This study proposes a novel polymeric membrane composed of sodium alginate incorporating silver nanoparticles (AgNPs) and green propolis extract (GPE), for potential wound dressing. Five formulations were developed: a control (MB, alginate/glycerol), one with GPE at 0.5 mg/mL (MBE), and three with increasing silver nitrate (AgNO3) concentrations of 1.0, 3.0, and 5.0 mM (MBE1, MBE3, and MBE5). AgNP formation was confirmed by a visible color shift from white to dark brown. Characterization via FT-IR, DSC, and TGA/DTG confirmed successful incorporation of GPE and AgNPs into the polymeric matrix, revealing molecular interactions and distinct thermal stability profiles across all membranes. Membrane thickness increased progressively (0.118-0.174 mm) with AgNP concentration. Water vapor permeability (WVP) improved upon adding GPE and AgNPs, peaking at 1.47 × 10- 3 g.mm/kPa·s·m2 for MBE3. Mechanically, AgNP-containing membranes exhibited greater flexibility, with strain values near 90% and Young's Modulus between 0.29-0.32 MPa. Wettability analysis showed increased hydrophilic character of AgNP membranes, with contact angles as low as 34.3°. Biocompatibility testing using the chorioallantoic membrane (CAM) assay confirmed non-irritating profile. Molecular docking of GPE's major compounds-drupanin, artepilin C, and 4,5-dicaffeoylquinic acid-further supports the therapeutic potential of these dressings for wound care applications.

Abstract A novel cocrystal composed of nicotinamide (NA) and undecanoic acid (UA) in a 1:1 stoichiometry has been successfully synthesized via slow evaporation and comprehensively characterized through a multidisciplinary approach combining experimental and computational methods. Single-crystal X-ray diffraction revealed that the NA–UA cocrystal crystallizes in the triclinic symmetry (P̅1) with two NA-UA formulas per unit cell (Z = 2). The supramolecular assembly is primarily stabilized by classical O–H···N hydrogen bonding between the carboxylic acid group of UA and the pyridine nitrogen of NA, complemented by N–H···O interactions involving the amide function. Hirshfeld surface analysis and 2D fingerprint plots quantitatively mapped the intermolecular interaction landscape, revealing that H···H (67.8%), H···O/O···H (17.2%), and H···C/C···H (6.5%) contacts dominate the crystal packing, with significant contributions from dispersive interactions along the aliphatic chain. Crystal void analysis demonstrated efficient molecular packing with a void volume of 108.27 Å (≈12% of the total unit cell volume). Vibrational analyses (Raman and Fourier transform infrared spectroscopy) confirmed the presence of both molecular components and identified characteristic shifts in hydrogen-bond functional groups. Density functional theory calculations confirmed the excellent agreement with experimental vibrational modes and validated the optimized crystal structure. In silico pharmacokinetics predictions indicated favorable pharmacokinetic properties, including high gastrointestinal absorption, compliance with Lipinski’s rule of five, and absence of cytochrome P450 inhibition, although the cocrystal exhibited nonpermeability across the blood–brain barrier. This work establishes the structural framework and physicochemical characteristics of a new NA–UA cocrystal, providing fundamental insights into the interplay between hydrogen bonding and dispersive forces in drug-coformer assemblies and contributing to the rational design of pharmaceutical cocrystals with tailored properties.

Copper complexes are known for a range of biological properties that include anticancer, antimicrobial, and superoxide dismutase-like activities. In this work, we describe the synthesis of [Cu(phen)(L-arg)Cl]Cl·2.5H2O crystal, formed by the complexation of the metallic ion copper(II) with organic ligands – 1,10-phenanthroline (phen) and L-arginine (L-arg) –, by slow solvent evaporation. The crystal was characterized by advanced spectroscopic and structural techniques, such as Powder X-ray Diffraction (PXRD), Fourier Transform - Infrared (FT-IR) and Raman Spectroscopy. Density functional theory (DFT) calculations were also carried out the first time for [Cu(phen)(L-arg)Cl]+ complex, considering vacuum conditions and the solvation effects in water and in methanol, showing a greater stability of the complex in water. The intramolecular IR and Raman modes were determined from the DFT calculations, while time-dependent DFT calculations supported the study of electronic transitions. Solvation effects on calculated IR and Raman spectra were also evaluated, and spectral changes were identified. Initial analyses of the interaction between the complex and double-stranded deoxyribonucleic acid (DNA) were performed, showing ability to interact via hydrogen bonds with a binding affinity of −8.0 kcal/mol. The anticancer activity of the synthesized crystal was tested on prostate (PC-3) and promyelocytic (HL-60) cancer cell lines, revealing cytotoxicity in both lines at 1.4 and 1.7 µM, respectively. The antibacterial activity of the crystal was also tested on Gram-positive (Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, Streptococcus mutans) and Gram-negative (Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa) bacterial strains, achieving satisfactory inhibition at the concentration of 50 µg/mL. The biological results suggest a high potential of [Cu(phen)(L-arg)Cl]Cl·2.5H2O to be exploited as a chemotherapeutic drug for the treatment of prostate cancer and leukemia, and also as antibacterial drug candidate.

