Crystal and molecular structure of piceatannol; scavenging features of resveratrol and piceatannol on hydroxyl and peroxyl radicals and docking with transthyretin.
The mechanism by which the naturally occurring polyphenolic compounds resveratrol (RES), C(14)H(12)O(3), and its metabolite piceatannol (PIC), C(14)H(12)O(4), scavenge free radicals is studied using experimental and density functional theory (DFT) methods. PIC's crystal structure shows a strong intermolecular hydrogen bond network, which, through a concerted motion of the hydroxyl hydrogen atoms, can produce a second hydrogen bond chain. This reorganization offers a low-energy pathway for the transfer of hydrogen atoms and is a contributing factor to PIC's biological activity. Additionally, DFT calculations describing the entire reaction mechanism of RES, PIC, and 3,3',4',5,5'-pentahydroxystilbene with hydroxyl and peroxyl radicals agree with experimental results, showing that increased hydroxylation aids in scavenging activity. PIC is more efficient than RES because (i) by sharing its 3'-OH hydrogen atom with its adjacent neighbor, O-4', the abstraction and transfer of the 4'-H atom to the free radical becomes easier and (ii) the resulting PIC semiquinone radical is more stable. As a result of the reaction with OH(*), both RES and PIC form water; with the peroxyl radical, both RES and PIC form hydrogen peroxide. Also, docking of PIC onto the protein transthyretin suggests better performance than RES and confirms its possible application in neurodegenerative conditions such as Alzheimer's disease.
Rossi
Miriam
M
Department of Chemistry, Vassar College, Poughkeepsie, New York 12604-0484, USA. rossi@vassar.edu
Caruso
Francesco
F
Opazo
Cristian
C
Salciccioli
Justin
J
D003460:Crystallization; D018360:Crystallography, X-Ray; D016166:Free Radical Scavengers / Q000737:chemistry*; D006860:Hydrogen Bonding; D017665:Hydroxyl Radical; D015394:Molecular Structure; D010545:Peroxides; D011228:Prealbumin / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000378:metabolism
D016166:Free Radical Scavengers; D010545:Peroxides; D011228:Prealbumin; D013267:Stilbenes; C049375:perhydroxyl radical; D017665:Hydroxyl Radical; C041525:3,3',4,5'-tetrahydroxystilbene; D000077185:Resveratrol