A series of sulfadiazine based compounds: synthesis, characterizations, antibacterial study, DFT and theoretical molecular docking analysis
Journal of Molecular Structure, cilt.1367, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 1367
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.molstruc.2026.146185
- Dergi Adı: Journal of Molecular Structure
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, INSPEC
- Anahtar Kelimeler: Antibacterial activity, Crystal structure, DFT, Hirshfeld surface analysis, Molecular docking, Sulfadiazine
- Süleyman Demirel Üniversitesi Adresli: Evet
Özet
Sulfadiazine-based compounds were synthesized by refluxing sulfadiazine with 2,4-Dichlorobenzaldehyde and 2-fluoro-6-hydroxybenzaldehyde resulting 4-(((2,4-dichlorophenyl)(methoxy)methyl)amino)-N-(pyrimidin-2-yl)benzenesulfonamide (DAPB), 4-(((2,4-dichlorophenyl)(methoxy)methyl)amino)-N-(pyrimidin-2-yl)benzenesulfonamide (P-DAPB), and (E)-4-((2-fluoro-6-hydroxybenzylidene)amino)-N-(pyrimidin-2-yl)benzenesulfonamide (FPAB). Compounds are characterized by FT-IR and single crystal XRD. Structure of (FPAB) adopted enol tautomeric Schiff base form supported by OH⋯[jls-end-space/]N bonding, while (DAPB) and (P-DAPB) have no tautomerism. The compound FPAB demonstrated efficient antibacterial activity with minimium inhibitory concentration (MIC) values (1.56 to 28 µg/mL) and zones of inhibitions (17 to 26 mm) against the tested bacterial strains. Solid state assembly of compounds stabilized by various intermolecular interactions, which were explored through Hirshfeld surface analysis. Geometry optimizations were performed at the B3LYP-D3(BJ)/6–311 g (2d,2p) level, revealing stable conformations in excellent agreement with experimental X-ray data. Molecular electrostatic potential (MEP) mapping identified the sulfonyl oxygen atoms as electrophilic centers and the amine hydrogens as preferred nucleophilic sites. Frontier molecular orbital (FMO) analysis indicated that FPAB possesses the smallest HOMO-LUMO energy gap (4.11 eV), suggesting higher charge-transfer efficiency and greater chemical reactivity than its analogues. Molecular docking simulations with the E-coli protein (PDB ID: 2VF5) demonstrated strong binding affinities, particularly for FPAB (ΔG = -7.19 kcal/mol), which forms multiple contacts with the active-site residues. The combined theoretical and docking results highlight FPAB as a promising lead compound with potential antibacterial activity and emphasize the strong correlation between its electronic structure and biological performance.