GREEN SYNTHESIS OF A NICOTINAMIDE-DERIVED SCHIFF BASE AND CONVENTIONALLY PREPARED METAL COMPLEXES FOR ANTIMICROBIAL ACTIVITIES

Abstract: Green synthesis of a novel nicotinamide-derived Schiff base ligand [N,N′-(Z)-1,4-phenylenebis(methaneylyidene)dinicotinamide] is reported via a catalyst-free aqueous route using water as a sustainable solvent. The transition metal complexes of this molecules were prepared with Mn(II), Fe(II), Co(II), Ni(II), Cu(II), and Zn(II) in good yields and characterized by FTIR, UV–Vis, NMR, HRMS, and LC-MS, confirming successful coordination through azomethine nitrogen and amide oxygen atoms. The biological activities of Schiff base and its transition metal complexes were systematically evaluated against Gram-positive and Gram-negative bacterial strains (E. coli, S. aureus, P. aeruginosa, E. faecalis) and fungal isolates (Candida albicans, C. glabrata). The Co(II) and Fe(II) complexes exhibited good antibacterial activities (MIC values 256–512 µg/mL), and the Fe(II) complex demonstrated the most promising antifungal activity (MIC 256 µg/mL against C. albicans). Notably, synergy studies revealed significant enhancement when combined with standard drugs: Compound 7 with fluconazole reduced MIC values fourfold against C. albicans (FICI = 0.18), while Co(II) complex with Ampicillin showed synergistic effects against E. coli (FICI = 0.50). These findings highlight the role of metal coordination in modulating antimicrobial activity and establish nicotinamide-based Schiff base complexes as potential scaffolds for the development of eco-friendly antimicrobial agents.