cells following proteotoxic stress response, laying the groundwork for future therapeutic strategies targeting these pathways.

Cellulose-based eutectogel electrolyte with high ionic conductivity for solid-state lithium-ion batteries

It is known that the low ionic conductivity of solid-state polymer electrolytes at room temperature (RT) has severely restricted their practical application in lithium-ion batteries. Although eutectogel (ETG) electrolytes could solve this problem to some extent, highly compatible deep eutectic solvent (DES)/polymer systems are desirable to further enhance ion conduction. Herein, we designed cellulose-based ETG (CETG) with dual channels through “hopping” and “vehicle” mechanisms by hydroxyethyl cellulose (HEC) molecular chains and N-methylacetamide (NMA)/LiTFSI-derived DES, respectively. Thanks to the strong molecular interactions between HEC and DES, the highest DES content in the ETG could achieve 90 %, which endowed the CETG with an excellent ionic conductivity of 2.04 × 10–3 S cm−1 at 30 °C. Additionally, our designed CETG displayed good self-healing and fire retardant properties. The assembled Li/LiFePO4 cell showed a capacity retention of 91.8 % after 200 cycles at 0.2 C under RT with an initial discharge capacity of 156.2 mAh g−1. In particular, the capacity retention rates of the assembled batteries reached 95.2 % and 92.1 %, respectively, after 100 cycles at 0.2 C under 60 °C and 50 cycles at 0.2 C under 100 °C. Our fabrication strategy would provide a novel idea for the design of green, safe and efficient solid-state polymer electrolytes for lithium-ion batteries.

Utilizing the allyl-terminated copolymer methoxy(poly(ethylene glycol))-block-poly(jasmine lactone) in the development of amorphous solid dispersions: A comparative study of functionalized and non-functionalized polymer

Molecular interactions are crucial to stabilize amorphous drugs in amorphous solid dispersions (ASDs). Most polymers, however, have only a limited ability to form strong molecular interactions with drugs. Polymers tailored to fit the physicochemical properties of the drug molecule to be incorporated, for instance by allowing the incorporation of specific functional groups, would be highly sought-for in this regard. For this purpose, the novel allyl-terminated polymer methoxy(polyethylene glycol)-block-poly(jasmine lactone) (mPEG-b-PJL) has been synthesized and functionalized to potentially enhance specific drug-polymer interactions. This study investigated the use of mPEG-b-PJL in ASDs, using carvedilol (CAR), a weakly basic model drug. The findings revealed that the acidic functionalized form of the polymer (mPEG-b-PJL-COOH) indeed established stronger molecular interactions with CAR compared to its non-functionalized counterpart mPEG-b-PJL. Evaluations on polymer effectiveness in forming ASDs demonstrated that mPEG-b-PJL-COOH outperformed its non-functionalized counterpart in miscibility, drug loading ability, and stability, inferred from reduced molecular mobility. However, dissolution tests indicated that ASDs with mPEG-b-PJL-COOH did not significantly improve the dissolution behaviour compared to amorphous CAR alone, despite potential solubility enhancement through micelle formation. Overall, this study confirms the potential of functionalized polymers in ASD formulations, while the challenge of improving dissolution performance in these ASDs remains an area of further development.

Fluorinated molecular diamond improved polymer electrolytes enable stable cycling with high capacity of all-solid-state lithium-metal batteries

The interfacial incompatibility of the poly (ethylene oxide)-based electrolytes hinder the longevity and further practice of all-solid-state batteries. Herein, we present a productive additive 1-Fluoroadamantane facilitating to the distinct performance of the poly (ethylene oxide)-based electrolytes. Attributed to the strong molecular interaction, the coordination of the Li+-EO is reduced and the ‘bonding effect’ of anion is improved. Thus, the Li + conductivity is promoted and the electrochemical window is widened. The diamond building block C10H15− strengthens the stability of the solid polymer electrolytes. Importantly, the 1-Fluoroadamantane mediates the generation of LiF in the interfaces, which fosters the interfacial stability, contributing to the long-term cycling. Hence, the symmetric cell (Li/Li) exhibits a long-term lithium plating/stripping for over 2,400 h. The 4.3 V LiNi0.8Mn0.1Co0.1O2/Li all-solid-state battery with the 1-Fluoroadamantane-poly (ethylene oxide) improved electrolyte delivers 600 times, with an impressive capacity retention of 84%. Also, the cell presents high capacity of 210 mA·h/g, and 170 mA·h/g at 0.1 C and 0.3 C respectively, rivalling the liquid electrolytes.

