Reactivity of Curcumin: Theoretical Insight from a Systematic Density Functional Theory-Based Review

A comprehensive analysis of key findings derived from density functional theory (DFT) studies reveals that current theoretical data on curcumin remain incomplete, underscoring the need for further computational investigation to achieve a more thorough understanding of its chemical and biological reactivity. This study addresses these gaps through four primary objectives: (i) determination of a complete set of thermodynamic descriptors and elucidation of the multi-step anti-radical mechanisms of the neutral, radical, anionic, and radical–anionic forms of curcumin; (ii) calculation of global chemical reactivity descriptors of curcumin in various solvent environments; (iii) theoretical reproduction of experimentally determined pKa values for all active sites within the molecule; and (iv) examination of the effects of dispersion interactions and solvent polarity on the reactivity descriptors of keto–enol forms of curcumin. The results obtained provide enhanced insight into the molecular behavior of curcumin, facilitating improved predictions of its reactivity under diverse conditions. Moreover, the findings indicate a potential structural modification of the keto form of curcumin, involving the attachment of two 4-hydroxy-3-methoxyphenyl-prop-1-en-2-one moieties to the methylene group. The resulting modeled compound, referred to as di-curcumin, exhibits enhanced chemical reactivity and increased anti-radical potential.