Development of novel antioxidants: design, synthesis, and reactivity.
We are attempting to develop novel synthetic antioxidants aimed at retarding the effects of free-radical induced cell damage. In this paper we discuss the design strategy and report the synthesis of seven novel antioxidants, including six catechols and a benzylic phenol. The bond dissociation enthalpy (BDE) for the most active (weakest) OH bond in each molecule was calculated by theoretical methods, as well as the BDE for the semiquinone radical. Reaction rates with the nitrogen-centered free radical DPPH(*) were measured in ethyl acetate. The log of k(DPPH) for bimolecular reaction correlated well with the primary BDE. The correlation between rate constants and calculated BDEs shows that the BDE is a good predictor of antioxidant activity with DPPH(*), suggesting that our design criteria are useful and that these compounds should undergo further testing in cell cultures and in animal models.
Hussain
Helmi H
HH
Department of Chemistry, University of Ottawa, D'Iorio Hall, 10 Marie Curie Street, Ottawa, Canada K1N 6N5.
Babic
Gordana
G
Durst
Tony
T
Wright
James S
JS
Flueraru
Mihaela
M
Chichirau
Alexandru
A
Chepelev
Leonid L
LL
D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry; D001713:Biphenyl Compounds; D002396:Catechols / Q000737:chemistry; D015195:Drug Design; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D009281:Naphthalenes / Q000737:chemistry; D010851:Picrates / Q000737:chemistry; D013816:Thermodynamics
D000975:Antioxidants; D001713:Biphenyl Compounds; D002396:Catechols; D007202:Indicators and Reagents; D009281:Naphthalenes; D010851:Picrates; C004931:1,1-diphenyl-2-picrylhydrazyl