Structural Modifications Research Articles

Design, synthesis, in vitro and in silico studies of novel piperidine derived thiosemicarbazones as inhibitors of dihydrofolate reductase.

Dihydrofolate reductase (DHFR), an essential enzyme in folate metabolism, presents a promising target for drug development against various diseases, including cancer and tuberculosis. Herein, we present an integrated approach combining in vitro biochemical assays with in silico molecular docking analysis to evaluate the inhibitory potential of 4-piperidine-based thiosemicarbazones 5(a-s) against DHFR. In our in vitro study, a novel series of 4-piperidine-based thiosemicarbazones 5(a-s) were assessed for their inhibitory activity against DHFR enzyme. The synthesized compounds 5(a-s) exhibited potent inhibition with IC50 values in the range of 13.70 ± 0.25 µM to 47.30 ± 0.86 µM. Among all the derivatives 5p displayed highest inhibitory activity. Simultaneously, in silico analysis were performed and compared with standard drug (Methotrexate) to predict the binding affinity and interaction pattern of synthesized compounds with DHFR active site. SAR analysis was done to elucidate how structural modifications impact compound's biological activity, guiding the rational design of potent and selective drug candidates for targeted diseases. These findings may provide a comprehensive assessment of 4-piperdine-based thiosemicarbazones as DHFR inhibitors and contribute to the development of novel therapeutics targeting DHFR-associated diseases.

QSAR Modeling, Molecular Docking and ADMET Study of Aryl Fluorosulfate Derivatives as Potential Anti-TB Agents

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, stands as a global infectious disease presenting substantial public health challenges due to its high incidence and mortality rates. The prolonged use of conventional anti-TB therapies has led to the emergence of severe drug resistance in Mtb, resulting in extended treatment durations, increased costs, poor patient compliance, and reduced cure rates. This phenomenon has posed a significant burden on global TB prevention and control efforts, necessitating a shift in research focus toward the exploration of novel anti-TB drugs. In this context, utilizing QSAR modeling methods, our study systematically investigated the relationship between the chemical structures of 36 aryl fluorosulfate derivatives and their inhibitory activity against Mtb. Robust and predictive Topomer CoMFA and HQSAR models were developed, featuring Topomer CoMFA model parameters: q 2 = 0.659, r 2 = 0.969, F = 102.877, N = 6, SEE = 0.138; HQSAR model parameters: q 2 = 0.705, r 2 = 0.873, SEE = 0.264, HL = 199, N = 4. Leveraging these models, structural modifications were applied to the compounds using the ZINC15 database, leading to the successful design and screening of three novel compounds with desirable inhibitory activity. Molecular docking and ADMET performance prediction results indicated that these three new compounds exhibit strong binding capabilities and promising pharmaceutical potential. This study provides valuable insights and research directions for the development of aryl fluorosulfate derivatives as potential agents for tuberculosis treatment and as novel drugs.

Microstructure-thermal transport property correlation after cold/cryo rolling deformation of alloy D9

ABSTRACT Plastic deformation alters the microstructure of a material due to the formation of twins, high density of dislocations and strain-induced phases and grain refinement. Such microstructural modifications can affect thermal transport properties of a material. In this work, variation in thermal diffusivity (TD) was investigated in cold worked (CW) and cryo rolled (CR) alloy D9 (ASTM designation A771/UNS S38660), using laser flash analyser after 20–80% thickness reduction. Deformed samples were characterised using XRD and microscopy techniques for structure and microstructure modifications besides correlating with the change in hardness. Temperature dependence of thermal diffusivity was measured from room temperature up to 1273 K. Microstructural features confirmed the formation of deformation-induced martensite in CR specimen. This was accompanied by up to 172% increase in hardness in 80% CR compared to annealed specimen. The dislocation density estimated from XRD structural profile showed an increase with the percentage of deformation. For all specimens, thermal diffusivity showed an increasing trend with temperature but decreased with deformation. The reduction in thermal diffusivity was non-negligible beyond 40% thickness reduction for all deformed specimen and was substantial specifically for CR alloy D9.

