Isolation of cross-coupling products in model studies on the photochemicalmodification of proteins by tiaprofenic acid

To gain insight into the chemical nature of drug-induced photoallergy, mode l studies have been carried out on the photochemical modification of protei ns by tiaprofenic acid. Irradiation of decarboxylated tiaprofenic acid (DTP A) in the presence of p-cresol leads to C-C- and C-O-connected p-cresol "di mers", together with DTPA hydrodimers. The p-cresol-DTPA cross-coupling pro duct was not detected in this reaction. However, a product of this type is formed using a more hindered phenol, such as 2,6-di-tert-butylphenol. Simil ar results are obtained when tiaprofenic acid (TPA) or its methyl eater are used as photosensitizers. The observed formation of "dimers" can be relate d to protein photocrosslinking, through the coupling of two tyrosine units. On the other hand, phenol-(D)TPA cross-coupling may be relevant to the und erstanding of drug-protein photobinding.