Hydroxyl Radical Scavenging by Aucubin: A Mechanistic Study.

Area of Science:

• Computational Chemistry
• Biochemistry
• Pharmacology

Background:

• Aucubin (AU) is an iridoid compound with potential antioxidant properties.
• Hydroxyl radicals (•OH) are highly reactive species implicated in oxidative stress.
• Understanding the radical scavenging mechanisms of natural compounds is crucial for therapeutic development.

Purpose of the Study:

• To investigate the antioxidant properties of aucubin (AU).
• To elucidate the primary mechanisms by which AU scavenges hydroxyl radicals (•OH).
• To identify the key active sites within the AU molecule responsible for radical scavenging.

Main Methods:

• Density Functional Theory (DFT) calculations using the M06-2X functional and def2-TZVP basis set.
• Modeling of antioxidant reaction mechanisms: Hydrogen Atom Transfer (HAT), Sequential Electron Transfer-Proton Transfer (SET-PT), and Sequential Proton Loss-Electron Transfer (SPLET).
• Calculation of thermodynamic parameters including Bond Dissociation Energy (BDE), Ionization Potential (IP), Proton Dissociation Enthalpy (PDE), Electron Transfer Enthalpy (ETE), and Proton Affinity (PA).
• Inclusion of Grimme's D3 dispersion correction and the SMD solvation model for water.

Main Results:

• The Hydrogen Atom Transfer (HAT) mechanism was identified as the dominant pathway for •OH radical scavenging by AU.
• The 6-OH group on the aglycone and the 6'-OH group on the sugar moiety were identified as the primary active sites.
• Thermodynamic parameters supported the HAT mechanism's prevalence.
• A polar aqueous environment was found to enhance AU's antioxidant activity by promoting O-H bond homolysis.

Conclusions:

• Aucubin (AU) exhibits significant antioxidant activity against hydroxyl radicals (•OH) primarily via the HAT mechanism.
• The specific hydroxyl groups on both the aglycone and sugar parts of AU are critical for its radical scavenging ability.
• The solvent environment plays a role in modulating the antioxidant efficacy of AU, with aqueous conditions being favorable.