Copper(II) complexes with aromatic N-heterocyclic ligands have attracted considerable attention as potential anticancer agents due to their capacity to interact with deoxyribonucleic acid and inhibit tumor cell proliferation. Despite the structural characterization of the binuclear [Cu(Bipyridine)(NO3)(OH)](2) complex, reported nearly three decades ago, its physicochemical and biological landscape remained largely unexplored. In the present work, a comprehensive characterization of this complex is described, encompassing experimental and computational approaches. The complex was synthesized by slow solvent evaporation and its structure was confirmed by powder X-ray diffraction (PXRD) and Rietveld refinement, which established a triclinic system (space group P1, Z = 1) with lattice parameters in good agreement with literature values (Delta V = 0.44%). Ultraviolet-visible spectroscopy revealed a d-d transition at 641 nm, from which a crystal field splitting parameter of 10Dq approximate to 15,601 cm(-1) was estimated, confirming the stronger ligand field of 2,2'-bipyridine relative to water. Density functional theory (DFT) calculations using the PBE1PBE functional in vacuum, water, and methanol revealed the triplet state as the most stable configuration and demonstrated a solvation-dependent increase in the HOMO-LUMO gap (3.40 eV in vacuum; 4.65 eV in water), reflecting enhanced electronic stability under physiological conditions. High electrophilicity values (pi = 5.05-5.51 eV) support the potential for interactions with biological nucleophiles. Hirshfeld surface analysis quantified the dominant intermolecular interactions in the crystal lattice, with H center dot center dot center dot O/O center dot center dot center dot H contacts accounting for 41.1% of the surface. A group-theorybased normal mode analysis provided suitable assignment of the observed modes, with strong agreement between experimental and DFT-calculated spectra. Thermal analysis demonstrated stability up to 473 K, confirmed by variable-temperature PXRD up to 620 K. Molecular docking revealed affinity for DNA (Ki = 6.27 mu M, PDB: 1BNA) and the breast cancer-associated 3 alpha-hydroxysteroid dehydrogenase type 3 enzyme (Ki = 36.69 mu M, PDB: 4XO6). In silico pharmacokinetics profiling indicated limited oral bioavailability due to high topological polar surface area (TPSA = 169.18 angstrom 2), though favorable water solubility (Log S = 0.31) and absence of CYP450 inhibition suggest low hepatotoxicity risk. Cytotoxicity assays yielded half-maximal inhibitory concentration (IC50) values of 39.73 mu M and 14.46 mu M against MCF-7 breast adenocarcinoma and GM07492A healthy fibroblast cell lines, respectively, with a selectivity index of 0.36. These results establish [Cu(Bipyridine)(NO3)(OH)](2) as a biologically relevant binuclear copper(II) complex whose tumor selectivity may be improved through targeted nanoencapsulation strategies.

A multicomponent system of theophylline (TH) with nitric acid (HNO3), designated as THNO3, was synthesized via slow evaporation from ethanolic solution and structurally characterized as a monohydrate cocrystal salt. Single crystal X-ray diffraction revealed a triclinic system (P1-space group) comprising one neutral TH molecule, one theophyllinium cation (TH+), one nitrate ion (NO3 -), and one water (H2O) molecule per asymmetric unit. Hirshfeld surface analysis indicated dominant H & centerdot;& centerdot;& centerdot;H (34.4%) and O & centerdot;& centerdot;& centerdot;H/H & centerdot;& centerdot;& centerdot;O (30.7%) interactions, with the latter playing a key role in lattice stabilization. Crystal void mapping showed a low void volume (7.14%), suggesting efficient packing and structural stability. Raman spectroscopy, supported by calculations based on density functional theory (DFT), enabled suitable vibrational mode assignments. Thermogravimetric analysis revealed five thermal decomposition stages (300-660 K), with dehydration occurring at 304-347 K and confirming the monohydrate stoichiometry. Solubility assays in phosphate buffer (pH 6.8, 310 K) showed a 13.2% increase in the solubility of THNO3 (17.37 +/- 0.37 mg/mL) compared to the recrystallized pure TH, indicating potential for enhanced absorption and bioavailability. Antibacterial tests revealed bacteriostatic activity against Streptococcus mutans, highlighting the multifunctional activity of the new THNO3 solid dispersion. These findings underscore the relevance of formation cocrystal salts with inorganic acids as a strategy to improve physicochemical and biological properties of active pharmaceutical ingredients.

