Multitask Quantum Study of the Curcumin‐Based Complex Physicochemical and Biological Properties

Density functional theory (DFT), time‐dependent density functional theory (TDDFT), quantum theory of atoms in molecules (QTAIM), and extended transition state natural orbitals for chemical valence (ETS‐NOCV) have all been used to investigate the physicochemical and biological properties of curcumin and three complexes, i.e., Cur‐M (M = Ni, Cu, and Mg). Based on DFT calculations, the enolic form (Cur‐Enol) is more stable than the anti‐diketone form (Cur‐Anti diketone) favored for complexation. This enolic form stability was explained by the presence of three intramolecular hydrogen bonds according to the QTAIM analysis. Furthermore, the ETS‐NOCV technique revealed that the enolic form had more significant antioxidant activity compared with the anti‐diketone form. The calculations from the COnductor‐like Screening MOdel for Realistic Solvents (COSMO‐RS) showed that the dimethyl sulfoxide (DMSO) solvent could dissolve all the curcumin tautomers Cur‐Enol, Cur‐Anti‐diketone and Cur‐Cu, Cur‐Mg, and Cur‐Ni complexes in contrast to benzene, acetone, octanol, ethanol, methanol, and water. Furthermore, except for Cur‐Mg, which had a relatively low solubility (14 g/L), all complexes were insoluble in water. Cur‐Antidiketone was considerably more soluble than Cur‐Enol in the examined solvents.