Structure Modification And Mechanisim Of Phenolic Antioxidants

ROS (reactive oxygens pecies) have pros and cons for human health. In healthy subject, there is a tightly controlled balance between the generation and removal of ROS. Excissive production of ROS plays an important role in cancer, aging and several degenerative diseases. Plant and food-derived antioxidants have beneficial effect in protecting against these diseases. Thus, development of highly efficient antioxidants has attracted many scientists'attention.In this article, we synthesized a series of curcumin analogues, studied and compared the capacity of curcumin-directed analogues to scavenge 2,2-diphenyl-l-picrylhydrazyl (DPPH·) and protect human red blood cells (RBCs) from oxidative haemolysis to investigate the structure-activity-relationship; The radical-scavenging activity and detailed mechanism of resveratrol analogues and hydroxyl-chalcones were investigated by the reaction kinetics with galvinoxyl (GO·) and 2,2-diphenyl-l-picrylhydrazyl (DPPH·) radicals in different solvents (ethanol, methanol and ethyl acetate) at 25℃, using UV-vis spectroscopy; Besides, we also examined the activity of hydroxyl-chalcones against free radical (AAPH) mediated DNA strand breakage and curcuminoids Knoevenagel condensates antiproliferative effect on human promyelocytic leukemia cells (HL-60). To interpret the structure-activity-relationship and antioxidant mechanism of hydroxyl-chalcones with the asymmetrical structures, we also calculated O-H bond dissociation enthalpy (BDE).The results revealed that: 1) The curcumin analogues which bear o-diphenoxyl and o-dimethoxyphenoxyl hydroxylgroups exhibited significantly higher DPPH·-scavenging and anti-haemolysis activitiesthan those which bear no such groups. In contrast to curcumin analogues that retainedthe 7-carbon spacer, the compounds with a 5-carbon linker had lower activity. In thecase of the latter, the introduction of ring further decreased DPPH·-scavenging activity.However, the introduction of ring did increase anti-haemolysis activity, suggesting thatthe lipophilicity of these compounds might play an important role in the antioxidantactivity. 2) The measured rate constants for radical-scavenging reaction of phenolic antioxidants(resveratrol analogues, hydroxyl-chalcones as well as hydroxycinnamic acid derivatives) revealed that in supporting ionization solvents (Methanol, ethanol) besides hydrogen atom transfer (HAT), the kinetics of the process was partially governed by sequential proton loss electron transfer (SPLET). The relatively low rate constants for the reactions of ArOHs with radical in ethyl acetate compared with the rate constants in ethanol proved that in ethyl acetate these reactions occured primarily by the HAT mechanism.3) These compounds of resveratrol analogues, which have electron-donating groups (-OH,-OCH3) in the ortho-or para-position of 4-OH exihibited significantly higher antioxidant activity, but which have electron-withdrawing groups (-NO2,-CF3) exihibited opposite results.4) Radical-scavenging rate constants of hydroxycinnamic acid derivatives were self-inhibited in methanol for their acidity.5) The results of hydroxyl-chalcones from experiments were agreed with that from theoretical calculation (BDE), and the structure-activity-relationship analysis was further elucidated.6) Curcuminods Knoevenagel condensates showed more effective cytotoxicity than the precursor.