Exploring the impact of structural modification of double perovskite composite cathode material on oxygen reduction reaction in intermediate temperature solid oxide fuel cell

Exploring the impact of structural modification of double perovskite composite cathode material on oxygen reduction reaction in intermediate temperature solid oxide fuel cell

Effect of Bi2O3 in Bi2O3-SrO-ZnO-B2O3 glass: structural, mechanical, optical, and gamma ray shielding modifications

The effect of Bi2O3 in Bi2O3-SrO-ZnO-B2O3 glasses has been evaluated in this study. The density of the glasses increased from 5.127 g/cm³ to 6.214 g/cm³ as Bi2O3 concentration increased from 35% to 50%. The rise in molar mass and molar volumes points towards the opening of the network. The structural modifications increased the elastic moduli from 30.110 to 30.944 GPa for Young modulus; 17.653 to 17.860 GPa for bulk modulus; 13.242 to 13.662 GPa for shear modulus and 35.309 to 36.077 GPa for longitudinal modulus, respectively. The FTIR spectra indicate the conversion of BO4 to BO3 with increasing Bi2O3 concentration which accounts for the increase of the non-bridgingoxygens (NBOs). The band gap energy decreases from 3.165 to 3.020 eV with increasing Bi2O3 content. The transmission factors (TF) and other relevant parameters were evaluated for four different thicknesses of the glasses (0.5, 1, 1.4 and 2 cm). The 0.5 cm thick glass retained the highest TF when compared to other thicknesses. The TF for 0.5cm thick glass is about 70%, and drops to about 20% for 2 cm thickness, which confirms that at 2 cm thickness, the glass materials shield better than 0.5, 1 and 1.4 cm. Furthermore, the addition of Bi2O3 causes a decrease in TF, so the glass with a high Bi2O3 content shields gamma radiation better than those with a low Bi2O3 content. The half value layer (HVL) values reduce as the Bi2O3 content is increased at all examined energies, confirming that the glass sample with highest Bi2O3 content has the superior shielding capability compared to the remaining examine glasses.

Chirality-Mediated 1D-to-2D Phase Transition in Hybrid Lead Halide Perovskites.

Dimensionality engineering plays a pivotal role in optimizing the performance, ensuring long-term stability, and expanding the versatile applications of lead halide perovskites (LHPs). Currently, the manipulation of LHP dimensions primarily occurs during the synthesis stage, a procedure hampered by constraints, including synthetic complexity and irreversibility. This investigation successfully achieved a transition from one-dimensional (1D) to two-dimensional (2D) structures in chiral LHPs by applying hydrostatic pressure. Remarkably, this pressure-induced transition in dimensionality is absent in the racemic analogue due to the staggered arrangement of inorganic chains and the elevated steric hindrance posed by the organic cations. Notably, the hydrogen bonding between organic cations and the inorganic framework adopts a symmetrical arrangement in the racemic system but a helical configuration along the 1D chain direction in the chiral counterparts. This distinct helical arrangement induces a consequential distortion in the inorganic moiety, resulting in the emergence of a spin-polarized Rashba-Dresselhaus texture that explains the chirality's electronic spin origin. Furthermore, both experimental and density functional theory calculation results demonstrate that the 1D-to-2D phase transition in chiral halide perovskites can induce significant modifications in the electronic structures and associated optical emissions. In summary, the findings unveil novel avenues for manipulating optoelectronic properties in chiral perovskites through dimensionality engineering.

N-Alkylation of Amines for the Synthesis of Potential Antiviral Agents: A Structural Modification Approach

The threat of emerging viral outbreaks has increased the need for fast and effective development of therapeutics against emerging pathogens. One approach is to modify the structure of existing therapeutic agents to achieve the desired antiviral properties. Here, we attempted to synthesize a new antiviral compound by modifying the structure of chloroquine using the N-alkylation of the primary amine (N1,N1-diethylpentane-1,4-diamine) that is used in chloroquine synthesis. Chloroquine is commonly used to treat malaria. Like chloroquine, chloroquine is used for treating conditions such as rheumatoid arthritis, lupus, and malaria. For instance, in malaria treatment, it targets and inhibits the growth of the malaria parasite, aiding in its elimination from the body. The synthesized compounds MP1, C1, and TT1 were further tested in vitro against the B.1 lineage of SARS-CoV-2. One of the compounds, MP1, demonstrated minor effectiveness, with an IC50 of XX at only a high concentration (at a concentration of 60 μM) and decreased both the number of SARS-CoV-2 copies and the amount of infectious virus. Although the synthesized compounds failed to markedly inhibit SARS-CoV-2, this could be a pontial mechanism for manipulating the drug structure against other pathogens. MP1, TT1, C1, and chloroquine diphosphate were used as ligands for molecular docking to determine the principal interactions between these compounds and the active site of the protein downloaded from the Protein Data Bank (PDB ID: 6lzg). Finally, ADMET assays were performed on the synthesized compounds to determine their pharmacokinetics and bioavailability.

