Radical scavenging activity characterization of synthetic isochroman-derivatives of hydroxytyrosol: A gas-phase DFT approach

Abstract

Hydroxytyrosol (HT) and a set of synthetic isochroman derivatives of HT have been studied with regards to their radical scavenging activity in the gas employing density functional theory (DFT) and the Becke's 3 Lee Yang Parr (B3LYP) functional. Values of molecular descriptors (bond dissociation enthalpy, BDE; ionization potential, IP; proton dissociation enthalpy, PDE; proton affinity, PA; electron transfer energy, ETE; electron accepting power, ɷ+; electron donating power, ɷ-; net electrophilicity, Δɷ^±) characterizing the hydrogen atom or electron donating efficiency of test compounds were used. Published experimental findings for the radical scavenging activity of the same compounds using methods such as Rancimat, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical cation and oxygen radical absorbance capacity were discussed. All the synthetic isochromans were predicted to be more potent hydrogen atom and electron donors than HT, though polarity may affect their performance in lipidic systems. Present findings point out that HT and examined isochromans prefer to scavenge free radicals via hydrogen atom transfer instead of electron donation and that allylic hydrogen atoms are expected to account for a higher activity in comparison to other phenolic antioxidants. The most potent hydrogen atom donor was the one bearing two catechol groups which can form stepwise a di-quinone and then scavenge additional radicals via allylic hydrogen atom donation and subsequent adduct formation. The total enthalpy required for all hydrogen atoms donated by test compounds was the most appropriate index of experimental activity prediction instead of common descriptors.

Keywords: Bond dissociation enthalpy; DFT; Hydroxytyrosol; Isochroman; Structure–activity relationship.