Kinetics and Mechanism of the Photosensitized Oxidation of Furosemide

Abstract

Detection of O,('A,) phosphorescence emission, A,,,, = 1270 nm, following laser excitation and steady-state competitive methods was employed to measure total rate constants, k,, for the reactions of the diuretic furosemide, 2- methylfurane and furfurylamine with singlet oxygen in several solvents. Correlation of k, values with solvent parameters and product identification shows that the reaction mechanism is strongly solvent dependent. In aliphatic alcohols, the dependence of k, on solvent parameters is similar to the one observed for triethylamine, suggesting a reaction mechanism involving partial charge transfer from the amino group to the singlet oxygen. In nonprotic solvents, the dependence of kT on solvent parameters resembles the behavior found for 2-methylfurane and furfurylamine, implying that mostly a 2 + 4 cycloaddition mechanism of singlet oxygen to furane ring of furosemide occurs in these solvents. These mechanistic differences are explained in terms of hydrogen-bonding interactions between the carboxylic group in the aromatic ring and the amino group of furosemide. Furthermore, direct generation of O2('Ag) by furosemide was detected. Quantum yields of 0.047 & 0.003 and 0.078 f 0.004 were determined in acetonitrile and benzene, respectively. This last result may be related, at least partially, to the photodynamic effects of this diuretic drug.