Insights into the Structural Modification of Selenium-Doped Derivatives with Narrowband Emissions: A Theory Study

Insights into the Structural Modification of Selenium-Doped Derivatives with Narrowband Emissions: A Theory Study

Advancements in calixarene-protected titanium-oxo clusters: from structural assembly to catalytic functionality.

This review explores calixarenes, a prominent family of third-generation supramolecules celebrated for their distinct hollow, cavity-shaped structures. These macrocycles are intricately assembled by linking multiple phenolic units orthogonally through methylene (-CH2-), sulfur (-S-), or sulfonyl (-SO2-) bridges. This structural framework plays a pivotal role in the intricate assembly of nanoclusters, significantly advancing the field of cluster chemistry. A key focus of current research is the remarkable ability of calixarenes to stabilize titanium-oxo clusters. Our review details the application of calixarenes in constructing titanium-oxo cluster structures, emphasizing how these clusters, when encapsulated within calixarenes, exploit flexible coordination sites for structural modifications and serve as foundational units for more complex assemblies. Additionally, we investigate how these calixarene-stabilized metal-oxo clusters function as versatile scaffolds for catalytically active metal ions, facilitating the creation of bimetallic nanoclusters. These clusters not only exhibit unique structural diversity but also demonstrate exceptional catalytic efficiency. This review aims to inspire ongoing exploration and innovation in the use of calixarenes for the synthesis and application of advanced cluster materials.

Absorption of Polypropylene in Dipalmitoylphosphatidylcholine Membranes: The Role of Molecular Weight and Initial Configuration of Polymer Chains.

We study by molecular dynamics simulations the absorption of polypropylene (PP) chains within a dipalmitoylphosphatidylcholine (DPPC) lipid membrane in aqueous solvent. DPPC represents the most abundant phospholipid in biological membranes, while PP is one of the most common synthetic polymers diffused in the anthropic environment. By following in detail the absorption process, and the corresponding structural modification undergone by the membrane, we show how the initial configuration and the PP molecular weight determine the overall behavior of the system. Specifically, if PP chains initially lie on the DPPC surface, they are fully absorbed; likewise, polymers initially included within the membrane cannot escape from. On the other hand, if polymers are placed sufficiently apart from the membrane, they have time to join together and coalesce into a few nanoparticles. At contact, such nanoparticles may completely dissolve (for low molecular weight) and then be absorbed. For high molecular weight, not all of them dissolve, and therefore the system attains a condition in which some of the chains are absorbed, while others form a residual nanoparticle staying outside (but in contact with) the membrane. Such a state─albeit energetically unfavorable with respect to a condition in which all PP chains are absorbed─remains stable, at the least over a substantial simulation time, extending in our study up to 1.6 μs. The tendency for polymers to spontaneously form aggregates, which then prefer to stay in contact with the membrane, is further corroborated by calculation of the DPPC-nanoparticle potential of mean force.

