Acetazolamide as a singlet molecular oxygen quencher

Abstract

According to literature the acetazolamide, which is commonly used as a diuretic, shows phototoxic properties. To contribute to the understanding of the role of this chemical as a generator of the very common toxic substance, the singlet molecular oxygen, O 2 ( 1 Δ g ), in this paper we show a kinetic study about the photosensitized oxidation of acetazolamide and its photosensitizing nature in the generation of O 2 ( 1 Δ g ). Contrary to our expectations, results show that this drug has a predominant activity as an O 2 ( 1 Δ g ) deactivator and its ability to generate the singlet oxygen is small. To find the mechanism of this activity, chemical reactivity constants measured in several solvents were adjusted to first-order kinetics. We found very moderate values around 10 5 M -1 s -1 , which compared to the total rate, the sum of the physical and chemical rate constants, of around 10 7 M -1 s -1 , supports a physical type of quench as the main acetazolamide deactivation pathway of O 2 ( 1 Δ g ). Additionally, due to a moderate solvent effect of the reaction between acetazolamide and O 2 ( 1 Δ g ) it is possible to postulate the formation of an exciplex complex with small charge separation. Finally, quantum yield values for the generation of singlet oxygen, determined through steady-state experiments, are 0.056, 0.097, and 0.015 in methanol, ethanol, and acetonitrile, respectively. Therefore, we can conclude that acetazolamide is an efficient quencher of singlet molecular oxygen (mainly of the physical type) and its phototoxic activity may involve other species different from singlet oxygen.