Photochemistry of 2,6-Dichlorodiphenylamine and 1-Chlorocarbazole, the Photoactive Chromophores of Diclofenac, Meclofenamic Acid and Their Major Photoproducts

Article abstract of DOI:10.1111/j.1751-1097.1998.tb02523.x

Diclofenac and meclofenamic acid are two structurally related nonsteroidal anti-inflammatory drugs with some photosensitizing potential. Their photochemistry involves cyclization to monohalogenated carbazoles. In principle, photocyclization could occur by photodehalogenation, followed by intramolecular radical addition, or by 6π electrocyclization and subsequent dehydrohalogenation of the intermediate dihydrocarbazoles. Previously, it has been assumed that the reaction follows the first pathway and that the key species associated with phototoxicity are the resulting aryl radicals. In the present work, we have performed photophysical and photochemical studies on 2,6-dichlorodiphenylamine (1a). This is a suitable model compound because since it contains the active chromophore present in diclofenac and meclofenamic acid, and its photoreactivity should be relevant to the understanding of the photobiological properties of both drugs. Our results clearly show that the first photochemical reaction is a very rapid 6π-electrocyclization, and hence no radicals are formed at this stage. Instead, cleavage of the carbon-halogen bond occurs in the 1-chlorocarbazole photoproduct 2a. The reduced lifetime of the 2a triplet (as compared with the unsubstituted carbazole) and the observed reaction quenching by oxygen are in agreement with the reaction occurring from the excited triplet state. Overall, the above results suggest that the potential phototoxicity of diclofenac and meclofenamic acid is due to a photobiologically active photoproduct that is able to generate radicals upon photolysis, rather than to the parent drug.