Two new 2(E)-pyranylidene-1,5-benzodiazepine derivatives, namely: 3,4-Dihydro-2-(2,4-dioxo-6-methylpyran-3-ylidene)-4-(3-pyridine-phenyl)-1,5-benzodiazepine 3 and 2(E)-3,4-Dihydro-2-(2,4-dioxo-6-methylpyran-3-ylidene)-4-(3,4,5-méthoxy-phenyl)-5-N-acetyl-1,5-benzodiazepine 6 was synthesized and characterized by NMR spectroscopy and were also analyzed by single-crystal X-ray diffraction. Their molecular packing and supramolecular features were investigated through Hirshfeld surface analysis and interaction energy calculations, which revealed dominant H···H contacts along with secondary C–H···O and π···π interactions. Molecular docking studies performed with the human α1β3γ2 GABAA receptor (PDB: 6HUO) showed favorable binding affinities, suggesting efficient interaction with the benzodiazepine binding site. Furthermore, drug-likeness and ADMET properties assessments indicate that both compounds comply with Lipinski and Veber rules, exhibit good predicted oral absorption, and are in the drug-like space. Compound 3 emerges as a promising candidate, with improved permeability and a more favorable toxicity profile. In contrast, compound 6 exhibits greater intrinsic solubility and prolonged systemic exposure, albeit with a potential hepatotoxicity signal. These results highlight the potential of 2(E)-pyranylidene-1,5-benzodiazepine skeletons as promising candidates for further biological evaluation and the design of novel GABAA receptor modulators.

In the title mol-ecule, C25H21N5O2, the benzyl-triazole moiety and the phenyl portion of the 3-(2-oxo-2-phenyl-eth-yl) group are disordered over two sets of sites. In the crystal, layers of mol-ecules parallel to the ab plane are generated by C-H⋯O and C-H⋯N hydrogen bonds, enclosing R 2 2(10) and R 2 2(16) ring motifs, and C-H⋯π(ring) inter-actions. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (41.3%), H⋯C/C⋯H (31.1%), H⋯O/O⋯H (13.2%) and H⋯N/N⋯H (10.7%) inter-actions.

In the title molecule, C 25 H 21 N 5 O 2 , the benzyltriazole moiety and the phenyl portion of the 3-(2-oxo-2-phenylethyl) group are disordered over two sets of sites. In the crystal, layers of molecules parallel to the ab plane are generated by C—H...O and C—H...N hydrogen bonds, enclosing R 2 2 (10) and R 2 2 (16) ring motifs, and C—H...π(ring) interactions. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H...H (41.3%), H...C/C...H (31.1%), H...O/O...H (13.2%) and H...N/N...H (10.7%) interactions.

The title molecule, C22H20ClN3O3S, adopts a shallow cup-shaped conformation with the chlorobenzamide portion as the bottom. A puckering analysis of the five-membered ring indicates an envelope conformation. In the crystal, helical chains along the a-axis direction are formed by N—H...O hydrogen bonds reinforced by C—H...π(ring) and weak π-stacking interactions. No directed interactions between chains appear to exist. A Hirshfeld surface analysis was performed.

The title molecule, C 9 H 10 N 2 , exhibits whole-molecule disorder in a 0.849 (4)/0.151 (4) ratio. The bicyclic portion is planar. In the crystal, a layer structure parallel to the ac plane is generated by N—H...N hydrogen bonds and C—H...π(ring) interactions. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H...H, C...H/H...C and N...H/H...N interactions.

