Predicting how polyphenol antioxidants prevent DNA damage by binding to iron.
Prevention of oxidative DNA damage due to hydroxyl radical is important for the prevention and treatment of disease. Because of their widely recognized antioxidant ability, 12 polyphenolic compounds were assayed by gel electrophoresis to directly quantify the inhibition of DNA damage by polyphenols with Fe(2+) and H2O2. All of the polyphenol compounds have IC50 values ranging from 1-59 microM and inhibit 100% of DNA damage at 50-500 microM concentrations. Gel electrophoresis results with iron(II)EDTA and UV-vis spectroscopy experiments confirm that binding of the polyphenol to iron is essential for antioxidant activity. Furthermore, antioxidant potency of polyphenol compounds correlates to the pKa of the first phenolic hydrogen, representing the first predictive model of antioxidant potency based on metal-binding. Understanding this iron-coordination mechanism for polyphenol antioxidant activity will aid in the design of more-potent antioxidants to treat and prevent diseases caused by oxidative stress, and help develop structure-activity relationships for these compounds.
Perron
Nathan R
NR
Department of Chemistry, Clemson University, Clemson, South Carolina 29634-0973, USA.
Hodges
James N
JN
Jenkins
Michael
M
Brumaghim
Julia L
JL
D000975:Antioxidants / Q000737:chemistry*; D004249:DNA Damage; D005419:Flavonoids / Q000737:chemistry*; D006860:Hydrogen Bonding; D007501:Iron / Q000737:chemistry*; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry*; D059808:Polyphenols
D000975:Antioxidants; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D007501:Iron