Enhanced Antioxidant Properties of Novel Curcumin Derivatives: A Comprehensive DFT Computational Study

Abstract Oxidative stress, driven by the accumulation of free radicals and reactive oxygen species (ROS) in the human body, is a key contributor to various diseases. Curcumin, a polyphenolic compound derived from turmeric, has garnered attention for its antioxidant potential. In this context, a recent experimental study by Hao et al. introduced curcumin derivatives with incorporated electron-donating groups (allyl and isopentenyl), aiming to enhance antioxidant activity while circumventing the limitations of traditional curcumin. Building upon this experimental foundation, our study employs computational techniques (DFT) to unravel the molecular mechanisms underpinning the superior antioxidant effects observed in these novel derivatives. We investigated three prominent antioxidant mechanisms: Hydrogen Atom Transfer (HAT), Single Electron Transfer-Proton Transfer (SET-PT), and Sequential Proton Loss Electron Transfer (SPLET). Our results reveal that the allyl and isopentenyl groups play pivotal roles in enhancing the antioxidant properties of the derivatives, as evidenced by reduced bond dissociation energies (BDEs) and favorable proton dissociation energies (PDEs). Moreover, the analysis of Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) energies indicates their enhanced reactivity as electron donors and acceptors. Notably, the computational investigation of spin densities validates the radical scavenging potential of these derivatives. While curcumin exhibits limitations such as low water solubility, bioavailability, and stability, our findings suggest that the strategically designed derivatives (especially exhibit superior antioxidant properties, positioning them as promising candidates for further therapeutic applications. This comprehensive study bridges experimental findings with computational insights to unravel the intricate molecular mechanisms driving the enhanced antioxidant efficacy of the newly developed curcumin derivatives.