Provider: - Institution: - Data provided by Europeana Collections- Antioxidative activity of flavonoids has been a subject of intensive experimental and theoretical investigation. Nevertheless, the research concerning antioxidative action of baicalein has been initiated only recently. Within this doctoral disertation the mechanisms of antioxidative action of baicalein: HAT (Hydrogen Atom Transfer), SET-PT (Sequential Electron Transfer – Proton Transfer), and SPLET (Sequential Proton Loss Electron Transfer) were examined. The investigation of antioxidative activity of baicalein was performed in correlation with the investigation of structural and electronic properties of baicalein. The results of the present doctoral disertation were obtained by using the DFT methods, as implemented in the Gaussian program package: M05-2X, B3LYP and RVE, combined with the 6-311+G(d,p) and 6-311+G(2df,p) basis sets. The calculations were performed for the gas phase and aqueous solution. To estimate the effects of water as solvent a continuum-based solvation model, CPCM, was used. The NBO (Natural Bond Orbital) analysis of all optimized geometries was performed, to reveal the effects that emanate from the electronic structure. Baicalein is a non-planar molecule, as documented with the experimental (9.0°) and calculated (24.5º) value for the dihedral angle between the V and S rings. In its most stable conformation baicalein has three hydrogen bonds with the stabilizing effect. The DH(H5--O4) hydrogen bond contributes most to the stabilization of the baicalein molecule. This finding was confirmed with the NBO analysis. The vibrational and UV/Vis spectra of baicalein were simulated, and compared to the corresponding experimental spectra. Excellent agreement between the experimentally obtained and simulated IR, Raman and UV spectra was achieved. Using the simulated spectra, a precise assignation of the vibrational modes in the IR and Raman spectra was accomplished. Some molecular orbitals of baicalein were distinguished. The electron transitions responsible for the UV spectrum occur among these orbitals. All radicals, anions, and radical cation of baicalein were examined, because they play a significant role in the antioxidative mechanisms of baicalein. The 6 site is most favorable for homolytic cleavage of the О–Н bond in the gas phase, whereas the 7 site is most favorable for heterolytic cleavage of the О–Н bond in the aqueous solution. The spin density distribution in the most stable О6R1 radical reveals that the unpaired electron is delocalized very well. This finding can explain the stability of this radical and antioxidative action of baicalein according to the НАТ mechanism. The charge distribution in the most stable anion О7А2 showed that there is delocalization of the negative charge in the А ring. This anion is strongly stabilized in the aqueous solution. Antioxidative action of baicalein according to the SPLET mechanism can be attributed to this fact. Our investigations predict a planar structure of the baicalein radical cation. An interesting feature of the radical cation in comparison to the baicalein molecule is that the H atom is transferred from О5 to О4. In this way delocalization of the unpaired electron is realized over the A ring, and, thus, the instability induced by the loss of an electron is reduced. Heterolytic dissociation of the radical cation yields three radicals. The structures of all three radicals were examined. It was found that the spin density delocalization is most pronounced in the thermodynamically most stable C6–O radical. BDE, PА, and IP values served to determine thermodynamically most favorable reaction pathway. The НАТ mechanism is most favorable reaction pathway for antioxidative action of baicalein in the gas phase. On the other hand, the SPLET mechanism is most favorable reaction pathway for antioxidative action of baicalein in the aqueous phase. SETPT is not favorable mechanism of antioxidative action of baicalein in either gas or aqueous phase. Mechanistic investigations of antioxidative action of baicalein have been commenced. A simulation of the reaction of baicalein with the hydroxyl radical confirmed that HAT is the dominant reaction pathway in the gas phase, and that the 6 position