One-Pot Biopreparation of Trimetallic ZnO–MgO–CuO Nanoparticles: Enhanced Cytotoxicity, Antibacterial Activities and Molecular Docking Studies

Nowadays, metal oxide nanoparticles (MO NPs) are powerful tools for biological applications due to their distinctive features. Moreover, the biological efficacy of multimetallic NPs is more fascinating because of their structural modifications and synergistic effects. This study utilized the one-pot green route to fabricate trimetallic ZnO-MgO-CuO (ZMC) NPs employing a greener reducing agent from Artemisiaabyssinica leaf extract (AALE). The crystal structure, size, compositions, shapes, and external topology of ZMC NPs were characterized by Fourier transform infrared (FTIR), UV–Visible (UV–vis), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), and transmission electron microscopy combined with selected area electron diffraction (TEM/HRTEM-SAED). The outcomes suggested that the bio-prepared ZMC NPs are highly crystalline and have hexagonal structures lattice with monoclinic symmetry and spherical morphology with average crystalline and particle sizes of 14.67 and 15.13 nm, respectively. Using MTT assay, the bio-prepared ZMC NPs demonstrated high inhibition percentage (94.37 ± 0.14 at 250 mg/mL) with an IC50 value of 24.83 mg/mL for MCF-7 cell lines. The in-vitro antibacterial potential of ZMC NPs has been evaluated against four bacterial (Gram-positive and Gram-negative) strains and has demonstrated the highest inhibition zone (35 ± 0.03 mm) against the S. aureus strain and the lowest inhibition zone (31 ± 0.11) against the E. coli strain. Moreover, ZMC NPs have also shown strong molecular binding interactions with amino acids of estrogen receptor (ERα), S. aureus, and E. coli with binding energies of − 9.85, − 12.31, and − 6.04 kcal/mole, respectively.Graphical

Characterization and insight mechanism of an acid-adapted β-Glucosidase from Lactobacillus paracasei and its application in bioconversion of glycosides

Introduction: β-glucosidase is one class of pivotal glycosylhydrolase enzyme that can cleavage glucosidic bonds and transfer glycosyl group between the oxygen nucleophiles. Lactobacillus is the most abundant bacteria in the human gut. Identification and characterization of new β-glucosidases from Lactobacillus are meaningful for food or drug industry.Method: Herein, an acid-adapted β-glucosidase (LpBgla) was cloned and characterized from Lactobacillus paracasei. And the insight acid-adapted mechanism of LpBgla was investigated using molecular dynamics simulations.Results and Discussion: The recombinant LpBgla exhibited maximal activity at temperature of 30°C and pH 5.5, and the enzymatic activity was inhibited by Cu2+, Mn2+, Zn2+, Fe2+, Fe3+ and EDTA. The LpBgla showed a more stable structure, wider substrate-binding pocket and channel aisle, more hydrogen bonds and stronger molecular interaction with the substrate at pH 5.5 than pH 7.5. Five residues including Asp45, Leu60, Arg120, Lys153 and Arg164 might play a critical role in the acid-adapted mechanism of LpBgla. Moreover, LpBgla showed a broad substrate specificity and potential application in the bioconversion of glycosides, especially towards the arbutin. Our study greatly benefits for the development novel β-glucosidases from Lactobacillus, and for the biosynthesis of aglycones.