The aim of the study was to produce polymeric films as a semi-solid matrix for the loading of a binuclear Cu(II) complex made by maleate and phenanthroline ligands complexed with Cu2+ ions ([Cu2(Phen)2(Mal)2]⋅2H2O⋅CH3OH), and to characterize the structural, optical, thermal, and biological properties of the obtained crystal-loaded films. The films were prepared by adding the synthesized polycrystal at concentrations of 0.5, 1, and 2

Ethionamide (ETH) is a second-line drug widely used to treat multidrug-resistant tuberculosis (MDR-TB), but its low aqueous solubility compromises bioavailability and limits its therapeutic efficacy. To understand the ways to improve these properties, we combined experimental and computational approaches to elucidate the structural, electronic, thermal, and vibrational properties of ETH crystals. Powder X-ray diffraction analysis revealed a monoclinic crystal system (C1c1-space group), stabilized by intermolecular interactions, primarily H⋯H (49.3%) and H⋯S/S⋯H (22.1%) contacts. Energy framework analysis revealed the anisotropic nature of intermolecular interactions, with dispersion forces accounting for approximately 60% of the total stabilization energy, while Coulombic interactions showed significant directionality along the crystallographic a-axis and within the bc-plane. The total energy framework indicated that the strongest stabilization propagates along the b-axis, suggesting the formation of highly stable molecular chains, which directly influence crystal morphology and dissolution behavior. Thermal analysis confirmed ETH stability up to 162.2 °C, with melting and decomposition events characterized by endothermic peaks. Density functional theory (DFT) calculations confirmed ETH high electronic gap (7.84–8.09 eV), indicating low reactivity, while solvation studies highlighted its greater stability in polar solvents like water and methanol. Theoretical nuclear magnetic resonance studies (1H and13C) showed minimal solvent influence on chemical shifts, reinforcing the structural stability of ETH across environments. Vibrational spectroscopy, supported by DFT, identified key modes associated with the pyridine ring, NH2, and C=S groups. Hirshfeld surface analysis further revealed the dominance of hydrogen bonds and van der Waals interactions, with minimal void space (5.3%) in the crystal lattice. Electrostatic potential maps identified electron-rich regions around nitrogen atoms as potential sites for hydrogen bonding and protonation, which are relevant for pharmacological interactions. These findings offer critical insights for optimizing ETH’s solid-state properties to enhance its solubility and bioavailability, paving the way for improved formulations against MDR-TB.

The high-pressure behavior of the ammonium copper(II) Tutton salt (NH4)2Cu(SO4)2(H2O)6 (NHCuSO) is reported for the first time, investigated through in situ Raman spectroscopy in a diamond anvil cell up to 6.5 GPa, and supported by periodic density functional perturbation theory (DFPT) calculations. At ambient conditions, powder X-ray diffraction with Rietveld refinement confirmed that NHCuSO crystallized in the monoclinic system (space group P21/a, Z = 2), with its structural cohesion governed by a cooperative lattice of OH⋯O and NH⋯O hydrogen-bonds interconnecting the [Cu(H2O)6]2+, [SO4]2-, and [NH4]+ layers, as quantified by Hirshfeld surface analysis. DFPT calculations reproduced the experimental Raman frequencies and provided reliable vibrational assignments across the 70-3580 cm-1 spectral range. Under compression, the pressure-dependent Raman spectra revealed a sequence of structural instabilities, reflected by mode softening, band disappearances, and the emergence of new phonon branches at critical pressures. Two phase transitions were identified, i.e., a symmetry-lowering transformation at 2.5 GPa, driven by a reorganization of the NH⋯O hydrogen-bond topology, and a first-order transition at 4.8 GPa, yielding a distinct high-pressure polymorph with a well-defined vibrational fingerprint. A precursor regime of local structural destabilization sets in below 1.6 GPa, well before the main transitions. Additionally, the pressure-dependent DFPT optimizations further reveal that these transitions are governed by a two-stage densification mechanism: below ≈2.5 GPa the compression is accommodated by an 83% collapse of the intermolecular voids and a slight relaxation of the Cu2+ Jahn-Teller distortion, whereas above 4.8 GPa, once the voids are largely exhausted, the stress is transferred to the [Cu(H2O)6]2+ octahedron, shortening the equatorial CuO bonds and enhancing the Jahn-Teller elongation. The results of this study highlight the pivotal role of the hydrogen-bond lattice compressibility and the Jahn-Teller distortion of Cu2+ in determining the mechanical stability and pressure-phase diagram of this salt, contributing to a deeper understanding of pressure-structure-property relationships in the Tutton salt family.

