Sulfaguanidine-based schiff bases, synthesis, crystal structure, FT-IR, hirshfeld surface analysis, and concise computational study

The current work reports the synthesis of three new sulfaguanidine-based Schiff bases: (E)-N-(diaminomethylene)-4-((2-hydroxy-3-methoxybenzylidene)amino)benzenesulfonamide (DHMB), (E)-N-(diaminomethylene)-4-((2,4-dichlorobenzylidene)amino)benzenesulfonamide (DCLB), and (E)-N-(diaminomethylene)-4-((4-fluoro-2-hydroxybenzylidene)amino)benzenesulfonamide (DFHB). The synthesized derivatives were initially characterized by FT-IR spectroscopy to confirm the presence of the azomethine linkage (HC = N), a characteristic aspect of Schiff bases. Then, single-crystal XRD analysis was performed for structural elucidation. The structures of DHMB and DFHB adopt the enol tautomeric form, stabilized by intramolecular O-H & ctdot;N hydrogen bonding, whereas DCLB did not exhibit tautomerism. DFHB exists in a solvated form, while the other structures are non-solvated. Hirshfeld surface analysis reveals several intermolecular interactions, which contribute to the stabilization of the compounds in the solid state. Furthermore, molecular docking simulations and DFT calculations were employed to explore the structural, biological, and electronic characteristics of the synthesized derivatives. The HOMO-LUMO energy gap analysis indicated that DHMB has the highest reactivity, with a gap of 3.97 eV. Molecular docking against the HER2 kinase domain demonstrated that DHMB possesses the strongest binding affinity (-8.92 kcal/mol). Overall, DHMB displayed enhanced electronic properties and biological potential, suggesting its promise as a lead compound for HER2-targeted anticancer drug development.