A Theoretical Study On The Reaction Mechanisms Of Four Licorice Flavonoids Scavenging Free Radicals In Vivo

Organism has the free radical scavenging system,because the excessive generation of free radicals or the failure of the antioxidant system in the body causes the excessive accumulation of free radicals,it will cause disease and accelerate aging.Therefore,searching natural and highly efficient free radical scavengers has become a hot topic in current research.Licorice flavonoids are a kind of natural antioxidants widely found in licorice with significant antioxidant activity.Therefore,the study of the mechanism of licorice flavonoids scavenging free radicals in vivo is of great significance to the search of the natural antioxidants in licorice.In this paper,the density functional theory was used to study the microscopic reaction mechanism of the four kinds of licorice flavonoids,liquiritigen,isoliquiritigenin,uralenol and neouralenol,respectively scavenging three reactive oxygen species ·OH,·OOH and ·OOCl3C in vivo.At the level of M06-2X/6-311+G(d,p),the geometries of all stationary points for Hydrogen Atom Transfer(HAT)and Radical Adduct Formation(RAF)pathways were optimized.The thermodynamic parameters and kinetic parameters of each reaction channel were obtained,and the potential energy surface information of each reaction channel was obtained too.The calculation results show that when liquiritigen and isoliquiritigenin trap active oxygen radicals of ·OH and ·OOCl3C in vivo,the Gibbs free energy of each active site is less than zero,and the reaction can proceed spontaneously,while during the capture of ·OOH–active oxygen free radicals in the body,the reaction should not proceed spontaneously.When uralenol and neouralenol capture the three kinds of active oxygen radicals including ·OH,·OOH,and ·OOCl3C,except for the reaction when the ·OOH reactive oxygen radical is captured by the C3 channel on the C ring of uralenol,the rest of the channels can be performed spontaneously.Using the continuum solvation model based on solute electron density(SMD),the influence of the solvation effect on the reaction was calculated in this paper.The main mechanisms and reactive sites for the capture of three active oxygen free radicals by four licorice flavonoids,liquiritigen,isoliquiritigenin,uralenol and neouralenol,were determined.Research indicates: Liquiritigen captures three kinds of active oxygen radicals such as ·OH,·OOH and ·OOCl3C by hydrogen abstraction reaction.The hydroxyl reaction channel on the liquiritigen B' ring is the main reactive site.Isoliquiritigenin captures three free radicals in the body through addition reaction and hydrogen abstraction.The addition reaction channel is the dominant reaction channel.The C1 site on the carbon-carbon double bond linking the two benzene rings is the main reactive site.In the capture of three active oxygen free radicals in vivo,the reactivity of C1 on isoliquiritigenin was better than that of B'4 on liquiritigenin.Both uralenol and neouralenol capture the three active oxygen free radicals of ·OH,·OOH and ·OOCl3C in the body through hydrogen abstraction mechanisms.When uralenol captures three free radicals in vivo,the main reactive sites are at sites C3,A4,and B6,respectively.When neouralenol traps three free radicals in vivo,the main reactive sites are located at C'4,C'3 and B'2 sites,respectively.By this study,the microscopic reaction mechanism of free radicals captured by liquiritigen,isoliquiritigenin,uralenol,and neouralenol,four kinds of licorice flavonoids,was clarified.And the potential energy surface information that was difficult to determine experimentally was also obtained.It provides a reliable theoretical basis for the further screening of high active natural free radical scavengers of flavonoids in licorice,and provides the support for the improvement of the development and application technology of licorice.