Certain drugs can photosensitive the formation of protein modifications, which are thought to be responsible for the occurrence of photoallergy. In the present work, the UV irradiation of serum albumin in the presence of tiaprofenic acid has been studied as a model system for drug-photosensitized protein modifications. The photolysates evidenced that His, Tyr, and Trp are the reactive sites of the protein. The experimental results strongly suggest that formal hydrogen abstraction from the OH or NH groups of Tyr or Trp by the excited drug is the key photochemical process. Competition between cage escape and in cage recombination of the resulting radical pairs governs the final outcome: protein photo-cross-linking versus drug-protein adduct formation. These findings are highly relevant to understand the process of photohapten formation, the first event in the onset of photoallergy.

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The photodegradation of Ibuprofen, a widely used non‐steroidal anti‐inflammatory drug (NSAID), was examined. Several photoproducts (I‐VI) were isolated and identified on the basis of their IR‐1H‐NMR‐ and 13C‐NMR‐ spectra. The chemical structures were confirmed by unambiguous alternative synthesis from available reagents. The most significant primary photochemical process was the cleavage of the C‐C bond a to the carboxy group. Subsequent secondary processes (hydrogen abstraction, dimerization, incorporation of methanol, or reaction with oxygen) might account for the formation of the different photoproducts. The cytotoxic effects were assayed using the red‐blood cell lysis test and the enzyme leakage (LDH and GOT) from cultured fibroblasts. Compound V [l‐(4 isobutylphenyl)‐ethanol] was found to be toxic for both system at concentrations greater than 1 mM while compound IV [l‐(4 isobutylphenyl acetophenone)] was toxic for fibroblasts but not for erythrocytes at the same concentration. Ibuprofen and the other photocompounds were apparently non‐toxic. The significance of these results is discussed in connection with the possible in vivo phototoxicity of Ibuprofen.

Three model dyads have been synthesized by esterification of beta- and alpha-cholesterol (Ch) with (S)- and/or (R)-ketoprofen (Kp). The alpha-dyads are efficient photogenerators of the 7-allyl Ch radicals by intramolecular H abstraction. Subsequent cyclization via C-C coupling occurs in a stereoselective way.