Antioxidant Free Radical Scavenging Mechanism And Structure - Activity Relationship Of Theory

In view of the importance of free radicals, the researches for high efficient, low-toxic and inexpensive antioxidants have been one of the substantial subjects in many fields such as biology, chemistry and medicine. Due to the feasibility of theoretical study of antioxidants, this thesis investigated the radical-scavenging mechanism of antioxidants, summarized the structure-activity relationship of antioxidants by quantum-chemical computational method. This provided a theoretical basis for searching and designing novel antioxidants, as well as screening of antioxidants and enriching of the species of antioxidants.The main results achieved by density functional theory (DFT) :1) Structure-activity relationship of traditional antioxidantsThe flavonoid-derived isoflavonoids, genistein and 4-thiaflavans were investigated. The results approved that the active center for genistein to scavenge peroxyl radical was B-ring, and this was consistent with the experimental finding. 5-OH of 4-thiaflavans played key role in enhancing the antioxidant activity of A-ring. The calculated BDEs gave a reasonable explanation on the DPPH radical-scavenging activity difference of 4-thiaflavans.2 ) Structure-activity relationship of indolinonic hydroxylamines and aminoxylsThe role of indolinonic hydroxylamines in protecting lipids from oxidation is comparative to a- tocopherols (a-T). The O-H BDEs revealed that hydroxylamine was the key structural factor for this type of antioxidants, and substituents had little effect on its activity. The variations of free energy (AG) for the coupling reactions and other physico-chemical parameters revealed the coupling site was determined by the property of trapped radical, and the radical-coupling activity difference between aminoxyls arised from the electronic properties of substituents. To elucidate the different lipid-oxidation potentials of aminoxyl antioxidants, the C-H bond dissociation enthalpies (BDEs) of a model linoleic acid (LH) and O-H BDEs of hydrogenated aminoxyls were calculated. The higher the O-H BDE of IHs was, the stronger the prooxidant activity of aminoxyl, and the different O-H BDEs of IHs were further clarified in terms of distinct electronic effects of the substituents.3 ) Investigation into the antioxidant activity of heterocyclic compoundsThe C-H bonds of heterocyclic compounds investigated in this thesis have ratherhigh antioxidant activity. The radical-scavenging mechanism of edaravone is one-step H-donation reaction, the active center is 2-pyrazolin-5-one; the active site is the C-H bond at 4-position; and the effect of substituent is negligible. 1, 4-dihydropyridine is an excellent lead antioxidant, which inspired us to have designed more promising antioxidant 2, 6-diethoxycarbonyl-l, 4-dihydropyridine theoretically.