Complexes of arzanol with a Cu 2+ ion: a DFT study.

Arzanol (C22 H26 O7 ) is a naturally occurring acylphloroglucinol largely responsible for the anti-inflammatory, anti-oxidant, antibiotic and antiviral activities of Helichrysum italicum. Like all acylphloroglucinols, the molecule contains a carboxylic substituent (-COR group); for arzanol, this is a -COCH3  group. The molecule is further characterized by the presence of an α-pyrone ring bonded in meta to -COR through a methylene bridge, and of a prenyl chain bonded to the other meta position. The molecule can form up to three intramolecular hydrogen bonds (IHB) simultaneously, and their presence and patterns are the major stabilizing factors. This work considers complexes of representative conformers of arzanol with a Cu2+ ion, taking into account the different possibilities for the binding of the Cu2+ ion to the electron-density rich sites of the molecule and including simultaneous coordination to two geometrically suitable sites. Calculations were performed at the DFT/B3LYP level, using the 6-31+G(d,p) basis set for the C, O and H atoms and the LANL2DZ pseudopotential for the Cu2+ ion. Interaction energies show preference for simultaneous binding of Cu2+ to two sites. Simultaneous binding to the O of a phenol OH neighboring the prenyl chain and to the π bond of the prenyl chain appears to be the most favorable option, followed by simultaneous binding to the sp2 O of the α-pyrone ring and the O of the phenol OH ortho to -COR on the side of the α-pyrone ring. The charge of the Cu2+ ion is reduced to +1 or slightly less in the complexes, which is consistent with the molecules' antioxidant (reducing) ability. Graphical abstract The copper ion prefers to attach to two sites of the arzanol molecule simultaneously. The arzanol molecule reduces the charge of the copper ion from +2 to +1 by transferring an electron to it; it becomes a radical molecular cation. The distribution of the unpaired electron in the molecule (as highlighted by the spin density maps) depends on the site/s to which the Cu2+ ion binds and on the molecule's conformer.