This thesis relates the physicochemical properties of phenolic compounds to their antioxidant activities. It focuses on the partitioning of phenolic compounds between hydrophilic and lipophilic environments and the relevance this has to their in vivo health effects. Data in the literature was lacking so the phase partition coefficients (log P) of 53 phenolic antioxidants were measured by reversed-phase HPLC and calculated by log P prediction software. There was a very strong linear correlation between measured and calculated values (r=0.91). The importance of log P in determining antioxidant assay values was then tested by developing an assay system capable of measuring activities of both hydrophilic and lipophilic antioxidants. This Lipid Peroxidation Inhibition Capacity Assay (LPIC), based on using liposomes to simulate a cell membrane environment, was then used to measure the activity of antioxidants with a broad range of structures. The activities were correlated against log p, the difference of heat of formation (∆Hf) and half-wave potential (Ep/2) and used to derive a predictive model to calculate the LPIC activity. There was a highly significant linear correlation between the calculated and measured values. The LPIC activities also correlated well to published LDL inhibition activities but not to measured ORAC activities. These findings suggested that behaviours of antioxidants in the small unilamellar vesicles of the LPIC assay were similar to that in the LDL assay but not to the aqueous phase based ORAC assay. The LPIC assay may therefore be a better indicator of potential health benefits of antioxidants in the human body than the ORAC assay. The possible mechanistic reasons are that it may better reflect ability to prevent the oxidation of LDL blood stream particles that leads to cardiovascular disease and also takes into account the importance of membrane solubility which can raise the cellular concentration and thus potential to protect cells from oxidative damage. KEYWORDS: LPIC, LDL; Antioxidant; Phytochemical; Polyphenolic; Phenolic acid; Flavonoids; log P; Partition Coefficient; Liposome; Lipid bilayer; Lipid Membrane; ORAC; Comet assay; Flow Cytometry.
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