Experimental and density functional theory studies on some metal oxides and the derived nanoclusters: a comparative effects on human ferritin

A comprehensive investigation into the green synthesis of metal oxide nanoparticles (NPs) has garnered significant attention due to its commendable reliability, sustainability, and environmentally friendly attributes. Green synthesis methods play a crucial role in mitigating the adverse effects associated with conventional approaches employed for nanostructure preparation. This research endeavors to examine the impact of ginger plant extract-assisted green synthesis of metal oxides NPs on the serum ferritin levels of anemic diabetic patients in vitro, focusing specifically on α-Fe2O3 and ZnO NPs. Sixty diabetic volunteers with anemia (35–50 years) and thirty healthy volunteers were enrolled as controls. The assessment was conducted using the VIDAS Ferritin (FER) assay. Photoluminescence (PL) spectroscopy measurements were performed to elucidate the intrinsic and extrinsic transitions of these NPs, affirming the successful formation of α-structured iron oxide. Density functional theory (DFT) calculations were carried out at the B3LYP/6-311++G(d,2p) level of theory to investigate the geometry optimization and molecular electrostatic potential maps of the NPs. Furthermore, TD-DFT calculations were employed to explore their frontier molecular orbitals and various quantum chemical parameters. The binding affinity and interaction types of ZnO and α-Fe2O3 NPs to the active site of the human H-Chain Ferritin (PDB ID: 2FHA) target were determined with the help of molecular docking. Results unveiled the crystalline structure of ZnO and the α-structure of α-Fe2O3. Analysis of the frontier molecular orbitals and dipole moment values demonstrated that ZnO (total dipole moment (D) = 5.80 µ) exhibited superior chemical reactivity, biological activity, and stronger molecular interactions with diverse force fields compared to α-Fe2O3 (D = 2.65 µ). Molecular docking of the metal oxides NPs with human H-chain ferritin provided evidence of robust hydrogen bond interactions and metal-acceptor bonds between the metal oxides and the target protein. This finding could have a great impact on using metal oxides NPs-ferritin as a therapeutic protein, however, further studies on their toxicity are required.Graphical abstract

Triple-Mechanism Enhanced Flexible SiO2 Nanofiber Composite Hydrogel with High Stiffness and Toughness for Cartilaginous Ligaments.

Hydrogels are widely used in tissue engineering, soft robotics and wearable electronics. However, it is difficult to achieve both the required toughness and stiffness, which severely hampers their application as load-bearing materials. This study presents a strategy to develop a hard and tough composite hydrogel. Herein, flexible SiO2 nanofibers (SNF) are dispersed homogeneously in a polyvinyl alcohol (PVA) matrix using the synergistic effect of freeze-drying and annealing through the phase separation, the modulation of macromolecular chain movement and the promotion of macromolecular crystallization. When the stress is applied, the strong molecular interaction between PVA and SNF effectively disperses the load damage to the substrate. Freeze-dried and annealed-flexible SiO2 nanofibers/polyvinyl alcohol (FDA-SNF/PVA) reaches a preferred balance between enhanced stiffness (13.71 ± 0.28MPa) and toughness (9.9 ± 0.4MJ m-3). Besides, FDA-SNF/PVA hydrogel has a high tensile strength of 7.84 ± 0.10MPa, super elasticity (no plastic deformation under 100 cycles of stretching), fast deformation recovery ability and excellent mechanical properties that are superior to the other tough PVA hydrogels, providing an effective way to optimize the mechanical properties of hydrogels for potential applications in artificial tendons and ligaments.

Solubility of fructose and sucrose in mixtures of methanol and water: Experiment and application of equations of state and activity coefficient model

Beyond biochemical functions, carbohydrates have great industrial and economic importance. To improve industrial processes and to develop new applications for these substances, the knowledge of their solubility behavior in different solutions is often necessary. Therefore, the purpose of this work was to collect experimental data on the solubility of fructose and sucrose in hydroalcoholic solutions of methanol and water, using a chromatographic method. The solubility was evaluated for the entire mole fractions of the binary mixture covering the temperatures from 298.15 K to 323.15 K. The results indicated that the chromatographic method is suitable for determining sugar concentration, but it implies an increased uncertainty over the results. The solubility of both sugars was low in methanol-rich binary mixtures, rising with the increasing proportion of water. Greater dependence of the solubility as a function of the composition of the binary mixture was observed for sucrose, indicating stronger molecular interaction and therefore greater deviation from ideality. The NRTL activity coefficient model and the PC-SAFT and CPA equations of state were successfully employed to correlate the solid-liquid equilibrium. The binary interaction parameters were optimized as a function of temperature. The NRTL model has shown greater deviations than those presented by the equations of state. Meanwhile, the equations of state have presented a similar performance.