This paper reports on the structural, spectroscopic, and thermal characterization of a novel polymorph (Bm form) of behenic acid (docosanoic acid, C22), crystallized from dichloromethane. The crystal structure was solved from synchrotron single-crystal X-ray diffraction (100 K), revealing a monoclinic system with space group P21/c. Hirshfeld surface analysis quantified the dominant intermolecular interactions as H & ctdot;H (90.3 %) and H & ctdot;O/O & ctdot;H (7.6 %), which stabilize a compact supramolecular lattice with a low void volume of 3.28 %. Density functional theory (DFT) calculations, including an implicit solvation model using four different solvents (i.e., dichloromethane, acetone, ethanol, and hexane), confirmed the thermodynamic stability of the polymorph and provided key chemical reactivity descriptors, indicating high electronic stability (HOMO-LUMO gap ti11 eV) and low electrophilicity. Vibrational spectroscopy (infrared and Raman) combined with DFT assignments provided a complete mode interpretation, highlighting a pronounced solvent-permittivity effect for vibrations of the carboxyl group, directly linked to its role in intermolecular interactions. Thermal analysis showed the material's stability up to 464 K and two thermal events were observed, i.e., a solid-state polymorphic transition (Bm -> C) at 343 K (Delta H ti 4.54 kJ/mol) and melting at 355 K (Delta H ti 74.68 kJ/mol). Finally, an in silico pharmacokinetic assessment underscored a significantly promising physicochemical profile, characterized by high lipophilicity, low polarity and moderate molecular weight, strengthening the C22 (Bm) polymorph potential as an advanced excipient to develop lipid matrices for controlled-release drug delivery systems.

Graphene is derived from graphite and consists of pure carbon. It can be used to produce nanostructured compounds that are incorporated in packaging materials to improve physicochemical and mechanical properties. The application of coatings made from natural polymers, such as starch, has been studied as an alternative to partially replace synthetic polymers in paper-based multilayer materials commonly used in packaging, meeting the demands of consumers with increasing environmental concerns. In this work, we describe the first-time use of a modified cassava (Manihot esculenta) starch film (4 %, m/V) coating, in which graphene has been incorporated at two different concentrations (0.2 % versus 0.4 % m/V), and characterized for its suitability for the coating of paperboard. The presence of graphene in the coating significantly influenced the physicochemical properties of the coating. The Cobb test indicated greater water retention in the coatings containing graphene, but the moisture barrier increased by 87.8 % with the one composed of 0.4 % graphene. In paperboards coated with starch containing 0.4 % graphene, the air permeance decreased by 27 % and fat barrier properties increased, compared to uncoated paperboard. The Taber stiffness was also improved with the presence of graphene in the coatings, indicating that the paperboards became more rigid. The tear strength and tensile strength of the coated paperboards also improved, while elongation and bursting remained unchanged. With the outcomes of this work, we confirm that starch coating containing graphene offers a promising alternative to polymeric lamination on cellulosic matrices, promoting sustainability in packaging and improving the final properties of the paperboard.

