Phenolic Antioxidants, Free Radical Scavenging Role Of Quantitative Structure-activity Relationship Study

As free radicals cause degradation of many industrial materials, degeneration of foods, and sorts of disease, such as inflammation, nearodegeneration, and tumors, selecting highly efficient antioxidants with low toxicity has been paid much attention. Due to the wide use of phenolic antioxidants, the mechanism of antioxidant scavenging free radicals and a preliminary structure-activity relationship are obtained. This will be helpful in order to further the study in this field and accelerate the selection of antioxidants. Theoretical parameters characterizing the antioxidant activity are calculated using quantum chemical ab initio and other physical chemical methods, and the quantum structure-activity relationship is constructed together with the experimental antioxidant activities using the symbolic statistic method. Structure factors effectuating the theoretical parameters are further elucidated. The important and valuable results in this thesis can be summarized as follows. 1. Transition StateS for free radical with phenolic compounds have been calculated using high-level ab initio method. The parameters including barrier, atom net charge, dipole et al are obtained. Compared with the experimental values, the hydrogen abstraction reaction mechanism has been revealed. 2. The selection and calculation of Theoretical physicochemical parameters scavenging activity on alkyl, alkoxyl, alkyl peroxyl radicals (R, R0, R00) The static molecular parameters including 0-H bond length, 0-H bond order, 0-H Mul[iken population, 0-H charge difference, 0-H bond stretching force constant (k) and highest occupied molecular orbital energy level (EHOMO) for series of phenols have been calculated by ab 77 inhtio. In combination with the logarithm of free radical scavenging rate constant, it is found that 0-H BDE is a good parameter characterizing scavenging free radicals. Although EHOMO can measure the 0-H BDE for simple phenols, they are invalid when the phenols possess intramolecular hydrogen bond. Other static 0-H bond parameters are ineffective for characterizing antioxidant activity. Because the molecular lipophilicity parameter (log P) and solvent-accessible surface of hydroxyl hydrogen (H-sttrf) can also effect the scavenging activity, in this paper, the theoretical index for QSAR includes 0-H BDE, log P, H-surf, and EHQ~1O. 3. QSAR rhodels for antioxidants Using pertinence analysis, theoretical parameters including 0桯 BDE, EHOMO, lOgPMLP~ H桽urf together with percent inhibition of lipid peroxidantion ( LP%) establish quantum structure-activity relationship, namely, QSAR models. The best equation is LP%~-4,44X b~ H,,0. +6.57X logPMLp?17.73EH0M0+l.l63XHSurf 102.23, R~0.93. 4. Substituente effects determining 0-H BDE of phenolic compounds The substituent effects, including electronic effect and intramolecular hydrogen bond (II-IB) effect, on 0-H bond dissociation energy (BDE) of phenolic compounds have been investigated by a density functional theory (DFT) using the 6~31G** basis set. For para substituted monophenols, the stability of phenoxy radical (SPR), the stability of parent molecule (SPM) and the relative 0-H BDE correlate well with + Hammett-type parameter a~ and...