Electron Transfer Processes in the Reactivity of Nonsteroidal Anti-inflammatory Drugs in the Ground and Excited States

Abstract

The nonsteroidal anti-inflammatory drugs (NSAID), naproxen, sulindac and indomethacin, were shown to donate electrons to nitro blue tetrazolium (NBT) when irradiated with UV light in deoxygenated aqueous buffer solution (pH 7.4, 30 degrees C). The reaction was monitored spectrophotometrically by the appearance of the diformazan reduction product from NBT. The electron transfer process facilitates the decomposition of the drugs. Naproxen in the presence of NBT is photodegraded principally to the alcohol (2-[1-hydroxyethyl]-6-methoxynaphthalene) at a rate approximately 20-fold faster than when irradiated alone in deoxygenated conditions. The photoproduct from naproxen also participates in the electron transfer to NBT but at a much slower rate than naproxen. Irradiation of sulindac or indomethacin in the presence of NBT caused the slow photoreduction of NBT to diformazan. In the absence of NBT, indomethacin and sulindac are essentially unreactive when irradiated in aqueous solution. The ability of a number of NSAID to act as electron donors in their ground state was studied by observing their oxidation by potassium peroxodisulfate in pH 7.0 phosphate buffer at 50 degrees C. The HPLC analysis of the drug remaining showed that the 2-arylpropionic acid NSAID (naproxen, ibuprofen, ketoprofen and suprofen) reacted at a rate equivalent to the thermal decomposition of peroxodisulfate. The major products were the same as detected in the photooxidation of these drugs, resulting from decarboxylation and oxygen addition but also included a dimeric compound. On the other hand, the NSAID that do not contain the propionic acid substituent all reacted more slowly with peroxodisulfate, enabling specific reaction rate constants to be evaluated.

Photoreactivity of the Nonsteroidal Anti-inflammatory 2-Arylpropionic Acids with Photosensitizing Side Effects¶

“…On the other hand, photoproducts NP4 and NP5 may be formed by nucleophilic trapping of the cationic intermediate NP-III (48,52). In this context, the ability of NP to act as an electron donor from its excited states has been demonstrated by the use of nitro blue tetrazolium as acceptor (53). Besides, NP undergoes oxidative decarboxylation chemically by treatment with oxidizing agents such as Ce (IV) or potassium peroxodisulfate, giving product patterns that can be explained through intermediates NP-I, -II, -III, -IV and -V (54).…”