Synthesis, X-ray crystallography, DFT study of 5-chloro-2-((2-methyl-6-(trifluoromethyl)pyrimidin-4-yl)oxy)aniline, and its antifungal activity

Spectroscopic characterization and DFT-based structural analysis of a novel sulfonyl-acetamide imidazole derivative with multi-target protein docking studies

This study describes the synthesis and thorough identification of N-[4-[4-[2-(2-hydroxyphenyl)-4,5-diphenyl-1H-imidazole-1-yl]phenyl]sulfonylphenyl]acetamide (NHDIPSA) using DFT-based computerized methods and experimental spectroscopy (liquid chromatography mass spectrometry, FT-Raman/IR, 13C NMR, and 1H NMR analysis). To evaluate its chemical reactivity, FMO and MEP surface analyses were performed, while topological studies (ELF, LOL, and NCI) elucidated the compound's intermolecular interactions. Computational PES analysis is carried out to understand the relationship between molecule energies and their geometrical structures. Vibrational and NMR assignments obtained at the B3LYP/6-311G(d,p) level showed close agreement with experimental FT-IR, FT-Raman, and NMR data, with RMSD values of 0.45–3.16 ppm for NMR chemical shifts. Docking simulations returned binding energies between −5.49 and −10.45 kcal mol−1 across the five target proteins, indicating favourable structural complementarity. Together, these results establish a validated structural and electronic profile for NHDIPSA and identify candidate protein targets for future experimental follow-up. No enzyme inhibition, antimicrobial, or cell-based assays were performed in this study; the biological terms used here refer to computationally predicted target compatibility, and experimental validation is left for future work.

Crystal structure, intermolecular interactions, Hirshfeld surface analysis, theoretical studies and biological evaluation of (E)-5-(benzyloxy)-2-{[(2,5-dimethoxyphenyl)imino]methyl}phenol, a new Schiff base.

In the present work, we report on the synthesis, characterization and biological evaluation of (E)-5-(benzyloxy)-2-{[(2,5-dimethoxyphenyl)imino]methyl}phenol Schiff base, C22H21NO4 (BDIMPh). The compound was synthesized via the condensation reaction between 4-benzyloxy-2-hydroxybenzaldehyde and 2,4-dimethoxyaniline. It was characterized using 1H, 13C NMR and FT-IR spectroscopies, and its crystal structure was determined by single-crystal X-ray crystallography. BDIMPh crystallizes with two crystallographically independent molecules in the asymmetric unit. The structural model also includes the reported disorder features, which are discussed on the basis of the crystallographic refinement. The two molecules of BDMPh have the same E configuration about the C=N bond. In the crystal, the independent molecules are linked to their inversion-related molecule via C-H...O hydrogen bonds. Hirshfeld surface analysis and two-dimensional fingerprint plots were used to quantify the intermolecular contacts present in the crystal. Quantum theory of atoms in molecules (QTAIM) analysis was performed to characterize selected intra- and intermolecular interactions. The optimized geometry showed good agreement with the experimental X-ray crystal structure. The antioxidant activity of BDIMPh was evaluated using the DPPH and ABTS radical-scavenging assays. BDIMPh exhibited moderate radical-scavenging activity under the experimental conditions and showed higher IC50 values than the reference antioxidants. The enzyme inhibitory activity of BDIMPh was investigated against acetylcholinesterase (AChE), glutathione S-transferase (GST), α-glucosidase and tyrosinase. BDIMPh exhibited measurable enzyme-dependent inhibitory activity against AChE, GST and α-glucosidase, whereas comparatively weak inhibition was observed against tyrosinase. The IC50 values were 2.899 ± 0.851 µM for AChE, 3.850 ± 0.721 µM for GST and 3.284 ± 0.738 µM for α-glucosidase. Compared with the corresponding reference inhibitors, BDIMPh showed a slightly higher IC50 value than donepezil for AChE, a slightly lower IC50 value than ethacrynic acid for GST and a higher IC50 value than acarbose for α-glucosidase. These results indicate an enzyme-dependent inhibitory profile rather than uniformly superior activity relative to the reference inhibitors.

Synthesis, characterization and molecular docking studies of novel 6-Imino-2-Methyl-4-substituted- 6H -1,3-Thiazine-5-Carbonitrile derivatives as potential antibacterial agents

Novel 6-imino-2-methyl-4-substituted-6H-1,3-thiazine-5-carbonitrile derivatives were synthesized via cyclocondensation of thioacetamide and bis(methylthio)methylene malononitrile in DMF using K 2 CO₃. The key 4-methylthio intermediate underwent nucleophilic substitution with various anilines, phenols, heterocyclic amines, and active methylene compounds to produce a diverse library. All structures were confirmed using IR, 1H NMR, 13C NMR and mass spectrometry. The antibacterial potential of twelve selected derivatives was evaluated through molecular docking against the DNA Gyrase B ATP-binding pocket (PDB: 1KZN). Utilizing CB-Dock2, AutoDock Vina, and PLIP analysis, the study predicted binding affinities and interaction profiles. Favourable binding energies and significant intermolecular interactions highlight these thiazine derivatives as promising leads for further antibacterial development.

A Synergistic Approach to the Structural Characterization of 2-(Morpholin-4-yl)quinoline-3-carbaldehyde by Solution and Solid-State NMR Spectroscopy, Supported by Single-Crystal X-Ray Diffraction and DFT Calculations.

Heterocyclic building blocks incorporating quinoline and morpholine units are central to the synthesis of a wide range of biologically active molecules, where conformational preferences and solid-state organization can directly influence the reactivity and functional performance. In this study, the molecular structure of 2-(morpholin-4-yl)quinoline-3-carbaldehyde (abbreviated as MQ3CA), a key intermediate for quinoline-, morpholine-, and piperazine-based drug scaffolds, is examined using a synergistic combination of solution and solid-state NMR spectroscopy, complemented by single-crystal X-ray diffraction (SC-XRD) and density functional theory (DFT) calculations. Complete resonance assignments, including chemical shifts, scalar coupling constants, and through-bond and through-space correlations, were achieved using 2D J-resolved, COSY, NOESY, HSQC, and HMBC experiments, enabling an unambiguous description of molecular connectivity and conformation in solution. Solid-state 13C CPMAS-TOSS and two-dimensional 1H-13C HETCOR NMR measurements provided atomic-level insight into the solid-state organization of MQ3CA. The observed differences between the solid- and solution-state 13C chemical shifts indicate the influence of crystal packing and weak intermolecular interactions, consistent with the crystallographic analysis. PXRD analysis further confirmed the absence of polymorphic phases in the investigated sample. The SC-XRD information supports that the morpholine ring adopts a chair conformation with the quinoline ring positioned in the equatorial plane, whereas C-H···O hydrogen bonds and π···π interactions dominate the crystal packing. DFT-derived electronic descriptors further support the experimentally observed structural stability. This work demonstrates the effectiveness of integrated magnetic resonance approaches for resolving structure-packing relationships in pharmaceutically relevant intermediates.

Synthesis, crystal structure, Hirshfeld surface analysis and halogen-involving interactions in a bromo/chloro-substituted Schiff base 1-(3-bromo-4,5-dimethoxyphenyl)-N-(2,4-dichlorophenyl)methanimine.

Synthesis, Crystal Structure, DFT, MEP, FMOs, Hirshfeld Analysis and Antitumor Activity Assay of 4-[(4-Fluorophenyl)amino]-6-pentylpyrido[4,3-d]pyrimidin-5(6H)-one