A Comparative Study of the Photochemistry of the Non‐steroidal Anti‐inflammatory Drugs, Naproxen, Benoxaprofen and Indomethacin

Abstract

Abstract— The photochemical reactivity of the non‐steroidal anti‐inflammatory drugs, naproxen and indomethacin, has been studied and compared with benoxaprofen, a similar compound of known cutaneous phototoxicity. Although indomethacin shows some phosphorescence at 77 K, flash photolysis at room temperature revealed only a weak photoionization process, and no photochemical reactivity was detected in steady state photolysis. Naproxen has strong fluorescence and phosphorescence, and in laser flash photolysis showed photoionization and a triplet state species in approximately equal yield. Naproxen and benoxaprofen produced singlet oxygen with similar quantum yield, as deduced from the sensitized rates of photooxidation of 2,5‐dimethylfuran. Naproxen underwent photodecarboxylation as detected by ESR‐spin trap experiments with 2‐methyl‐2‐nitrosopropane. The decarboxy‐naproxen radical combined readily with oxygen in aerated solution, and l‐(6‐methoxy‐2‐napthyl)ethanol and 2‐acetyl‐6‐methoxynaphthalene were formed as the oxidation products. In deaer‐ated solution, the major product was 2‐ethyI‐6‐methoxynaphthalene, with the alcohol also formed. In comparison, benoxaprofen also underwent decarboxylation, with much higher quantum yield, but the decarboxy‐benoxaprofen radical did not add oxygen. This difference in photoreactivity between naproxen and benoxaprofen, together with the much lower molar absorptivity of naproxen are the significant factors in relating to the differences in reported levels of clinical photosensitivity responses.

Photochemical fate of pharmaceuticals in the environment: Naproxen, diclofenac, clofibric acid, and ibuprofen

“…Because pharmaceuticals are released into surface waters via discharge of wastewater treatment plant effluent, photochemical processes may be an important removal process for these compounds. Much of the previous work on the photochemistry of naproxen and ibuprofen has focused on their phototoxicity (Castell et al, 1987;Moore and Chappuis, 1988;Bosca et al, 1990;Condorelli et al, 1993;Jimenez et al, 1997). The conditions of the studies varied widely (e.g., light source, wavelength cutoff, solvent) and have limited environmental relevance.…”

Aromatic Ketones as Photocatalysts: Combined Action as Triplet Photosensitiser and Ground State Electron Acceptor

“…These NP dimers have not been previously detected in other thermally or photochemically induced naproxen decarboxylations. [5,6,10] In summary, it is demonstrated that an aromatic ketone, such as 2-benzoylthiophene, can play a dual role: triplet photosensitiser and catalyst. This strategy has resulted in a new method for naphthylacetic acids decarboxylation.…”

“…The photosensitised NPCO 2 H conversion decreased when using deaerated solutions and 1:10 BT/naproxen molar ratio, and the only products were dimers 3 (1.4 %) and 2-ethyl-6-me- thoxynaphthalene [6] (3 %). By contrast, almost complete transformation of naproxen was achieved when using a 10:1 BT/ naproxen ratio under anaerobic conditions, whereby dimers 3 (27 %) and 6-methoxy-2-naphthylethane (9 %), together with BTH-NP cross-coupling products 4 (36 %) and BTH homodimers [9a] were obtained (Scheme 1).…”

“…Naphthylacetic acids, such as naproxen (NPCO 2 H, 2) or its salt (NPCO 2 À ), are known to photodecarboxylate via electron ejection, [5,6] but there is no report of the involvement of naproxen triplet excited state in such photooxidative process. [7] However, naproxen triplet could be decarboxylated in the presence of an adequate electron acceptor.…”

Supramolecular Interactions of Nonsteroidal Anti‐inflammatory Drug in Nanochannels of Molecular Containers: A Spectroscopic, Thermogravimetric and Microscopic Investigation

“…[31] Over the past few years, efforts have focussed on enhancing the solubility and bioavailability of the NSAID IMC molecule in different environments. [32][33][34][35][36][37][38][39][40][41][42][43][44][45] Most previous work has involved the formation of inclusion complexes between IMC with b-CD and its derivatives. [34,[37][38][39][40][41][42][43][44][45] It was found that complex formation between IMC and CDs depends on the method of preparation.…”