3,4-Dimethoxy phenyl thiosemicarbazone as an effective corrosion inhibitor of copper under acidic solution: comprehensive experimental, characterization and theoretical investigations.

This study investigates the corrosion inhibition potential of 3,4-dimethoxy phenyl thiosemicarbazone (DMPTS) for copper in 1 M hydrochloric acid (HCl) solutions, aiming to disclose the mechanism behind its protective action. Through an integrative methodology encompassing electrochemical analyses-such as weight loss measurements, potentiodynamic polarization, and electrochemical impedance spectroscopy (EIS)-we quantitatively evaluate the corrosion protection efficacy of DMPTS. It was determined that the optimal concentration of DMPTS markedly boosts the corrosion resistance of copper, achieving an impressive inhibition efficiency of up to 89% at 400 ppm. The formation of a protective layer on the copper surface, a critical aspect of DMPTS's inhibitory action, was characterized using Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). These techniques provided empirical evidence of surface morphology modifications and roughness changes, affirming the formation of a protective barrier against corrosion. A significant advancement in our study was the application of Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy, which identified chemical adsorption as the definitive mechanism of corrosion inhibition by DMPTS. The ATR-FTIR results explicitly demonstrated the specific interactions between DMPTS molecules and the copper surface, indicative of a robust protective adsorbed layer formation. This mechanistic insight, crucial to understanding the inhibitory process, aligns with the protective efficacy observed in electrochemical and surface analyses. Theoretical support, provided by the Quantum Theory of Atoms in Molecules (QTAIM) and quantum chemical computations, further validated the strong molecular interaction between DMPTS and copper, corroborating the experimental findings. Collectively, this research not only confirms the superior corrosion inhibition performance of DMPTS in an acidic setting but also elucidates the chemical adsorption mechanism as the foundation of its action, offering valuable insights for the development of effective corrosion inhibitors in industrial applications.

Unveiling the immunomodulatory mechanisms of pineapple metabolites: A multi-modal computational analysis using network pharmacology, molecular docking, and molecular dynamics simulation

The exploration of the immunomodulatory potential of pineapple metabolites holds promise for substantial implications across several fields, encompassing medicine, pharmacology, nutrition, and public health. This study explores potential immune-regulating properties of secondary pineapple metabolites beyond bromelain, using computational techniques. Pineapple juice's secondary metabolites were identified via LC-MS-based metabolomics, selected using KNApSAcK Kanaya and Dr. Duke's databases. A heatmap was generated with Orange v.3.27.0. Bioactivity predictions utilized the PASS Online webserver, while ADMET properties were forecasted. Network pharmacology explored metabolite interactions with protein targets. Molecular docking focused on compounds against receptors, choosing robust interactors for dynamic simulations. Our findings revealed that certain metabolites from pineapple juice/fermented juice exhibited interactions with proteins associated with pro-inflammatory cytokines. Specifically, the molecular docking results indicated that the carbohydrate moiety of bromelain (CMB) interacted strongly with TLR2, while 9,10-Dihydroxystearic acid showed strong interactions with NLRP3 (inflammasome). The flexibility and stability of these complexes were further assessed through molecular dynamics simulations conducted over a 50-ns time period. The MM-PBSA calculations also indicated low binding free energies between these complexes, suggesting strong molecular interactions. These findings suggest that CMB may interact with TLR2 and 9,10-Dihydroxystearic acid may interact with NLRP3, highlighting their potential as immunomodulatory agents. However, further experimental studies are warranted to confirm the therapeutic efficacy of these molecules and investigate their mechanisms of action in vivo.