New methyl compounds using the predicted data mining approach (PDMA), coupled with the biotransformation of Streptomyces peucetius O-methyltransferase

The structural modification of natural products using biotransformation is an effective way to produce organic compounds in a regioselective and/or stereoselective manner. O-methylation is a major modification in nature. The predicted data mining approach (PDMA) can efficiently screen out biotransformable precursor candidates to produce new (functional) compounds from thousands of derivatives. Herein, an O-methyltransferase (SpOMT2884) from Streptomyces peucetius (ATCC 27952 strain) was selected to biotransform eight precursors, screened from 4364 commercially available natural compounds via PDMA. Seven of the eight precursors (calceolarioside B, isomangiferin, mangiferin, methyl chlorogenate, plantagoside, protosappanin B, and wedelolactone) could be biotransformed from SpOMT2884. Fourteen biotransformed compounds were confirmed to be methyl products with a high-resolution mass analysis. Three methyl products from two precursors (plantagoside and protosappanin B) were selected for further production and identified using nucleic magnetic resonance spectral methods. One methyl product of protosappanin B was identified as 10-O-methyl protosappanin B (1), which gained potent anti-inflammatory activity (IC50 = 76.1 ± 4.7 μM) compared with its precursor, protosappanin B (IC50 = 157.7 ± 5.0 μM). In a case study, two methyl products of plantagoside were indeed identified as novel 4′-O-methyl plantagoside (3) and 5′-O-methyl plantagoside (4). This study demonstrates that PDMA is a good in silico approach for screening biotransformable precursor candidates for the in vitro production of new or bioactive compounds from numerous natural products.

Visible-light-driven F/C co-doping g-C3N4 nanosheets for efficient hydrogen evolution: Charge redistribution on C4 delocalized large π bond

Developing photocatalytic hydrogen evolution technology based on graphitic carbon nitride (g-C3N4, CN) has emerged as a potential solution for the future energy shortage in recent years. Herein, carbon (C) and fluorine (F) co-doping graphitic carbon nitride nanosheets (CFCN) were synthesized via a one-pot co-thermal method without introducing any metal element. Exceptional hydrogen production activity (3.87 mmol/h/g) was achieved by CFCN under visible light irradiation, which was 4.2-fold increase compared to the pristine CN. It could be attributed to the large specific surface area (51.59 m2/g) and efficient mass transfer facilitated by the porous sheet-like morphology of CFCN. Additionally, the modification of the band structure and internal charge redistribution were investigated via density functional theory (DFT) calculations, which confirmed there was a unidirectional and fast electron transfer channel from N through the C4 delocalized large π bond to F. This creative research uncovered the pivotal role of F/C co-doping in enhancing photocatalytic hydrogen evolution efficacy, offering cutting-edge insights into the design of sustainable and eco-friendly photocatalysts based on metal-free CN.

Impact of Chromatin Organization and Epigenetics on CRISPR-Cas and TALEN Genome Editing.

DNA lies at the heart of the central dogma of life. Altering DNA can modify the flow of information in fundamental cellular processes such as transcription and translation. The ability to precisely manipulate DNA has led to remarkable advances in treating incurable human genetic ailments and has changed the landscape of biological research. Genome editors such as CRISPR-Cas nucleases and TALENs have become ubiquitous tools in basic and applied biological research and have been translated to the clinic to treat patients. The specificity and modularity of these genome editors have made it possible to efficiently engineer genomic DNA; however, underlying principles governing editing outcomes in eukaryotes are still being uncovered. Editing efficiency can vary from cell type to cell type for the same DNA target sequence, necessitating de novo design and validation efforts. Chromatin structure and epigenetic modifications have been shown to affect the activity of genome editors because of the role they play in hierarchical organization of the underlying DNA. Understanding the nuclear search mechanism of genome editors and their molecular interactions with higher order chromatin will lead to improved models for predicting precise genome editing outcomes. Insights from such studies will unlock the entire genome to be engineered for the creation of novel therapies to treat critical illnesses.

Nanoscale Operando Imaging of Electrically Driven Charge-Density Wave Phase Transitions.

Structural transformations in strongly correlated materials promise efficient and fast control of materials' properties via electrical or optical stimulation. The desired functionality of devices operating based on phase transitions, however, will also be influenced by nanoscale heterogeneity. Experimentally characterizing the relationship between microstructure and phase switching remains challenging, as nanometer resolution and high sensitivity to subtle structural modifications are required. Here, we demonstrate nanoimaging of a current-induced phase transformation in the charge-density wave (CDW) material 1T-TaS2. Combining electrical characterizations with tailored contrast enhancement, we correlate macroscopic resistance changes with the nanoscale nucleation and growth of CDW phase domains. In particular, we locally determine the transformation barrier in the presence of dislocations and strain, underlining their non-negligible impact on future functional devices. Thereby, our results demonstrate the merit of tailored contrast enhancement and beam shaping for advanced operando microscopy of quantum materials and devices.

