Investigation of the antioxidant properties of hyperjovinol A through its Cu(II) coordination ability

Hyperjovinol A (2-methyl-1-(2,4,6-trihydroxy-3-(3-hydroxy-3,7-dimethyloct-6-enyl)phen yl)propan-1-one) is an acylated phloroglucinol isolated from Hypericum Jovis and exhibiting antioxidant properties comparable with those of the most common antioxidant drugs. The study models the compound’s antioxidant ability through its ability to coordinate a Cu²⁺ ion and reduce it to Cu⁺. Complexes with a Cu²⁺ ion were calculated for all the low energy and for representative high energy conformers of hyperjovinol A, placing the ion in turn near each of the electron-rich binding sites. The most stable complexes are those in which Cu²⁺ binds simultaneously to the O of the OH in the geranyl-type chain (R′) and the C═C double bond at the end of R′, or to the O of a phenol OH and the O of the OH in R′. The most stable complexes in which Cu²⁺ binds only to one site are those in which it binds to the C═C double bond at the end of R′ or to the sp² O of the COCH(CH₃)₂ acyl group. Cu²⁺ is reduced to Cu⁺ in all complexes. Comparisons with corresponding complexes of other molecular structures in which one or more of the structural features of hyperjovinol A are modified attempt to elucidate the role, for the antioxidant ability, of relevant features of hyperjovinol A, like the presence and position of the OH or the C═C double bond in R′. Calculations at the DFT/B3LYP/6–31+G(d,p) level were performed for all the structures considered. Calculations utilizing the LANL2DZ pseudopotential for the Cu²⁺ ion were also performed for hyperjovinol A.