Oxidative degradation of norfloxacin by a lipophilic oxidant, cetyltrimethylammonium permanganate in water–acetonitrile medium: A kinetic and mechanistic study

Abstract

The present study reports the oxidative metabolism of an established antibacterial drug norfloxacin (NRF) by a lipid compatible lipophilic Mn(VII) oxidant, cetyltrimethylammonium permanganate (CTAP) in acetonitrile–water binary mixture in the presence of acetic acid. The metabolized products are identified as 7-amino-1-ethyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, formaldehyde, and ammonia. The kinetics of the reaction is studied in aqueous acetonitrile media in the presence of acetic acid by UV–vis spectroscopic method by monitoring the absorbance of Mn(VII) at 530nm under pseudo first-order condition. The reaction is found to be first-order with respect to CTAP and fractional order with respect to norfloxacin and acetic acid. Occurrence of Michaelis–Menten type kinetics with respect to norfloxacin confirmed the binding of oxidant and substrate to form a complex before the rate determining step. A suitable ionic mechanism is proposed based on the experimental findings. The proposed reaction mechanism is supported by the effect of solvent polarity and effect of temperature on the reaction rate. High negative entropy of activation (ΔS≠=−259 to −158JK−1mol−1) supported the existence of a forced, more ordered and extensively solvated transition state. Further, solvent polarity–reactivity relationship revealed (i) the presence of less polar transition state compared to the reactants, (ii) differential contribution from dipolar aprotic (acetonitrile) and polar protic (water) solvents toward the reaction process through specific and nonspecific solute–solvent interaction and (iii) presence of intramolecular H-bonding in oxidant–substrate complex in acetonitrile rich domain and intermolecular H-bonding between oxidant–substrate complex and water in water rich domain.