Study on the Influence of Host–Guest Structure and Polymer Introduction on the Afterglow Properties of Doped Crystals

Due to their low cost, good biocompatibility, and ease of structural modification, organic long-persistent luminescence (LPL) materials have garnered significant attention in organic light-emitting diodes, biological imaging, information encryption, and chemical sensing. Efficient charge separation and carrier migration by the host–guest structure or using polymers and crystal to build rigid environments are effective ways of preparing high-performance materials with long-lasting afterglow. In this study, four types of crystalline materials (MODPA: DDF-O, MODPA: DDF-CHO, MODPA: DDF-Br, and MODPA: DDF-TRC) were prepared by a convenient host–guest doping method at room temperature under ambient conditions, i.e., in the presence of oxygen. The first three types exhibited long-lived charge-separated (CS) states and achieved visible LPL emissions with durations over 7, 4, and 2 s, respectively. More surprisingly, for the DDF-O material prepared with PMMA as the polymer substrate, the afterglow time of DDF-O: PMMA was longer than 10 s. The persistent room-temperature phosphorescence effect caused by different CS state generation efficiencies and rigid environment were the main reason for the difference in LPL duration. The fourth crystalline material was without charge separation and exhibited no LPL because it was not a D-A system. The research results indicate that the CS state generation efficiency and a rigid environment are the key factors affecting the LPL properties. This work provides new understandings in designing organic LPL materials.

Unveiling the therapeutic significance of shikimate pathway-derived phenolic acids against penicillin-binding protein 3 of Pseudomonas aeruginosa

ABSTRACT This study investigated the modulatory potential of Shikimate pathway-derived phenolic acids against penicillin-binding protein 3 (PBP3) of Pseudomonas aeruginosa using computational and in vitro methods. The binding and inhibitory capabilities of 22 phenolic acids against the catalytic site of PBP3 were evaluated and revealed ellagic and chlorogenic acids as the top inhibitors, showing superior docking scores of −8.4 kcal/mol each compared to the standard, cefotaxime (−7.5 kcal/mol). Dynamics simulation of their PBP3 complexes indicated chlorogenic acid’s efficacy in inhibiting PBP3 (−33.65 kcal/mol) relative to cefotaxime (−30.10 kcal/mol), while interacting with key catalytically relevant residues. The quantum features analysis using DFT/B3LYP suggested chlorogenic acid’s superior reactivity and compatibility with the PBP3 active site. In vitro evaluation revealed an MIC of 200 mg/ml for chlorogenic acid and 0.8 mg/ml for cefotaxime against Pseudomonas aeruginosa ATCC 27,853, while their combination showed a synergistic action mechanism (FIC index of 0.5). These observations were validated in time-kill kinetics (gradual decrease in viable cells over 24 h). The study concludes chlorogenic acid as promising PBP3 inhibitor. Nonetheless, further studies could focus on the structural modification of chlorogenic acid to improve its pharmacokinetic properties and potential as an antibacterial drug candidate in vivo.

Response of Lanthanide Sesquioxides to High‐Energy Ball Milling

Sesquioxides (M2O3) exhibit rich polymorphism with distinct phases that form over broad compositional, pressure, and temperature ranges. This makes these materials an ideal model system for studying the effects of high‐energy ball milling and the far‐from‐equilibrium conditions induced by complex mechanical interactions. Polycrystalline bixbyite‐structured binary sesquioxides (M2O3, M = Gd, Dy, Ho, Er, Yb, and Y) were processed by high‐energy ball milling and the resulting structural modifications were characterized by synchrotron X‐ray diffraction. Ball milling drives the initial cubic structure (“C‐type”) in each oxide to the monoclinic, “B‐type” structure, with the rate of formation and maximum attainable phase fraction dependent on the cation size. The B‐type phase fraction increases with milling time for each sesquioxide, but reaches steady‐state behavior below unity, which contrasts with previous studies that induced a complete transformation by exposure to temperature, pressure, or ion radiation. This behavior suggests a complex interaction regime within a planetary ball mill characterized by transient processes, which exert simultaneous 1) driving forces to form the B‐type phase and 2) kinetic pathways to partially recover the C‐type phase. We show that these two processes are correlated with the effects of pressure and temperature during mechanical interactions between the sample and milling tools.