As part of a drug-design effort toward new antibacterial agents, two 2-substituted 1,2,4-triazolo[3,2-b] [1,3]thiazine derivatives (NO3, NO4) were synthesized via alkylation of 3-alkyl-1,2,4-triazole-5-thiones (NO1, NO2) under phase-transfer catalysis in a heterogeneous medium. Structures were established by 1H/13C NMR, IR, and HRMS; single-crystal X-ray diffraction of NO3 confirmed selective cyclization at the triazole N1 position. Density functional theory (DFT) calculations were performed on compound NO3 to elucidate its key noncovalent interactions and electronic structural features using molecular electrostatic potential (MEP), quantum theory of atoms in molecules (QTAIM), independent gradient model (IGM), and natural bond orbital (NBO) analyses. In vitro antibacterial testing showed activity for NO2 and NO4 against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). Agar-diffusion halos reached 14.20 mm, and minimum inhibitory concentrations (MICs) were 0.25 mg/mL for NO4 and 0.5 mg/mL for NO2. Minimum bactericidal concentrations (MBCs) of 2 mg/mL indicated a bactericidal effect against S. aureus ATCC 29,213 and a bacteriostatic effect against MRSA. Molecular docking supported strong binding of NO4 to penicillin-binding protein 2a (PBP2a), and in-silico ADMET predictions suggested acceptable oral bioavailability. Overall, NO4 emerges as a promising anti-staphylococcal candidate, with NO2 and NO4 as scaffolds for further optimization.

Meet IFSEG, a fresh and exciting derivative of pyranylidene-1,5-benzodiazepine, officially named (E) 2-(2,4-dioxo-6-methylpyran-3-ylidene)-4-(4-hydroxy-3-methoxyphenyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine. This compound was carefully crafted and then explored in depth using nuclear magnetic resonance (NMR) spectroscopy alongside single-crystal X-ray diffraction. It settles into a neat monoclinic crystal structure within the P2₁/n space group. Given the impressive biological versatility of pyranylidene-1,5-benzodiazepines, we took a closer look at how IFSEG performs as a corrosion inhibitor for mild steel in a 1 M HCl environment. Using electrochemical impedance spectroscopy and potentiodynamic polarization techniques, we found that it exhibits impressive inhibition efficiencies, peaking at 91.6% and 93.6%, respectively. To really understand how it works at the molecular level, we combined quantum-chemical calculations with Monte Carlo and molecular dynamics simulations. Diving into its electronic structure—looking at HOMO–LUMO, electron density, and molecular electrostatic potential—revealed well-defined donor sites (N, O atoms) that make for a strong, stable bond with the Fe (110) surface. Our simulations also confirmed that these interactions hold steady and maintain their strength even under thermal stress. The close match between our theoretical predictions and experimental findings positions IFSEG as a standout candidate for creating efficient, long-lasting anticorrosion solutions.

There is high demand for high-performance, effective corrosion inhibitors for industrial applications in aggressive, acidic media. In this study, a novel pyrazole-based compound, (E)-N-(2-(1-(2-hydroxy-6-methyl-4oxo-4H-pyran-3-yl)ethylideneamino)phenyl)-2-(5-methyl-1H-pyrazol-3-yl)acetamide (HMP), was synthesized and evaluated as a corrosion inhibitor for C38 steel in 1 M HCl solution. The anticorrosive performance was investigated using weight-loss measurements, electrochemical impedance spectroscopy (EIS), and potentiodynamic polarization (PDP). Surface morphology of the uninhibited and inhibited C38 steel was studied using Scanning Electron Microscopy (SEM). Potentiodynamic polarization measurements confirmed that HMP acts as a mixed-type inhibitor, suppressing both anodic and cathodic reactions. The inhibition efficiency reached 94.3% at 1 mM, significantly outperforming the blank solution and demonstrating high stability. The data extracted from EIS were fitted to an equivalent circuit, revealing a marked increase in polarization resistance and a decrease in double-layer capacitance, confirming the formation of a protective adsorbed layer. Thermodynamic studies indicated that the adsorption process follows the Langmuir isotherm model. Furthermore, molecular-level insights into the adsorption interactions between HMP and the Fe(110) surface were provided via Density Functional Theory (DFT) calculations and Monte Carlo (MC) simulations. These combined experimental and theoretical findings highlight HMP as a highly effective and eco-friendly corrosion inhibitor suitable for industrial applications.

