Girard's Reagent P Derivative of β-Apo-8′-carotenal: A Potent Photoprotective Agent†¶

Abstract

A cationic carotenoid derivative (GRP‐carotenal) was synthesized by the reaction of Girard's reagent P and β‐apo‐8′‐carotenal. The singlet‐oxygen quenching constants for GRP‐carotenal were 1.3 ± 0.1 × 1010 and 1.0 ± 0.1 × 1010M−1 s−1 in acetonitrile and in detergent micelles, respectively. Photosensitized damage to K562 leukemia cells from cis‐di(4‐sulfonatophenyl)diphenylporphine, hypericin and protoporphyrin IX was inhibited by GRP‐carotenal under conditions where β‐apo‐8′‐carotenal, β‐carotene and crocetin were ineffective. The unique cytoprotective properties of GRP‐carotenal, relative to the other carotenoids studied, could not be explained by the differences in the cell content of the various carotenoids or by the changes in the cell content of the photosensitizers used. Photosensitizer fluorescence from labeled K562 cells was reduced by GRP‐carotenal but not by the other carotenoids studied. The novel photoprotective properties of GRP‐carotenal may be due to its subcellular distribution. In photosensitizer‐containing detergent micelles, novel properties of GRP‐carotenal were not apparent. None of the carotenoids studied reduced photosensitizer fluorescence or singlet‐oxygen generation. Singlet‐oxygen quenching by GRP‐carotenal and by β‐apo‐8′‐carotenal were roughly the same. Crocetin has a singlet‐oxygen quenching constant that is about a factor of five lower. Singlet‐oxygen quenching by β‐carotene was limited by its aggregation.

Quenching of Singlet Oxygen by a Carotenoid–Cyclodextrin Complex: The Importance of Aggregate Formation

“…The relationship between the charge on the surface of the micelles and the extent of carotenoid aggregation likely applies only to carotenoids with ionized groups at both ends. The absorption of spectrum of the Girard’s reagent P derivative of β‐apo‐8′‐carotenal, a carotenoid closely related to (GRP) 2 ‐canthaxanthin, but with only one positive charge, appears to show no aggregation at all in CTAB micelles (5).…”

Structural Requirements for Efficient Cellular Photoprotection by Carotenoid Derivatives¶†

“…The synthesis, purification and structural confirmation of the Girard's reagent P (GRP) derivative of β‐apo‐8′‐carotenal ( trans ) (GRP‐carotenal) have been described previously ( 1 ).…”

“…Previously, we found that a synthetic cationic carotenoid derivative prevented photosensitized damage to K562 leukemia cells more effectively than three natural carotenoids that were either uncharged or negatively charged ( 1 ). One hypothesis that could explain the enhanced photoprotection provided by the cationic carotenoid derivative was that the derivative concentrated in mitochondria, more effectively prevented mitochondrial damage than natural carotenoids.…”

“… Abstract We have synthesized five carotenoid derivatives: ( 1 ) Girard's reagent P (GRP)‐retinal from GRP and retinal; ( 2 ) GRP‐carotenal from GRP and β‐apo‐8′‐carotenal; ( 3 ) Girard's reagent T (GRT)‐carotenal from GRT and β‐apo‐8′‐carotenal; ( 4 ) (GRP) 2 ‐canthaxanthin from 2 mol of GRP and 1 mol of canthaxanthin; and ( 5 ) dansyl hydrazine (DH)‐carotenal from DH and β‐apo‐8′‐carotenal. The first three derivatives are cations, whereas the fourth is a dication and the fifth is a weak base.…”

Synthesis and Antimicrobial Study of Novel 1‐Benzylated Water‐Soluble Isatin‐3‐hydrazones

“…Their high reactivity towards carbonyl compounds has been successfully used in mass‐spectrometric determination of steroids in biological samples. [ ][ ] In addition, it is known that a number of acylhydrazones on the base of Girard's reagents and their metal complexes exhibit a wide range of biological activity …”