Mehanizmi antioksidativnog delovanja bajkaleina

Abstract

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.

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: М05-2X, B3LYP and РВЕ, 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 В and С 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.