The design of organic molecular crystals with tailored properties requires a detailed understanding of the non-covalent interactions governing their assembly. In this context, a novel triazole–quinoxaline derivative, 1-((1-(2-hydroxyethyl)-1H-1,2,3-triazol-4-yl)methyl)-3-phenylquinoxalin-2(1H)-one, was synthesized and characterized both structurally and computationally in the solid state. The asymmetric unit contains two independent molecules (A and B, Z’ = 2) and two water molecules, which form a three-dimensional supramolecular network through O–H⋯O, C–H⋯N, π–π, and C–H⋯π interactions. Crystallographic analysis reveals subtle conformational differences between A and B that are correlated with variations in π–π stacking geometries and hydrogen-bonding patterns, reflecting the interplay between conformational flexibility and supramolecular assembly. Hirshfeld surface analysis quantifies contact contributions, while MEP mapping rationalizes noncovalent interaction preferences, and energy framework calculations provide the energetic basis of the crystal structure, including the role of solvent water molecules. Cooperative effects within the water-mediated O–H⋯O network were investigated using two trimers (A⋯water⋯B) employing density functional theory (B3LYP-D3(BJ)/def2-TZVPP), and both trimers exhibit positive cooperativity. Furthermore, QTAIM and NBO analyses reveal systematic increases in electron density at bond critical points and enhancements in donor–acceptor stabilization energies when both hydrogen bonds are present.

Systematic biological re-evaluation of synthetically accessible scaffolds can reveal substitution-dependent activity and provide experimentally grounded directions for lead optimization. In this study, the 3-phenyl-1,2,4-triazole-5-thione (TTH) and its para-bromophenyl analogue (TTB) were prepared by established routes, characterized by FT-IR, 1H/13C NMR, and HRMS, and evaluated as a matched molecular pair. Antibacterial, α-amylase inhibitory, and antioxidant activities were measured in vitro, alongside an OECD TG 423 acute oral limit test. DFT calculations, molecular docking, 100-ns molecular dynamics simulations, and in silico ADME predictions were used to interpret the effect of para-bromination. TTH showed the strongest antibacterial activity, particularly against S. aureus (MIC 0.625 μg/mL; MBC 5 μg/mL), whereas TTB inhibited α-amylase more strongly than TTH (IC50 1154.28 ± 8.55 versus 2416.55 ± 7.95 μg/mL), although both were less active than acarbose. TTH also showed the greater antioxidant response (DPPH IC50 21.87 ± 2.59 μg/mL). No mortality or severe clinical signs were observed after a single 2000 mg/kg dose during the 14-day observation period. The calculations supported distinct interaction profiles: TTH formed more persistent complexes with the selected antibacterial targets, whereas the para-bromo substituent altered electronic and lipophilic properties and the α-amylase interaction pattern. Thus, the contribution of this work is an integrated experimental-computational comparison showing that a single para substituent redirects antibacterial, enzyme-inhibitory, and redox behavior. These results define a focused structure-activity hypothesis for broader analogue synthesis, mechanistic validation, pharmacokinetic testing, and in vivo efficacy studies.

The thiazine ring in the title molecule, C23H19NOS, exhibits a screw-boat conformation and is significantly folded along the S...N axis. In the extended structure, aided by C—H...π(ring) interactions, the molecules pack in wave-like layers parallel to the bc plane. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H...H (50.3%) and H...C/C...H (35.9%) interactions. An evaluation of the electrostatic, dispersion and total energy frameworks in the crystal structure indicates that dispersion energy contribution dominates.

Ten acyclonucleoside analogs of 1,4-benzothiazine and their sulfone derivatives (3a,b-8a,b) were synthesized using alkylation reactions under phase-transfer catalysis (PTC) conditions. The reactions were conducted under optimized conditions, with reaction times ranging from 1.5 to 2 h and yields varying between 70% and 76%. All the synthesized products were characterized using 1H and 13C-NMR spectroscopy. Additionally, the structures of compounds 4a, 6b, 7a, and 8b were confirmed through single-crystal X-ray diffraction analysis. Spectral data were also calculated using density functional theory (DFT) at the B3LYP/6-311++G(d,p) level and compared with experimental results to better understand the non-binding intermolecular interactions in the solid-state crystal packing. Two-dimensional (2D) and three-dimensional (3D) Hirshfeld surface analyses were performed to identify the closest atomic contacts in the studied molecules. The structures of compounds 4a, 6b, 7a, and 8b were optimized and evaluated for their HOMO and LUMO energies, along with their corresponding orbital representations. A strong correlation was observed between the experimental and calculated results. Finally, molecular docking studies of compounds 4a, 6b, 7a, and 8b were performed to investigate their binding patterns with inhibitory targets from the Protein Data Bank (PDB: 4P8K-A chain: DprE1: decaprenylphosphoryl-beta-D-ribose-2 '-epimerase) from Mycobacterium tuberculosis, using the AutoDock Vina program.

