Kinetics and Mechanism of the Photosensitized Oxidation of Furosemide

Detection of O₂(¹Δ_g) phosphorescence emission, λ_max = 1270 nm, following laser excitation and steady-state competitive methods was employed to measure total rate constants, k_T, for the reactions of the diuretic furosemide, 2-methylfurane and furfurylamine with singlet oxygen in several solvents. Correlation of k_T values with solvent parameters and product identification shows that the reaction mechanism is strongly solvent dependent. In aliphatic alcohols, the dependence of k_T 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 k_T 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(¹Δ_g) by furosemide was detected. Quantum yields of 0.047 ± 0.003 and 0.078 ± 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.