Novel imidazo[4,5-b]pyridine derived acrylonitriles: A combined experimental and computational study of their antioxidative potential

Abstract We describe the synthesis of novel unsubstituted and N-substituted imidazo[4,5-b]pyridine derived acrylonitriles, which were prepared by classical and microwave assisted organic synthesis. Their antioxidative potential was studied using spectroscopic DPPH and ABTS assays, FRAP method and electrochemical oxidation potential measurements. Targeted acrylonitriles were designed in order to study the influence of the methoxy, N,N-dimethylamino and N,N-diethylamino substituents on the antioxidative activity as well as the type of the substituent placed on the N-atom of the imidazo[4,5-b]pyridine nuclei. The most active derivatives with significantly improved activity relative to the standard BHT, were systems substituted with the N,N-(CH3)2 group 29 and the N,N-(CH2CH3)2 group at the para position of the phenyl ring 24, 30, 32 and 34. Computational analysis revealed that investigated antioxidative features are predominantly relying on the hydrogen atom transfer properties and can be efficiently enhanced through either the N-alkylation of the imidazole nitrogen or by introducing electron-donating substituents on the distant phenyl unit, where N,N-dialkylamines prevail over methoxy groups. Absorption spectra of chosen compounds were recorded in several organic solvents to further reveal the impact of the substituent effects and solvent polarity on spectroscopic features.