A new series of acylated and alkylated derivatives of pyran-3-ylidene-1,5-benzodiazepine has been prepared, and their structures were confirmed using NMR spectroscopy. Additionally, five pyran-3-ylidene-1,5-benzodiazepine compounds were analyzed through single-crystal X-ray diffraction. Hirshfeld surface analysis was performed using several key parameters, including normalized contact distance (dnorm), external (de) and internal (di) distances, curvature, and fragment patches, which enabled detailed visualization of electron density and intermolecular interactions. Molecular docking studies were conducted to assess the binding affinities of these benzodiazepine derivatives to the gamma-aminobutyric acid (GABA) receptor [Protein Data Bank (PDB) identification code: 6HUP], using valium as a reference ligand. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling demonstrated that most compounds complied with Lipinski’s rules, exhibited good permeability through human colon carcinoma (Caco-2) cells, and showed low hepatotoxic and carcinogenic potential. The high passive permeability through Madin–Darby canine kidney (MDCK) cells and the absence of mutagenicity further support the potential of these compounds for development. Overall, the derivatives displayed improved profiles for advancement as clinical candidates based on in silico predictions, indicating that further experimental validation is required.

Two new 2-aryl-methyl-idene derivatives of benzo-1,4-thia-zin-3-one, namely, (Z)-2-(4-methyl-benzyl-idene)-2H-benzo[b][1,4]thia-zin-3(4H)-one, C16H13NOS, 1, and (Z)-2-(furan-2-yl-methyl-idene)-2H-benzo[b][1,4]thia-zin-3(4H)-one, C13H9NO2S, 2, are rare examples of a nearly planar structure of the 1,4-thia-zin-3-one core stabilized by conjugation. Their supra-molecular structures are very similar, being dominated by assembly of inversion dimers through highly directional reciprocal N-H⋯O bonds [N⋯O = 2.822 (2) Å for 1; 2.881 (3) Å for 2]. Weaker forces are represented by C-H⋯O, C-H⋯π and stacking inter-actions, with more inter-actions in the case of furfuryl-idene 2, and they are important for consolidation of the structures. This is consistent with the results of Hirshfeld surface analysis and calculated inter-action energies. Doubling the number of O atoms, when moving from 1 to 2, results in even larger increase in fractions of O⋯H/H⋯O contacts [7.6 to 18.6%] due to extensive inter-actions with the furyl-O acceptor and this contributes to higher packing index in the case of 2. The far superior energetics in the structures are related with the formation of hydrogen-bonded dimers [-73.3 and -72.9 kJ mol-1, for 1 and 2, respectively], followed by dispersion forces and weak C-H⋯O bonding. Identification of reliable 1,4-thia-zin-3-one based supra-molecular synthons is important for selective targeting for biomedical applications.

A new 1,2,4-triazine derivative, 5,6-diphenyl-3-(prop-2-yn-1-ylthio)-1,2,4-triazine (4) has been synthesized through the condensation of 5,6-diphenyl-1,2,4-triazine-3-thiol with propargyl bromide in acetone solution in the presence of triethylamine at room temperature for one hour. Its chemical structure was elucidated from spectral data (1H NMR, 13C NMR, FT-IR, FT-Raman, UV/Vis, and mass spectrometry) and confirmed by a single crystal X-ray diffraction analysis. Geometrical optimization of the molecular structure was performed at the B3LYP/6-311++G(d,p) level of theory. The intercontacts between different units in the crystal of 4 were explored by a Hirshfeld surface analysis (HSA), which reveals that H...H contact has the highest contribution of intermolecular contacts. The anticancer activity of 4 was explored by estimating its binding affinity into the binding site of human DNA topoisomerase as the molecular target of various anticancer compounds using molecular docking. This study indicated 4 to fit well into the DNA topoisomerase binding site and to form a stable complex with its amino acids. The ADMET properties reveal that 4 obeys Lipinski's rule of five, has high gastrointestinal (GI) absorption, and may exhibit penetration through the Blood-Brain Barrier (BBB).

