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.