A DFT Study Of Structure-Antioxidant Activity Relationship of a New Series of 2-Methoxybezohydrazide Schiff Bases

ABSTRACT

Natural and synthetic Schiff bases are known for their diverse biological activies and potent antioxidant and free radical scavenging activity. A series of 31 Schiff bases (e.g. 2) were synthetized through the condensation of 2- methoxybenzohydrazide (1) and different aldehydes in methanol. The antioxidant activities of these Schiff bases were evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test. To rationalize their structure-antioxidant activity relationship, density functional theory (DFT) calculations have been performed at B3P86/6-31+G(d,p) level in gas phase and in solvent using a polarizable continum model (PCM). Both experimental and DFT results emphasize the importance of the (i) catechol moiety, (ii) number of OH groups, (iii) delocalization of spin density (such as in 3), and (iv) bond dissociation enthalpies (BDE for a first hydrogen atom transfer and BDEd for a second hydrogen atom transfer) in the antioxidant activity of that series of Schiff bases. Thermodynamic and kinetic studies of the reactivty of Schiff bases with free radicals (e.g. DPPH and ●OOCH₃) have shown that the coupled proton electron transfer (CP-ET) is the major mechansim to scavenge free radicals due to low free activation barriers as compared to the electron transfer proton transfer (ET-PT) mechanism.

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