Artificial Intelligence (AI) plays an increasingly significant role in drug research and development, particularly in drug repurposing, which involves identifying new therapeutic indications for existing pharmacological compounds. From classical algorithms-based tools e.g. DrugRep and DrugRepo, to more recent innovations (e.g. RosettaVS, RepurposeDrugs), this paper reviews the latest AI methods (e.g. AlphaFold3, mediKanren, AdaDR, TxGNN) and their design applications in drug repurposing, particularly in machine learning, deep learning, and biological network analysis. It discusses strategies using predictive models, natural language processing, and big data analysis to accelerate the identification of promising candidates for clinical repurposing. Data availability, model interpretability, and results validation challenges are also highlighted. This review suggests that AI represents a groundbreaking tool in drug repurposing, ranging from protein structure prediction to knowledge graph reasoning, which can significantly reduce the time and costs of developing new therapies.

ABSTRACT Cardiovascular diseases (CVDs) are a cluster of ailments that impact the heart and blood vessels and are a primary public health problem of mortality on a global scale. Phytic acid, a dietary constituent frequently present in foods like seeds, has been linked to many pharmacological attributes, including anti‐cancer, antioxidant, anti‐inflammatory, anti‐calcifying, and anti‐dyslipidemia effects. The objective of this study was to review the literature reporting the effects of the dietary component phytic acid on CVDs. We conducted a comprehensive analysis of both preclinical and clinical in vivo research on the use of phytic acid for managing CVDs. We assessed the risk of bias in these studies using the Syrcle and Revman methods. In this study, two investigators were involved. One investigator was assigned the task of assessing the data, while the other investigator was responsible for analyzing any contradictions. A total of eleven studies were chosen and verified. These studies suggest that phytic acid may have potential therapeutic effects on CVDs, particularly in preclinical models of cardiovascular calcification and myocardial ischemia.

Paronychia represents an underexplored clinical condition with limited alternatives to conventional antimicrobial therapies, which are increasingly compromised by antibiotic resistance and toxicity. Here, we report for the first time the extracellular biosynthesis of silver nanoparticles (BAgNPs) using Bacillus stercoris 2AT10, a marine-derived bacterium not previously exploited for nanoparticle production. By integrating green nanotechnology with genome mining approaches, we investigated the molecular basis underlying nanoparticle formation and evaluated the potential of BAgNPs against pathogens associated with paronychia. Physicochemical characterization by ultraviolet-visible (UV-Vis) spectroscopy confirmed the presence of particles, with mean sizes ranging from 47 to 87 nm measured by dynamic light scattering (DLS). Their spherical shape was confirmed by transmission electron microscopy (TEM), whereas Fourier-transform infrared (FTIR) spectroscopy suggested the presence of hydroxyl, amide, and nitrogen-containing groups possibly associated with reducing or capping action. Genes encoding nitrate reductases, laccases, and bioactive secondary metabolites, such as bacillibactin, subtilosin A, bacillaene, bacilysin and fengycin, that may be involved in silver ion reduction and nanoparticle stabilization were identified by genome annotation using eggNOG-mapper and antiSMASH. The biosynthesized AgNPs exhibited potent broad-spectrum antimicrobial activity against paronychia-associated pathogens, notably with inhibition zones of 25.8 mm for Staphylococcus aureus and of 23.2 mm for Pseudomonas aeruginosa. The Hen's Egg Test on the Chorioallantoic Membrane (HET-CAM) assay showed the nonirritating profile of the biosynthesized particles (irritation index ≤ 1), supporting further investigation of their suitability for topical applications, pending additional biocompatibility studies. Collectively, these findings establish B. stercoris-derived BAgNPs as a promising green nanotechnology platform to address the unmet need for safe and effective prophylactic agents against bacteria associated with paronychia, with additional potential as antimicrobial preservatives for dermocosmetic formulations.

Hybrid biopolymeric sponges based on sodium alginate (SA) and bovine gelatin (BG) (1:3, w/w), incorporating copaiba oleoresin (1–3

