Synthesis, Characterization, and Antibacterial Evaluation of a Chromium(III) Schiff Base Complex Derived from Trimethoprim and Benzaldehyde

Abstract

The escalating global crisis of antimicrobial resistance (AMR) necessitates the development of novel therapeutic agents with improved efficacy and alternative mechanisms of action. In this study, a Schiff base ligand derived from trimethoprim (TMP) and benzaldehyde (BADA), designated TMP-BADA, together with its chromium(III) complex [Cr(TMP-BADA)Cl], was successfully synthesized and evaluated for antibacterial activity. TMP-BADA was obtained as a brown amorphous solid with a yield of 72% and a melting point of 278–280 °C, while the Cr(III) complex was isolated as a green powder in 80% yield with a decomposition temperature of 268–270 °C. Spectroscopic characterization by FT-IR and ¹H NMR confirmed Schiff base formation and metal coordination. The disappearance of the aldehydic ν(C=O) band of benzaldehyde at 1700 cm⁻¹ and the appearance of a new azomethine ν(C=N) band at 1655 cm⁻¹ confirmed imine formation, while coordination to Cr(III) was evidenced by a shift of the ν(C=N) band to 1621 cm⁻¹ together with perturbations in ν(N–H) and ν(C–O–C) vibrations. The antibacterial activities of TMP-BADA and [Cr(TMP-BADA)Cl] were evaluated against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus using agar well diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays. TMP-BADA exhibited zones of inhibition of 32, 35, and 30 mm against E. coli, P. aeruginosa, and S. aureus, respectively, while the Cr(III) complex produced inhibition zones of 27, 40, and 31 mm, respectively. Notably, the Cr(III) complex demonstrated enhanced activity against P. aeruginosa compared with chloramphenicol (40 vs. 32 mm). MIC values ranged from 50–100 mg/mL for TMP-BADA and 50–100 mg/mL for the Cr(III) complex, whereas MBC values ranged from 100–200 mg/mL. The findings demonstrate that Schiff base derivatisation of trimethoprim combined with transition metal complexation represents a promising strategy for the development of novel metallo-antibacterial agents with enhanced activity against resistant bacterial pathogens