Acetazolamide as a singlet molecular oxygen quencher

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, O2(1Δg), in this paper we show a kinetic study about the photosensitized oxidation of acetazolamide and its photosensitizing nature in the generation of O2(1Δg). Contrary to our expectations, results show that this drug has a predominant activity as an O2(1Δg) 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 105 M−1 s−1, which compared to the total rate, the sum of the physical and chemical rate constants, of around 107 M−1 s−1, supports a physical type of quench as the main acetazolamide deactivation pathway of O2(1Δg). Additionally, due to a moderate solvent effect of the reaction between acetazolamide and O2(1Δg) 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.

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► Acetazolamide is capable of efficiently quenching singlet oxygen through a physical-type mechanism.
► Acetazolamide is a photosensitizer of weak singlet oxygen production.
► It is possible that the adverse side effects of acetazolamide are not caused by a type II mechanism.
► It is possible to suggest the formation of the exciplex complex with small charge separation, between thiadiazol in acetazolamide and singlet oxygen.