IN SILICO ASSESSMENT OF AMELIORATIVE EFFECTS OF POLYUNSATURATED FATTY ACID (PUFAS) FROM NAVICULA SALINICOLA AS AN INHIBITOR OF BENIGN PROSTATE HYPERPLASIA

Objective: Benign prostatic hyperplasia (BPH) is a prevalent, non-cancerous condition affecting aging men worldwide. As an alternative approach to conventional treatment options, polyunsaturated fatty acids (PUFAs) have gained attention for their potential therapeutic effects on various health conditions. This study investigated the interaction of PUFAs obtained from Navicula salinicola with the macromolecule associated with BPH, represented by STAT3, that is involved in the androgen signaling pathway in BPH (PDB ID 6NJS), using molecular docking simulations.
 Methods: The docking simulations revealed the interaction patterns and binding affinities of 14 PUFAs with the amino acid residues of STAT3. The calculated binding energies and inhibition constants provided insights into the potential inhibitory effects of PUFAs on BPH.
 Results: Results indicated that g-linolenic acid exhibited a strong binding affinity, forming hydrogen bonds with ARG609 and hydrophobic interactions with VAL637 and PRO639, highlighting its potential as a potent inhibitor. Docosahexaenoic acid also showed favorable interactions with ARG609 and hydrophobic residues, suggesting its potential therapeutic relevance.
 Conclusion: g-Linolenic acid from N. salinicola exhibited a strong molecular interaction with STAT3.

Anti-Tuberculosis Potential of OJT008 against Active and Multi-Drug-Resistant Mycobacterium Tuberculosis: In Silico and In Vitro Inhibition of Methionine Aminopeptidase.

Despite the recent progress in the diagnosis of tuberculosis (TB), the chemotherapeutic management of TB continues to be challenging. Mycobacterium tuberculosis (Mtb), the etiological agent of TB, is classified as the 13th leading cause of death globally. In addition, 450,000 people were reported to develop multi-drug-resistant TB globally. The current project focuses on targeting methionine aminopeptidase (MetAP), an essential protein for the viability of Mtb. MetAP is a metalloprotease that catalyzes the excision of the N-terminal methionine (NME) during protein synthesis, allowing the enzyme to be an auspicious target for the development of novel therapeutic agents for the treatment of TB. Mtb possesses two MetAP1 isoforms, MtMetAP1a and MtMetAP1c, which are vital for Mtb viability and, hence, a promising chemotherapeutic target for Mtb therapy. In this study, we cloned and overexpressed recombinant MtMetAP1c. We investigated the in vitro inhibitory effect of the novel MetAP inhibitor, OJT008, on the cobalt ion- and nickel ion-activated MtMetAP1c, and the mechanism of action was elucidated through an in silico approach. The compound's potency against replicating and multi-drug-resistant (MDR) Mtb strains was also investigated. The induction of the overexpressed recombinant MtMetAP1c was optimized at 8 h with a final concentration of 1 mM Isopropyl β-D-1-thiogalactopyranoside. The average yield from 1 L of Escherichia coli culture for MtMetAP1c was 4.65 mg. A preliminary MtMetAP1c metal dependency screen showed optimum activation with nickel and cobalt ions occurred at 100 µM. The half-maximal inhibitory concentration (IC50) values of OJT008 against MtMetAP1c activated with CoCl2 and NiCl2 were 11 µM and 40 µM, respectively. The in silico study showed OJT008 strongly binds to both metal-activated MtMetAP1c, as evidenced by strong molecular interactions and a higher binding score, thereby corroborating our result. This in silico study validated the pharmacophore's metal specificity. The potency of OJT008 against both active and MDR Mtb was <0.063 µg/mL. Our study reports OJT008 as an inhibitor of MtMetAP1c, which is potent at low micromolar concentrations against both active susceptible and MDR Mtb. These results suggest OJT008 is a potential lead compound for the development of novel small molecules for the therapeutic management of TB.

