Unravelling the effect of β-diketo group modification on the antioxidant mechanism of curcumin derivatives: A combined experimental and DFT approach

Abstract Curcumin (CU), a natural polyphenol exhibits free radical scavenging activity by three main mechanisms namely, HAT (hydrogen atom transfer), SPLET (sequential proton loss electron transfer) and SET-PT (sequential electron transfer-proton-transfer). In this study, the influence of structural modification of curcumin to its isoxazole (CI) and pyrazole (CP) on their free radical scavenging mechanism has been investigated. For this, CI and CP were first screened for their free radical scavenging ability using different free radicals like DPPH• (1,1-diphenyl-2-picrylhydrazyl), ABTS•– (2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)), O2•– (superoxide), N3• (azide), CCl3O2• (trichloromethyl peroxyl), lipid peroxyl (LOO•) radicals, FRAP (Ferric reducing antioxidant power) assay and the results were compared with CU. The reaction mechanism was explained by complementing the experimental results with molecular descriptors obtained from quantum chemical calculations. The dependence of the scavenging activity on the acidity of the solvent indicated that CU and its derivatives reacted with DPPH•, ABTS•–, O2•–, LOO• radicals and ferric ion by SPLET mechanism, while they reacted with N3• and CCl3O2• radical by SET-PT mechanism. In case of free radicals neutralized by SPLET mechanism, the IC50 value of the polyphenols (the concentration of the polyphenol required to scavenge 50% radical) increased in the order CU   CI > CU. Using DFT calculations, the pKa of the parent molecule and their corresponding one-electron oxidized radicals were calculated. In the case of parent molecule the pKa increased in the order CU