The heterocyclic compound N-{2-[2-(5-methyl-1H-pyrazol-3-yl)acetamido]-phenyl}benzamide monohydrate (MPAPB) was synthesized and structurally characterized by using nuclear magnetic resonance (NMR), mass spectrometry, and infrared (IR) spectroscopy. Its corrosion inhibition performance for C38 in 1 M HCl was evaluated by using gravimetric weight loss measurements, electrochemical impedance spectroscopy (EIS), and potentiodynamic polarization (PDP) techniques. MPAPB demonstrated a high inhibition efficiency of 90.2% at a concentration of 1 mM, accompanied by a substantial decrease in the corrosion current density. Electrochemical results revealed that MPAPB acts as a mixed-type inhibitor, reducing both anodic and cathodic reactions, while increasing the charge transfer resistance (R p) and decreasing the double-layer capacitance (C dl), indicative of effective surface adsorption. The adsorption behavior of MPAPB was consistent with that of the Langmuir adsorption isotherm, suggesting a combination of physical and chemical adsorption mechanisms. Density functional theory (DFT) calculations and molecular dynamics (MD) simulations further elucidated the interaction between the MPAPB and the steel surface, highlighting the role of electron-donating heteroatoms and π-electron systems in adsorption. These theoretical findings were in agreement with the experimental results, confirming the formation of a protective layer that inhibits corrosion.

In the title compound, the terminal benzimidazole moieties are inclined to one another by about 68°. In the crystal, tetra­molecular strands are generated by C—H⋯N hydrogen bonds and C—H⋯π(ring) inter­actions and are linked by C—H⋯π(ring) and π-stacking inter­actions.

The title compound, C21H18N2O4, contains non-planar diazepine (in a boat–sofa conformation) and pyran (envelope) rings. In the crystal, O—H...O and N—H...O hydrogen bonds link the molecules, enclosing R22(16) and R22(24) ring motifs, to generate [110] chains. Very weak π–π stacking interactions between the phenyl rings of adjacent molecules with an inter-centroid distance of 4.0264 (9) Å help to consolidate a three-dimensional architecture. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H...H (45.1%), H...O/O...H (23.2%) and H...C/C...H (19.2%) interactions.

Two new 2-arylmethylidene derivatives of benzo-1,4-thiazin-3-one, namely, (Z)-2-(4-methylbenzylidene)-2H-benzo[b][1,4]thiazin-3(4H)-one, C16H13NOS, 1, and (Z)-2-(furan-2-ylmethylidene)-2H-benzo[b][1,4]thiazin-3(4H)-one, C13H9NO2S, 2, are rare examples of a nearly planar structure of the 1,4-thiazin-3-one core stabilized by conjugation. Their supramolecular structures are very similar, being dominated by assembly of inversion dimers through highly directional reciprocal N—H...O bonds [N...O = 2.822 (2) Å for 1; 2.881 (3) Å for 2]. Weaker forces are represented by C—H...O, C—H...π and stacking interactions, with more interactions in the case of furfurylidene 2, and they are important for consolidation of the structures. This is consistent with the results of Hirshfeld surface analysis and calculated interaction energies. Doubling the number of O atoms, when moving from 1 to 2, results in even larger increase in fractions of O...H/H...O contacts [7.6 to 18.6%] due to extensive interactions with the furyl-O acceptor and this contributes to higher packing index in the case of 2. The far superior energetics in the structures are related with the formation of hydrogen-bonded dimers [−73.3 and −72.9 kJ mol−1, for 1 and 2, respectively], followed by dispersion forces and weak C—H...O bonding. Identification of reliable 1,4-thiazin-3-one based supramolecular synthons is important for selective targeting for biomedical applications.