Synthesis, characterization, and direct aqueous superoxide anion scavenging of a highly water-dispersible astaxanthin-amino acid conjugate

Bioorg Med Chem Lett. 2004 Aug 2;14(15):3985-91. doi: 10.1016/j.bmcl.2004.05.038.


The aqueous solubility and/or dispersibility of synthetic carotenoid analogs can be improved by varying the chemical structure(s) of the esterified moieties. In the current study, a highly water-dispersible astaxanthin (3,3'-dihydroxy-beta,beta-carotene-4,4'-dione) derivative was synthesized by esterification to the amino acid L-lysine, and subsequently converted to the tetrahydrochloride salt. Deep violet, evenly colored aqueous suspensions were obtained with addition of the novel derivative to USP purified water up to a maximum of 181.6 mg/mL. These aqueous suspensions were obtained without the addition of heat, detergents, co-solvents, or other additives. At higher concentrations (above 181.6 mg/mL), the dispersion became turbid and viscous. There was no saturation point up to 181.6 mg/mL. The direct superoxide scavenging ability of the tetrahydrochloride dilysine astaxanthin salt was also evaluated by electron paramagnetic resonance (EPR) spectroscopy in a well-characterized in vitro isolated human neutrophil assay. The novel derivative was an extremely potent (micromolar concentration) aqueous-phase scavenger, with near-complete suppression of the superoxide anion signal (as detected by spin-trap adducts of DEPMPO) achieved at 100 microM. To the authors' knowledge, this novel carotenoid derivative exhibits the greatest aqueous dispersibility yet described for a natural and/or synthetic C40 carotenoid, and as such, will find utility in those applications for which aqueous-phase singlet oxygen quenching and direct radical scavenging are required.

MeSH terms

  • Amino Acids / chemistry
  • Amino Acids / pharmacology
  • Free Radical Scavengers / chemical synthesis*
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology*
  • Humans
  • In Vitro Techniques
  • Models, Molecular
  • Molecular Conformation
  • Neutrophils / drug effects
  • Neutrophils / physiology*
  • Solubility
  • Structure-Activity Relationship
  • Superoxides*
  • Xanthophylls
  • beta Carotene / analogs & derivatives*
  • beta Carotene / chemical synthesis*
  • beta Carotene / chemistry
  • beta Carotene / pharmacology


  • Amino Acids
  • Free Radical Scavengers
  • Xanthophylls
  • beta Carotene
  • Superoxides
  • astaxanthine