Synthesis and Characterization of Metal Complexes as Potential Therapeutic Agents for Tuberculosis

Abstract

The rapid emergence of antimicrobial resistance necessitates the development of alternative therapeutic strategies, including metal‑based coordination compounds. This study reports the synthesis, characterization, computational evaluation, and biological assessment of six metal complexes derived from salicylic acid, succinic acid, and mixed salicylate–succinate ligands coordinated to iron(II) and silver(I). The complexes were characterized using Fourier‑transform infrared spectroscopy (FTIR), ultraviolet–visible (UV–Vis) spectroscopy, thermogravimetric analysis (TGA), powder X‑ray diffraction (PXRD), and X‑ray fluorescence analyses. Density functional theory (DFT) and time‑dependent DFT (TD‑DFT) calculations were performed to optimize geometries, support vibrational stability, and elucidate electronic transitions. Spectroscopic results supported coordination through oxygen donor atoms of the carboxylate and phenolic groups, while computational findings supported octahedral configurations for Fe(II) complexes and ligand‑dominated electronic structures for Ag(I) complexes consistent with their d¹⁰ configuration. Biological evaluation revealed a clear metal‑dependent structure–activity relationship: silver(I) complexes exhibited broad‑spectrum antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans, with the mixed‑ligand Ag(I) complex showing the highest potency, whereas iron(II) complexes displayed limited activity. Antitubercular screening using the Microplate Alamar Blue Assay (MABA) against Mycobacterium tuberculosis H37Rv showed potent inhibition by all Ag(I) complexes (MIC ≤ 0.125 mg/mL), while Fe(II) complexes were inactive. Coordination significantly enhanced the activity of salicylic acid relative to the free ligand, highlighting the importance of chelation in modulating biological efficacy. This study demonstrates that metal identity governs antimicrobial and antitubercular activity within the investigated ligand framework and identifies silver(I) coordination complexes as promising candidates for further development.