Studies On Antioxidants And Prooxidants Of -OH, -SH, -NH And C=C Compounds

In recent years, the investigation of antioxidants is one of the attractive topics in physical organic chemistry, the research usually focuses on the assessment of antioxidant properties and development of new antioxidants but neglect the safety of them. To this end, the research of antioxidants on their beneficial and harmful dual role becomes crucial.This thesis makes research on the antioxidant and prooxidant properties of -OH, -SH, -NH and C=C compounds systematically. Chemical system and chemical simulation biological system have been used in this research. The chemical systems include 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonate) radical cation(ABTS+) system, 2,2′-diphenyl-1-picrylhydrazyl(DPPH) system and galvinoxyl system. The chemical simulation biological systems include: AAPH-induced hemolysis system, AAPH-induced DNA oxidative system and hemin-induced hemolysis system etc. In this thesis, the kinetic equation was introduced into chemical simulation of biological systems, which can be used in biological system to evaluate the activity of antioxidants quantificationally. The research contents includes the following mainly:1. Studies on the antioxidants and prooxidants of -OH natural and synthetic compounds.We have tested the antioxidant properties of carminic acid, which contains several hydroxyl groups, found that carminic acid has good antioxidant properties in above mentioned systems. The inhibition concentration from 50% of free radicals(IC50) are 8.0μM and 26.0μM, when carminic acid reacted with ABTS+ and DPPH. Carminic acid can prevent AAPH-induced DNA oxidative damage and slow the formation rate of thiobarbituric acid down. Each carminic acid molecule can capture 3.12 free radicals in AAPH-induced hemolysis system. We have found that the hydroxyl group at 6-position in carminic acid molecule plays a major role through quantitative calculation, when carminic acid reacted with free radicals. We have synthesized a series of 4-hydroxyquinoline-3-carboxylic acid compounds, found that the antioxidant activities of them are not strong but presenting prooxidant properties. In order to further study, we studied on the L-ascorbyl-6-laurate(VC-12) which containing enolic group in the AAPH-induced hemolysis system, found that VC-12 possesses prooxidant activity. The antioxidant becomes prooxidant, when concentration of VC-12 is 60μM. We also have found that VC-12 itself can initiate hemolysis. We have used hemin-induced hemolysis system to study on the ginsenosides containing alcoholic hydroxyl group only. The total ginsenosides may delay the incidence of hemolysis and present activities stabilizing cell membrane. A varies of individual ginsenoside showed different characteristics, all the 20(S)-protopanaxatriol(PT) ginsenosides showed acitivities stabilizing cell membrane, the 20(S)-protopanaxadiol(PD) ginsenosides, except Rg3, Rh2 and PD, also showed activities stabilizing cell membrane, however, Rg3, Rh2, and PD showed prooxidant properties. We also found that Rg3 and Rh2 themselves can initiate hemolysis, when their concentration at 20μM.2. Studies on the antioxidants of–SH compoundsWe have tested the antioxidant activities of capropril(CAP), 6-mercaptopurine(6-MP) and 9-(?-D-ribofuranosyl)-6-mercaptopurine(6-MPR), found that CAP possesses highest activities scavenging free radicals in DPPH and galvinoxyl system, it demonstrated that CAP has a good activity providing H atom on the–SH. 6-MPR possesses a highest activity scavenging ABTS+, it demonstrated that 6-MPR has a highest reducing activity. CAP, 6-MP and 6-MPR can capture 1.33, 2.23 and 3.07 free radicals in AAPH-induced hemolysis system respectively, the sequence of capacities of capturing free radicals is: 6-MPR﹥-6MP﹥CAP. CAP, 6-MP and 6-MPR can capture 0.50, 0.61 and 0.97 free radicals in AAPH-induced DNA oxidation system respectively, the sequence of capturing free radicals is 6-MPR﹥-6MP﹥CAP. CAP shows activity stabilizing cell membrane only in hemin-induced hemolysis system.3. Studies on the prooxidants of–NH compoundsWe have tested the prooxidant properties of Phenothiazine(PtzNH) and phenoxazine(PozNH), found that they can initiate hemolysis themselves, when their concentration higher than 36μM. With the increasing of concentration of PozNH and PtzNH, the time of lagging incidence of hemolysis(tlag) was decreasing, when we have used AAPH as initiator, it demonstrated that high concentrations of PozNH and PtzNH can promote hemolysis. In addition, high concentration of AAPH can promote the prooxidant of PtzNH, however, PozNH presented prooxidant in the lower concentration of AAPH.4. Studies on the antioxidants and prooxidants of C=C compoundsWe have tested antioxidants and prooxidants of terpinenes, found that the antioxidant ofα-terpinene(α-TH) is higher thanγ-terpinene(γ-TH) in ABTS+ and DPPH system.α-TH andγ-TH can capture 0.39, 0.41 free radicals in AAPH-induced DNA oxidation system respectively, it demonstrated that the activity of capturing free racials ofγ-TH is slightly higher thanα-TH.α-TH andγ-TH can capture 0.71, 1.21 free radicals in AAPH-induced hemolysis system respectively, it demonstrated that the activity of capturing free racials ofγ-TH is higher thanα-TH. The activity of capturing free racials ofγ-TH is also higher thanα-TH in AAPH-induced methyl linoleate oxidation system. We also have found thatα-TH andγ-TH have prooxidant properties in hemolysis system, when we used high concentration of them.In summary, the -OH, -SH, -NH and C=C compounds possess prooxidant properties under certain conditions, the occurrence of prooxidant behavior is the result of using of the high concentration of antioxidants. We have not found that the -SH compounds possess prooxidant activity in the test system. We have found the prooxidant properties of antioxidants, it may lead people better utilize useful side of antioxidants and avoid harmful side.