The diaquadichlorotheophylline-copper(ii) coordination complex, [Cu(theophylline)(H2O)2Cl2], was synthesized via slow solvent evaporation and comprehensively characterized through experimental and computational approaches. X-ray powder diffraction and Rietveld refinement confirmed a triclinic crystal system (space group P1̄(C 1 i )) with pentacoordinate copper(ii) in a square-pyramidal geometry. Thermal analyses revealed thermal stability up to 358 K, with dehydration requiring 89.5 kJ mol-1 per H2O molecule. Vibrational spectroscopy (Fourier transform infrared and Raman) combined with density functional theory calculations (PBE1PBE/6-311++G(d,p)) provided suitable mode assignments and demonstrated excellent agreement between experimental and calculated spectra, including solvent effects using the IEFPCM model. Frontier molecular orbital analysis yielded the highest occupied molecular orbital-lowest unoccupied molecular orbital gaps of approximately 3.8 eV and electrophilicity indices of approximately 6.8 eV, indicating good chemical stability and biological potential. Ultraviolet-visible-near infrared spectroscopy revealed characteristic d-d transitions for pentacoordinate copper(ii) and π → π*/n → π* transitions from the theophylline ligand. Molecular docking predicted a strong in silico binding affinity to deoxyribonucleic acid (K i = 5.85 µM, binding free energy = -7.14 kcal mol-1), consistent with an intercalative mode and moderate affinity to bovine serum albumin (K i = 40.78 µM, binding free energy = -5.99 kcal mol-1). Cytotoxicity assays against PC-3 (prostate), MDA-MB-231 (breast), and HCT-116 (colorectal) cancer cell lines revealed dose-dependent activity with half-maximal inhibitory concentration values ranging from 2.91 to 3.77 µM and selectivity indices greater than 1 compared to the non-tumorigenic GM07429A cell line, with preferential activity against breast cancer. These results indicate that diaquadichlorotheophylline-copper(ii) is a promising anticancer candidate with favorable selectivity for malignant cells over healthy tissue, warranting further preclinical evaluation.

Nimesulide (NIM) is a selective COX-2 inhibitor non-steroidal anti-inflammatory drug (NSAID), generally administered orally, with a distinctive pharmacological profile, that may still lead to some gastrointestinal adverse effects. Its combination with natural polysaccharides to develop modified-release delivery systems has become a technological strategy to reduce the adverse effects. In this work, we propose the development and characterization of a hybrid composite based on sodium alginate (NaCHO), nimesulide (C13H12N2O5S), and calcium chloride (CaCl2). The synthesized hybrid composite - NaCHO-NIM-CaCl2 - was developed by adapting methods of calcium-induced ionotropic gelation, sonication, and solvent evaporation. The obtained hybrid was characterized in terms of its physicochemical properties using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Raman spectroscopy, and Fouriertransform infrared (FT-IR) spectroscopy. Theoretical studies of the vibrational properties of NIM, NIM-CaCl2 and the hybrid NaCHO-NIM-CaCl2 were performed using density functional theory (DFT) for the first time. Electronic properties of the NIM crystal were elucidated, revealing that it is a semiconductor compound. For proof of concept, cell viability assay and in vitro release tests were performed to evaluate the potential biological application of NaCHO-NIM-CaCl2.

Tuberculosis (TB) treatment, particularly against drug-resistant strains, is significantly hindered by the poor aqueous solubility and pronounced adverse effects of second-line drugs such as ethionamide (ETH). This study presents the successful development of a novel pharmaceutical cocrystal of ETH with sorbic acid (SA), which is designed to overcome these critical limitations. The ETH-SA cocrystal, synthesized via slow solvent evaporation and characterized by single-crystal X-ray diffraction, crystallizes in the monoclinic system within the P21/n-space group. Structural analysis reveals a primary O-H & centerdot;& centerdot;& centerdot;N hydrogen bond (distance = 1.848 & Aring;, angle = 174.20 degrees) between the carboxylic acid group of SA and the pyridinic nitrogen of ETH, forming a stable 1:1 supramolecular heterosynthon, further stabilized by C-H & centerdot;& centerdot;& centerdot;O contacts and pi-pi stacking interactions. Hirshfeld surface and void analyses quantified the intermolecular contacts, revealing efficient molecular packing with a low void volume (10.6%). Thermal analyses demonstrated thermal stability up to 384 K, with a melting point at 393 K, significantly higher than that of previously reported ETH solid dispersions, attributed to the hydrogen bonding lattice in the supramolecular structure. Periodic density functional theory (DFT) calculations provided insights into the electronic structure, revealing an energy band gap of 2.06 eV. The experimental Raman spectrum showed excellent agreement with the theoretical predictions. Dissolution studies demonstrated a substantial 2.75-fold enhancement in the aqueous solubility of the ETH-SA cocrystal compared to pure ETH, representing a significant improvement over earlier related ETH formulations. In silico absorption, distribution, metabolism, and excretion data confirmed that the cocrystal retains favorable pharmacokinetic and drug-likeness profiles while maintaining the therapeutic activity of ETH. These results establish the ETH-SA cocrystal as a promising pharmaceutical strategy with optimized physicochemical properties for enhanced therapeutic efficacy and improved patient compliance in TB treatment.

