Synthesis, spectroscopic characterization, DFT study, and antibacterial evaluation of sulfur-bridged thiazole-, thiadiazole-, and triazine-based heterocyclic scaffolds

The development of structurally diverse heterocyclic frameworks remains a cornerstone in the search for new antimicrobial agents. In this work, four sulfur-bridged heterocyclic scaffolds (S1–S4) featuring thiazole, thiadiazole, pyridine, and triazine cores were synthesized using a one-pot base-promoted nucleophilic substitution strategy facilitated by phase-transfer catalysis. Structural elucidation was achieved using spectroscopic techniques, including FT-IR, UV-Visible, 1H,13C NMR, and ESI mass spectrometry. Single-crystal X-ray diffraction data for scaffold S4 confirmed its symmetrical, rigid architecture. The electronic absorption spectra revealed dominant π → π* transitions, consistent with high molecular planarity and delocalized electronic systems. Further insight into the electronic properties of S4 was obtained through density functional theory (DFT) calculations, which supported its extended conjugation and electron-donating potential. Antibacterial studies showed all scaffolds displayed varying inhibition against both Gram-positive and Gram-negative strains, with S4 consistently exhibiting the largest inhibition zones. Although Ciprofloxacin exhibited larger inhibition zones, the consistent measurable activity of S4 highlights it as a promising lead scaffold for future antibacterial development. The favorable performance of S4 is attributed to its highly conjugated structure and physicochemical properties, underscoring the importance of scaffold design in medicinal chemistry. Future molecular docking studies will be undertaken and correlated with in vitro antibacterial results to provide deeper insights into binding interactions and structure–activity relationships.