Utilizing Drug Amorphous Solid Dispersions for the Preparation of Dronedarone per os Formulations

Dronedarone (DRN), an antiarrhythmic drug, exhibits potent pharmacological effects in the management of cardiac arrhythmias. Despite its therapeutic potential, DRN faces formulation challenges due to its low aqueous solubility. Hence, the present study is dedicated to the examination of amorphous solid dispersions (ASDs) as a strategic approach for enhancing the solubility of DRN. Initially, the glass forming ability (GFA) of API was assessed alongside its thermal degradation profile, and it was revealed that DRN is a stable glass former (GFA III compound) that remains thermally stable up to approximately 200 °C. Subsequently, five commonly used ASD matrix/carriers, i.e., hydroxypropyl methylcellulose (HPMC), povidone (PVP), copovidone (PVP/VA), Soluplus® (SOL), and Eudragit® E PO (EPO), were screened for the formation of a DRN-based ASD using film casting and solvent shift methods, along with miscibility evaluation measurements. SOL proved to be the most promising matrix/carrier among the others, and, hence, was used to prepare DRN ASDs via the melt-quench method. The physicochemical characterization of the prepared systems (via pXRD) revealed the complete amorphization of the API within the matrix/carrier, while the system was physically stable for at least three months after its preparation. In vitro release studies for the ASDs, conducted under non-sink conditions, revealed the sustained supersaturation of the drug for at least 8 h. Finally, the use of attenuated total reflectance (ATR) FTIR spectroscopy showed the formation of a strong molecular interaction between the drug molecules and SOL.

A-A Strategy Enables Desirable Performance of All-Polymer Solar Cells Fabricated with Nonhalogenated Solvents.

Most polymer acceptors have been designed by applying a D (electron-rich unit)-A (electron-deficient unit) strategy, which are principally processed with halogenated solvents to fabricate all-polymer solar cells (all-PSCs). Two novel polymer acceptors, containing an A-A type backbone, were designed and synthesized, which can be readily dissolved in o-xylene. The polymer PY-FBTA, comprising a Y6 derivative as the first A unit and a benzotriazole derivative as the second A unit, shows smaller dihedral angles in the backbone, stronger molecular interactions, higher LUMO level, more complementary absorption spectrum, and better morphology with PM6 than the polymer PY-DPP comprising a diketopyrrolopyrrole derivative as the second A unit. Accordingly, the PM6:PY-FBTA all-PSC achieves a higher PCE of 13.95% than the all-PSC based on PM6:PY-DPP (9.51%) for thoroughly improved Jsc (22.34 mA cm-2), Voc (0.963 V), and FF (64.84%) values, which are fabricated with o-xylene as the solvent. This work demonstrates that the A-A structure is a desirable strategy for designing polymer acceptors for efficient all-PSCs prepared with nonhalogenated solvents.

Preparation and structural characterization of pullulan and whey protein isolate-based electrospun nanofiber

The impact of blended ratios was analyzed on the development and characterization of electrospun fibers using various combinations of pullulan (PUL) and whey protein isolate (WPI). The physical parameters like apparent viscosity, electrical conductivity and surface tension of blended solutions were improved after the addition of PUL in the blends, resulting in a uniform electrospun nanofiber. Scanning electron microscope (SEM) of nanofibers revealed bead-free, smooth and uniform structural conformation. Whereas, the uniformity of nanofiber was compromised by using higher concentrations of WPI in the blend. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD) and Thermogravimetry analysis further confirmed the strong molecular interaction between polysaccharide and protein. The incorporation of WPI in PUL based electrospun nanofibers enhanced hydrophobicity, potentially facilitating the delivery of bioactive compounds. The WPI and PUL:WPI-based nanofibers demonstrated robust antioxidant potential, due to the presence of total phenolic contents (TPC). The stability of PUL interaction with WPI (β-lactoglobulin and α-lactalbumin) was confirmed through hydro-carbon (C–H) and hydrogen bond interactions by molecular docking. Finally, we can conclude that polysaccharide and protein-based nanofiber can be used to deliver bioactive compounds in food and pharmaceutical industries.