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Trimethoprim (TMP) is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections. It belongs to the class of chemotherapeutic agents known as dihydrofolate reductase inhibitors. Its use is associated with idiosyncratic reactions, including liver toxicity and agranulocytosis. In order to determine TMP electrochemically, a metalloporphyrin modified glassy carbon electrode was prepared by coating [5,10,15,20- tetrakis(4-methoxyphenyl) porphyrinato]Mn (III)chloride (TMOPPMn(III)Cl) solution on the surface of the electrode. The electrochemical behaviour of TMP in Phosphate buffer solution (PBS) on TMOPPMn(III)Cl modified glassy carbon electrode (TMOPPMn(III)Cl/GCE) was explored using differential pulse voltammetry (DPV). The voltammograms showed enhanced oxidation response at the TMOPPMn (III)Cl/GCE with respect to the bare GCE for TMP, attributable to the electrocatalytic activity of TMOPPMn(III)Cl. Electrochemical parameters of the oxidation of TMP on the modified electrode were analyzed. The electro-oxidation of TMP was found to be irreversible, pH dependent and adsorption controlled on the modified electrode. It is found that the oxidation peak current is proportional to the concentration of TMP over the range 6 × 10⁻⁸ - 1 × 10⁻⁶ M with a very low detection limit of 3 × 10⁻⁹ M at 2 min open circuit accumulation. The repeatability expressed as relative standard deviation (RSD) for n = 9 was 3.2% and the operational stability was found to be 20 days. Another striking feature is that equimolar concentration of sulfamethoxazole did not interfere in the determination of TMP. Applicability to assay the drug in urine and tablet samples has also been studied.

The electrocatalysis of [5,10,15,20-tetrakis(4-methoxyphenyl)porphyrinato]Mn(III)chloride (TMOPPMn(III)Cl) toward the oxidation of trimethoprim was investigated by electrochemical and computational methods. Voltammetric analysis demonstrates the ability of TMOPPMn(III)Cl to act as an electrocatalyst for the oxidation of trimethoprim. DFT calculations were performed at the B3LYP level to detect the site of oxidation as well as to survey the role of manganese porphyrin in the facile oxidation of trimethoprim. Quantum chemical calculations affirm that the deprotonation of NH2 attached to C4 is more energetically favorable as compared to deprotonation of the C2 amino group. Also, the deprotonation of trimethoprim in the TMOPPMn(III)Cl-catalyzed reaction results in the formation of a more stable anion as compared to the uncatalyzed reaction. Atoms in molecule (AIM) analysis and natural bond orbital (NBO) analysis also substantiate the utility of TMOPPMn(III)Cl in trimethoprim oxidation by confirming the coordination of trimethoprim to manganese porphyrin on removal of proton.

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