A DFT study of the reactivity of OH groups in quercetin and taxifolin antioxidants: The specificity of the 3-OH site

Over the past decade, the chemical behaviour of flavonoids as antioxidants has become the subject of intense experimental research. In this paper, we use a quantum-chemical approach to shed light on the reactivity of two flavonoids, quercetin and taxifolin. We particularly focus on the 3-OH site and the role played by the 2,3-double bond in the reactivity of that site. In order to establish the most efficient theoretical methodology, different methods, either Hartree–Fock-based or derived from density functional theory, and different basis sets (from 6-311G(d) to 6-311++G(2d,p)) were tested on phenol and catechol, for which experimental bond dissociation enthalpy (BDE) values are available. It appears that (U)B3P86/6-311+G(d,p) is the most relevant method for BDE prediction of these phenolic compounds and it has, therefore, been used for an extensive study of the two flavonoids.The analysis of the theoretical BDE values, for all OH sites of quercetin and taxifolin, clearly shows the importance of the B-ring and the 3-OH group only when the 2,3-double bond is present (i.e. in quercetin). We have also considered the importance of keto–enol tautomerism (present in quercetin but not in taxifolin) to rationalize the difference in reactivity between the two compounds. Our analysis also includes the Mulliken spin density distribution for the radicals formed after H-removal on each OH site of both flavonoids. The results clearly show that the 3-OH quercetin radical possesses a large spin density on the C-2 atom, which explains the C-ring opening process observed in different redox systems, including metabolization.