5-S-lipoylhydroxytyrosol, a multidefense antioxidant featuring a solvent-tunable peroxyl radical-scavenging 3-thio-1,2-dihydroxybenzene motif.
5-S-Lipoylhydroxytyrosol (1), the parent member of a novel group of bioinspired multidefense antioxidants, is shown herein to exhibit potent peroxyl radical scavenging properties that are controlled in a solvent-dependent manner by the sulfur center adjacent to the active o-diphenol moiety. With respect to the parent hydroxytyrosol (HTy), 1 proved to be a more potent inhibitor of model autoxidation processes in a polar solvent (acetonitrile), due to a lower susceptibility to the adverse effects of hydrogen bonding with the solvent. Determination of O-H bond dissociation enthalpies (BDE) in t-butanol by EPR radical equilibration technique consistently indicated a ca. 1.5 kcal/mol lower value for 1 relative to HTy. In good agreement, DFT calculations of the BDEOH using an explicit methanol molecule to mimic solvent effects predicted a 1.2 kcal/mol lower value for 1 relative to HTy. Forcing the geometry of the -S-R group to coplanarity with the aromatic ring resulted in a dramatic decrease in the computed BDEOH values suggesting a potentially higher activity than the reference antioxidant α-tocopherol, depending on geometrical constrains in microheterogeneous environments. These results point to sulfur substitution as an expedient tool to tailor the chain-breaking antioxidant properties of catechol derivatives in a rational and predictable fashion.
Department of Chemistry "G. Ciamician", University of Bologna , Via S. Giacomo 11, I-40126 Bologna, Italy.
Riccardo
R
Amorati
Luca
L
Valgimigli
Lucia
L
Panzella
Alessandra
A
Napolitano
Marco
M
d'Ischia
D000975:Antioxidants / Q000737:chemistry*; D002396:Catechols / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000737:chemistry*; D006860:Hydrogen Bonding; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry*; D012997:Solvents; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D020002:tert-Butyl Alcohol / Q000737:chemistry*
C000589399:3-thio-1,2-dihydroxybenzene; D000975:Antioxidants; D002396:Catechols; D016166:Free Radical Scavengers; D010636:Phenols; D012997:Solvents; D013438:Sulfhydryl Compounds; C034221:catechol; D020002:tert-Butyl Alcohol