Photocatalytic degradation of methylene blue in aqueous media using magnesium-substituted copper ferrite as a magnetic catalyst

In this study, copper nanosized ferrites substituted with magnesium ions were synthesized using the sol-gel self-combustion method, with polyethylene glycol (MW 2000) serving as both fuel and chelating agent. Structural properties were investigated using X-ray diffraction. It was confirmed that all samples crystallized as cubic spinels with space group Fd3m. Optical studies showed band gaps increasing from 1.51 eV for CuFe2O4 to 1.62 eV for MgFe2O4, suggesting modifications in electronic structure due to magnesium substitution. Photocatalytic studies revealed that CuFe2O4 exhibited the most efficient degradation of Methylene Blue dye, with near-complete degradation at 160 minutes. Magnesium-substituted samples (x = 0.4 and x = 0.6) also showed significant degradation, though at a slower rate compared to pure CuFe2O4. Photocatalytic performance, particularly in degrading Methylene Blue, was evaluated using various kinetic models such as First- and Second-Order Kinetics, the Langmuir-Hinshelwood model, and the two-parameter Weibull distribution.

Structural insight into the lead identification of a dual inhibitor of PDE1B and PDE10A: Integrating pharmacophore-based virtual screening, molecular docking, and structure-activity-relationship approaches

Schizophrenia is a chronic neuropsychiatric disorder affecting more than 1% of the world's population. Current antipsychotic treatments show inadequacy in mitigating the negative and cognitive symptoms of schizophrenia. In addition, these medications cause undesirable extrapyramidal side effects. According to the studies, inhibition of phosphodiesterase (PDE) 1B and PDE10A simultaneously can alleviate positive, negative, and cognitive symptoms of schizophrenia. Thus, this study aims to identify new dual inhibitors of PDE1B and PDE10A using ligand-based pharmacophore modelling, virtual screening, and molecular docking studies. Accordingly, the generated pharmacophore models of PDE1B and PDE10A comprised hydrogen bond acceptor, aromatic ring, and hydrophobic features. These features were essential for retrieving the active hits from the Universal Natural Product Database in the virtual screening. Additional filters were subsequently employed to identify potential hits that could be developed into central nervous system-active compounds. Hits meeting all the screening criteria were subjected to docking studies with PDE1B and PDE10A. Among these hits, UNPD167314 exhibited significant binding affinities for the target receptors. It occupied the P-clamp and displayed hydrophobic, aromatic, and hydrogen bond interactions with the active site residues of both receptors, thus selected as a lead compound for the design of potent and selective dual inhibitors. The structural modifications of UNPD167314 resulted in the design of 35 novel inhibitors. Out of 35, four compounds exhibited high and comparable binding affinities for both PDE1B and PDE10A, making them promising candidates for further evaluation and optimisation.

Effect of Mo on surface reconstruction of FeCoNi-based high entropy alloy film electrode for oxygen evolution reaction

The selection of elements, tune of compounds types and modification of structure are important ways to improve OER activity of high-entropy alloys. The reconstruction behavior of film electrodes during OER process revealed that Mo element has a strong promoting effect on the reconstruction of FeCoNi-based films. It is shown by first-principles that electron-deficient region could be formed near Mo, and electron-rich region could be formed near surrounding elements of Mo. Charge transfer may be the reason that Mo promotes reconstruction of high-entropy alloys. Compared with FeCoNiCr film electrode, FeCoNiCrMo film electrode, the 2p3/2 binding energy peaks of Fe/Co/Ni in which are shifted forward, has more oxygen-containing species and oxygen vacancies. The study also revealed the existence of lattice oxygen mechanism during OER process. The deposition thickness of alloy film has a linear relationship with sputtering time and deposition rate of FeCoNiCrMo. There is an optimal deposition thickness of FeCoNiCrMo film electrode for OER. FeCoNiCrMo film electrodes have the most excellent OER performance: the overpotential is 268 mV, and the Tafel slope is 57.6 mVdec−1.