Green Synthesis, Spectroscopic Characterization, and Structure–Activity Relationship of Novel Manganese–Benzamide Complexes with Antibacterial Activities

Abstract

GRAPHICAL ABSTRACT

The development of novel metal-based antimicrobial agents has emerged as an effective strategy to combat the growing challenge of antimicrobial resistance and biofilm-associated infections. In the present study, a series of novel manganese–benzamide coordination complexes were synthesized through an environmentally friendly synthetic approach and comprehensively characterized using Fourier-transform infrared (FT-IR), ultraviolet–visible (UV–Vis), proton and carbon nuclear magnetic resonance (¹H and ¹³C NMR), and elemental analyses to confirm their molecular structures and coordination behavior. The antibacterial potential of the synthesized complexes was systematically evaluated against representative Gram-positive and Gram-negative bacterial pathogens using multiple microbiological assays, including biofilm inhibition, time-kill kinetics, minimum bactericidal concentration (MBC), and shake-flask quantitative bacterial reduction methods. The synthesized manganese complexes demonstrated enhanced antibacterial efficacy compared with their corresponding free ligands, suggesting that metal coordination significantly improved their biological performance. The complexes effectively inhibited bacterial biofilm formation, exhibited concentration- and time-dependent bactericidal activity, and produced substantial reductions in viable bacterial populations under dynamic culture conditions. The improved biological activity is attributed to increased lipophilicity, enhanced membrane permeability, and synergistic interactions between the manganese ion and the benzamide ligand following chelation. Collectively, the findings demonstrate that manganese coordination considerably enhances the antimicrobial properties of benzamide derivatives and highlights the potential of these coordination compounds as promising candidates for the development of next-generation topical antibacterial agents for the prevention and management of bacterial and post-surgical wound infections. Further mechanistic investigations, cytocompatibility studies, and In Vivo evaluations are warranted to validate their clinical applicability.