Girard's reagent P derivative of beta-apo-8'-carotenal: A potent photoprotective agent

A cationic carotenoid derivative (GRP-carotenal) was synthesized by the rea ction of Girard's reagent P and beta -apo-8 ' -carotenal. The singlet-oxyge n quenching constants for GRP-carotenal were 1.3 +/- 0.1 x 10(10) and 1.0 /- 0.1 x 10(10) M-1 s(-1) in acetonitrile and in detergent micelles, respec tively. Photosensitized damage to K562 leukemia cells from cis-di (4-sulfon atophenyl)diphenylporphine, hypericin and protoporphyrin IX was inhibited b y GRP-carotenal under conditions where beta -apo-8 ' -carotenal, beta -caro tene and crocetin were ineffective. The unique cytoprotective properties of GRP-carotenal, relative to the other carotenoids studied, could not be exp lained by the differences in the cell content of the various carotenoids or by the changes in the cell content of the photosensitizers used. Photosens itizer fluorescence from labeled K562 cells was reduced by GRP-carotenal bu t not by the other carotenoids studied. The novel photoprotective propertie s of GRP-carotenal may be due to its subcellular distribution. In photosens itizer-containing detergent micelles, novel properties of GRP-carotenal wer e not apparent. None of the carotenoids studied reduced photosensitizer flu orescence or singlet-oxygen generation. Singlet-oxygen quenching by GRP-car otenal and by beta -apo-8 ' -carotenal were roughly the same. Crocetin has a singlet-oxygen quenching constant that is about a factor of five lower. S inglet-oxygen quenching by beta -carotene was limited by its aggregation.