Study On The Capacities Of Compounds Containing Ferrocenyl And [2Fe2Se] Cluster

The investigation of antioxidant is not only an important content in medicine, butalso a focus in chemistry, especially in physical organic chemistry.Recently, the investigations of antioxidant focus on the modification of naturalantioxidants. However, most strategies are limited in traditional organic molecules.Nowadays, introducing ferrocenyl and other organometallic groups is a new strategywidely used in drug design and modification. Wether the same strategy can be used toget antioxidants with high activities and how their structure-activity relationshipsexhibit are less reported.Therefore, in this work, the strategy of introducing ferrocenyl group is employedto improve antioxidants. Ferrocenyl curcumin derivatives, ferrocenyl dihydropyrazoleand pyrazole “core-shell”(dendritic like) derivatives and ferrocenyl mono-carbonylcurcumin and their dihydropyrazole derivatives were synthesized. Besides, butterfly[2Fe2Se] cluster complexes contaning [2Fe2Se] cluster instead of ferrocenyl groupwere also synthesized and the antioxidant abilities of these compounds to scavengeradicals and protect DNA against oxidation were evaluated. Moreover, the [2Fe2Se]cluster complex was also tested in micelle systems to investigate its activity inmicroenvironment. The major work in this thesis is carried out as the followingaspects: 1. Synthesis and evaluation of ferrocenyl curcumin derivativesIn this part, three ferrocenyl curcumin derivatives were synthesized and theirantioxidant abilities to scavenge DPPH, ABTS, Galvinoxyl radicals and to protectDNA against AAPH-, Cu2+/GSH-, HO-induced oxidation were evaluated.In scavenging DPPH and ABTS radicals, compound with two phenolic hydroxylgroups possesses the highest ability, while for the other two, the mono-carbonylcompound is somewhat better than the di-carbonyl one. However, all of the threecompounds are non-effective in scavenging Galvinoxyl radical. It is the same resultthat the compound with two phenolic hydroxyl groups is also the best in protectingDNA against AAPH-induced oxidation, while the activities of the other two aresimilar. In protecting DNA against Cu2+/GSH-induced oxidation, compound withmono-carbonyl possesses the highest ability. For the other two, the one with twophenolic hydroxyl groups is better. Nevertheless, all the compounds exhibitprooxidant effect in HO-induced oxidation of DNA. From the results aforementioned,the antioxidant abilities of ferrocenyl curcumin derivatives are very well, only exceptno effect in scavenging Galvinoxyl radical and prooxidant effect in HO-inducedoxidation of DNA.2. Synthesis, antioxidant abilities and structure-activity relationship of ferrocenyldihydropyrazole and pyrazole “core-shell” derivativesIn this part, eight ferrocenyl dihydropyrazole and pyrazole “core-shell”derivatives were synthesized. In order to investigate the effect of ferrocenyl and thestructure-activity relationship in detail, three corresponding non-ferrocenyl derivativeswere also synthesized. Their antioxidant abilities to scavenge ABTS radical andprotect DNA against AAPH-induced oxidation incorporating structure-activityrelationship were all investigated quantitatively.Phenyl replaced by ferrocenyl improves antioxidant abilities of most compounds,both in scavenging ABTS radical and protecting DNA. Dihydro-structure indihydropyrazole core is also effective, like phenolic hydroxyl. For hydroxyl, compounds will get optimal activity to protect DNA when it places on the B-ring.Nevertheless, the dihydropyrazole derivatives will get optimal activity to scavengeABTS radical when it places on the A-ring, while it is on the B-ring for the pyrazolederivatives. However, the effect of ferrocenyl, hydroxyl and dihydro-structure is notindependent. In scavenging ABTS radical, the relationship between any two factors issynergetic but it is antagonistic when all of the three factors exist together. Inprotecting DNA, the relationship between any two factors is synergetic only exceptfor the situation between hydroxyl group and dihydro-structure. But if all of the threefactors exist together, it will give out a highly synergetic result, which is quitedifferent from that in scavenging ABTS radical.3. Synthesis and evaluation of ferrocenyl mono-carbonyl curcumin and theirdihydropyrazole derivatives.From the conclusions in part1and part2, fifteen ferrocenyl and non-ferrocenylmono-carbonyl curcumin and their dihydropyrazole derivatives were synthesized inthis part, and their antioxidant abilities to scavenge ABTS radical and protect DNAwere evaluated.The results of phenyl replaced by ferrocenyl are also positive and the ferrocenylvinyl structure is necessary to inhibit the oxidation of DNA completely, both inmono-carbonyl and dihydropyrazole structures. In mono-carbonyl structure, theantioxidant ability to protect DNA is optimal when the substituent is p-dimethylamino,while it is p-hydroxyl in scavenging ABTS radical. However, in dihydropyrazolestructure, the antioxidant ability to protect DNA is optimal when the substituent ism-ethyoxyl-p-hydroxyl, while it is p-dimethylamino in scavenging ABTS radical.Ferrocenyl, dihydro-structure and groups on benzene are also related.4. Synthesis and evaluation of butterfly [2Fe2Se] cluster complexesIn this part, a butterfly [2Fe2Se] cluster complex with aliphatic hydroxyl and itsacetyl derivative were synthesized. Their antioxidant abilities to protect DNA againstAAPH-, Cu2+/GSH-and HO-induced oxidation were evaluated. Furthermore, the activity of the former to inhibit oxidation of DNA induced by AAPH inmicroenvironment was also tested in micelles.From the results, in AAPH-induced oxidation of DNA, the active group isaliphatic hydroxyl which connects to the [2Fe2Se] cluster.[2Fe2Se] cluster isnecessary for aliphatic hydroxyl to possess the activity, but it is not active itself. Bothof the two compounds have no effect in Cu2+/GSH-induced oxidation of DNA, butexhibit prooxidant effect in HO-induced oxidation of DNA as FeIin the [2Fe2Se]cluster participates in Fenton reaction. Moreover, the one with aliphatic hydroxyl alsoshows activity to protect DNA against AAPH-induced oxidation to some degree inmicelles, but the activity is related to the kind and concentration of micelle.In conclusion, the strategy of introduing ferrocenyl group and [2Fe2Se] cluster toimprove the antioxidants is effective. But the prooxidant effect of theseorganometallic groups in some conditions should also draw attention.