Investigation of the influence of Z/E configuration on the antioxidant and antiradical activities of lapachol and its derivatives: DFT assessment

The geometry optimization of a series of twenty-seven lapachol derivatives used for the treatment of carcinosarcoma tumor (Walker 256) is performed at B3LYP/6–311++G(d,p) level in three distinct media (gas phase, water, and acetonitrile). The migration from the E to the Z configuration or vice versa provokes a noticeable change in the O–H bond distance and potentially a remarkable alteration of the antioxidant activity. In addition, the majority of the E configuration structures have shown a more pronounced antioxidant activity in solution (water and acetonitrile). In their various Z/E configurations, the 2-hydroxy-3-(2,3-dihydroxy-3-methylbutyl)-1,4-naphtoquinone compound bearing O···HO hydrogen bond ( La21(HB) ) as well as the (2-hydroxy-3-(but-2-enyl)-1,4-naphtoquinone ( La6(HB) ) and 2-hydroxy-3-(3-methylpent-2-enyl)-1,4-naphtoquinone ( La7(HB) ) compounds have stronger antioxidant powers than classical bioactive compounds (caffeic acid, ferulic acid, p-coumaric acid, sinapic acid, and vitamin C). On the whole, however, all Z configuration compounds have a higher antiradical status compared to that of their E configuration counterparts. From the global donor–acceptor mappings, the 2-hydroxy-3-(2,3-dihydroxy-3-methylbutyl)-1,4-naphtoquinone structure ( La21 (HB)) has been elected as the best antiradical molecule of the series in the three study media. Its antiradical power has been detected to be higher than that of these five standard references adopted.