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Curcumin, a yellow pigment extracted from the rhizome of Curcuma longa, commonly known as turmeric, is the most active agent of this herbal medicine. The therapeutic activities of curcumin are exemplified not only by its enhancement in wound healing but also in the treatment of inflammation, cystic fibrosis, Alzheimer's disease and cancer. There are two critical issues involving low aqueous stability and solubility that limit the bioavailability and application of curcumin as a therapeutic agent. To address these issues, delivery systems of curcumin including surfactant micelles, liposomes, polymer nanoparticles, casein micelles, plasma proteins and cyclodextrins have been developed and characterized. From a biochemical perspective, the medicinal activities of curcumin are proposed to be related to an elevated level of transition metals including copper, zinc and iron in many disease sites, especially those in cancer and Alzheimer's disease. Previous studies have demonstrated the importance of copper(II)-curcumin complexes in DNA damage owing to the strong interaction between curcumin and copper(II). Curcumin, as an anti-oxidant, possesses the abilities to scavenge radicals and maintain the levels of anti-oxidant enzymes in the presence of copper. On the other hand, copper(II)-curcumin complexes show pro-oxidant effects by generating reactive oxygen species at a high free copper level in a reducing environment. This condition results in DNA damage and inhibition of vital signaling pathways in cancer cells, leading to apoptosis. In short, curcumin has dual roles as an anti-oxidant and a prooxidant in the presence of copper and these fascinating phenomena contribute greatly to its multiple medicinal effects.

Density functional theory is used to obtain the lowest energy geometries of bis-aqua curcumin complexes and bis-curcumin complexes of Cu(I) and Cu(II). Three conformations of curcumin, obtained by rotation of the substituted aromatic groups, were considered in each case. Steric repulsion, due to the methoxy–methoxy interactions, was found to be an important factor in determining the lowest energy conformer of Cu(II)(curcumin)2 but was less important for the Cu(I) analog. Using a sufficiently large basis set, the results show that the lowest energy Cu(II)(curcumin)2 geometry is square planar around the copper atom, in contrast to the results from a previous study (Shen et al. THEOCHEM-J Mol Struct 2005, 757, 199). In addition, other studies suggested that the formation of this complex is followed by the reduction of Cu(II) to Cu(I). We also examined the singly occupied molecular orbital, spin density, and natural bond orbitals of Cu(II)(curcumin)2. While the former two analyses show little evidence of electron transfer from curcumin into the Cu center, the latter indicates that Cu(II) is partially reduced to Cu(I) as a consequence of complexation. Finally, we consider the bis-aqua curcumin and bis-curcumin complexes on a reaction path involving progressive displacement of water molecules by curcumin ligands. The results show that the bis-curcumin complex is the most stable Cu(II) complex, showing consistently exothermic steps in the reaction path. However, for Cu(I), the final step in the reaction path is essentially thermoneutral, indicating that the 1:1 and 1:2 Cu(I) complexes are equally stable thermodynamically.