is most reactive. Due to the higher energies of the p orbitals of the hydroxide and methanthiolate anions in comparison to the energy of the SOMO of the radical cation, the radical cation does not conform to the SET-PT, but to the HAT mechanism in the gas phase. So far, our mechanistic investigations are in perfect accord with the results of theromodynamical research. Bearing in mind the findings of previous research regarding antioxidative activity of flavonoids, the results of this doctoral disertation provide a significant contribution to understanding the complex mechanisms through which antioxidative action of baicalein is realized. It should be emphasized that there are very few published results in this scientific field. It is expected that these results, by applying complementary approaches, will contribute to a better understanding of the structural and electronic properties of other polyphenols.- Iako je antioksidativna aktivnost flavonoida objekat veoma intezivnog eksperimentalnog i teorijskog istraživanja, antioksidativno delovanje bajkaleina se ispituje tek odnedavno. U okviru ove disertacije ispitivani su mehanizmi antioksidativnog delovanja bajkaleina, i to HAT (Hydrogen Atom Transfer), SET-PT (Sequential Electron Transfer – Proton Transfer) i SPLET (Sequential Proton Loss Electron Transfer). Ispitivanje antioksidativnih aktivnosti bajkaleina je izvedeno u korelaciji sa ispitivanjem strukturnih i elektronskih osobina bajkaleina. Rezultati ove doktorske disertacije dobijeni su pomoću metoda funkcionala gustine, koje su implementirane u programski paket Gaussian: M05-2X, B3LYP i RVE, u kombinaciji sa bazisnim skupovima 6-311+G(d,p) i 6-311+G(2df,p). Proračuni su izvedeni za gasovitu fazu i vodeni rastvor. Za procenu efekata vode kao rastvarača korišćen je solvatacioni model zasnovan na kontinumu – SRSM. Urađena je NBO (Natural Bond Orbital) analiza svih optimizovanih geometrija radi utvrđivanja efekata koji proističu iz elektronske strukture. Bajkalein je neplanaran molekul, što pokazuje eksperimentalna (9.0°) i izračunata (24.5º) vrednost za diedarski ugao između prstenova V i S. U najstabilnijoj konformaciji bajkalein ima tri vodonične veze koje imaju stabilizacioni efekat. Vodonična veza DH(H5--O4) daje najveći doprinos stabilizaciji molekula bajkaleina, što je potvrdila i NBO analiza. Izvršeno je simuliranje vibracionih i UV/Vis spektara bajkaleina i poređenje sa odgovarajućim eksperimentalnim spektrima. Postignuto je odlično slaganje između eksperimentalno dobijenih i simuliranih IR, Ramanskih i UV spektara. Uz pomoć simuliranih spektara izvršena je precizna asignacija vibracionih modova u IR i Ramanskom spektru. Određene su molekulske orbitale bajkaleina između kojih se vrše elektronski prelazi odgovorni za UV spektar. Ispitani su svi radikali, anjoni i radikal katjon bajkaleina, koji imaju važnu ulogu u antioksidativnim mehanizmima bajkaleina. Položaj 6 najpovoljniji je za homolitičko raskidanje O–N veze u gasovitoj fazi, dok je položaj 7 najpovoljniji za heterolitičko raskidanje O–N veze u vodenoj fazi. Raspodela spinske gustine u najstabilnijem O6R1 radikalu pokazuje da je nespareni elektron veoma dobro Izvršeno je simuliranje vibracionih i UV/Vis spektara bajkaleina i poređenje sa odgovarajućim eksperimentalnim spektrima. Postignuto je odlično slaganje između eksperimentalno dobijenih i simuliranih IR, Ramanskih i UV spektara. Uz pomoć simuliranih spektara izvršena je precizna asignacija vibracionih modova u IR i Ramanskom spektru. Određene su molekulske orbitale bajkaleina između kojih se vrše elektronski prelazi odgovorni za UV spektar. Ispitani su svi radikali, anjoni i radikal katjon bajkaleina, koji imaju važnu ulogu u antioksidativnim mehanizmima bajkaleina. Položaj 6 najpovoljniji je za homolitičko raskidanje O–N veze u gasovitoj fazi, dok je položaj 7 najpovoljniji za heterolitičko raskidanje O–N veze u vodenoj fazi. Raspodela spinske gustine u najstabilnijem O6R1 radikalu pokazuje da je nespareni elektron veoma dobro.- All metadata published by Europeana are available free of restriction under the Creative Commons CC0 1.0 Universal Public Domain Dedication. However, Europeana requests that you actively acknowledge and give attribution to all metadata sources including Europeana