The synthesis, structural characterization, spectroscopic features, solubility, and anti-inflammatory properties of a novel manganese(II)-creatine coordination polymer, {[Mn(μ2-CRN)2(H2O)2](NO3)2·2H2O}n (CRN = creatine), are reported. Single-crystal X-ray diffraction revealed a one-dimensional coordination polymer crystallizing in the triclinic system (P1¯), in which the Mn2+ center resides on a crystallographic inversion center and adopts a regular octahedral geometry defined by four carboxylate oxygen atoms from four syn-syn μ2-bridging CRN ligands and two trans-aqua ligands; adjacent Mn2+ centers are doubly bridged along the crystallographic a axis (Mn⋯Mn = 4.7085 Å). Hirshfeld surface analysis demonstrated that the framework is dominated by O⋯H/H⋯O and N⋯H/H⋯N contacts, yielding compact packing with only 6.37% void volume. Periodic density functional theory calculations supported the assignment of Raman and infrared vibrational modes. Thermal analyses revealed a three-stage decomposition (25-400 °C) involving sequential loss of lattice water, coordinated water, nitrate, and organic ligand. In vitro anti-inflammatory evaluation against lipopolysaccharide-stimulated RAW 264.7 macrophages showed no cytotoxicity up to 50 μM and an inverse concentration-dependent inhibition of nitric oxide production (maximal reduction of 25 ± 2% at 0.78 μM). Cell-free control experiments confirmed that nitrate counterions do not contribute to nitrite generation or interfere with the Griess reaction, validating the biological origin of the observed inhibition. Aqueous solubility was determined experimentally as 1.00 mM (0.514 g/L) at 25 °C, and in silico pharmacokinetic parameters indicate low gastrointestinal absorption, absence of P-glycoprotein substrate behavior, and no cytochrome inhibition, positioning this bioinspired compound for further mechanistic investigation of inflammatory pathways.

Aquaculture production is often linked to improper use of chemotherapeutic agents for pathogen control, leading to adverse effects in organisms and environment. As an alternative over these toxicological agents, in this study we propose the development of zinc oxide (ZnO) nanoparticles using ethanolic extract of red Aroeira (Schinus terebinthifolia) (EERA) and tested them against fish pathogens. Green synthesized ZnO nanoparticles had a mean hydrodynamic diameter of ca. 150 nm, and showed a broad-spectrum antibacterial activity, as well as antifungal and antiparasitic activities against Saprolegnia parasitica and Ichthyophthirius multifiliis, at the highest tested concentrations (10 and 15 mg/mL). The extract alone showed antibacterial activity against Aeromonas hydrophila, but not against Streptococcus agalactiae, suggesting a synergistic effect between EERA and ZnO nanoparticles. These findings demonstrate that green ZnO nanoparticles hold significant potential as a multifunctional antimicrobial agent for managing various pathogens in aquaculture, offering an environmentally friendly alternative to conventional chemotherapeutics.

We report the synthesis and comprehensive characterization of a ternary copper-(II) complex, [Cu-(l-isoleucine)-(1,10-phenanthroline)-(H2O)]-Cl·2H2O, combining single-crystal X-ray diffraction (SCXRD), ultraviolet-visible (UV-vis), Fourier-transform infrared (FT-IR), and Raman spectroscopy, and Hirshfeld surface analyses, with molecular docking, and in vitro cytotoxicity assays. SCXRD reveals a distorted square-pyramidal Cu-(II) center (monoclinic, P21 (C 2 2) space group, 300 K). Hirshfeld analysis indicates that H···H (52.8%), O···H/H···O (17.4%), and Cl···H/H···Cl (10.3%) contacts dominate the crystal packing. Docking of the biologically main cation [Cu-(l-Ile)-(phen)-(H2O)]+ predicts favorable binding to deoxyribonucleic acid (ΔG = -8.26 kcal/mol) and bovine serum albumin (ΔG = -7.17 kcal/mol), supported by π-π and electrostatic interactions. The complex exhibits a dose-dependent antiproliferative effect against SiHa cervical carcinoma cells (IC50 = 2.57 μM) and comparable toxicity toward GM07492A fibroblasts (IC50 = 2.77 μM), yielding a selectivity index of 1.08. These findings establish a structurally validated Cu-(II) mixed-ligand complex and provide an integrated experimental-computational framework for future optimization toward improved biological selectivity.