Structure–activity relationships of new 4-hydroxy bis-coumarins as radical scavengers and chain-breaking antioxidants

The main antioxidant properties of five new 4-hydroxy-bis-coumarins during bulk lipid autoxidation at 80 °C and 0.1 mM and 1.0 mM concentrations were studied and compared with 4-hydroxy-2H-chromen-2-one ( 1). These compounds are: 3,3′-((3,4-dihydroxy-phenyl) methylene) bis (4-hydroxy-2H-chromen-2-one) ( 2), 3,3′-((3,4-dimethoxyphenyl) methylene) bis (4-hydroxy-2H-chromen-2-one) ( 3), 3,3′-((4-hydroxy-3,5-dimethoxy-phenyl) methylene) bis(4-hydroxy-2H-chromen-2-one) ( 4) 3,3′-((3,4,5- trimethoxyphenyl) methylene) bis (4-hydroxy-2H-chromen-2-one) ( 5) 3,3′-((4-hydroxy-3-methoxy-5-nitrophenyl) methylene) bis (4-hydroxy-2H-chromen-2-one) ( 6), It was found that compound 2 with a catecholic structure in the aromatic nucleus showed the strongest antioxidant activity. Compound 4 showed a moderate antioxidant activity, and all the other compounds didn't show any capacity as chain-breaking antioxidants. Both 4-hydroxy-bis-coumarins ( 2 and 4) demonstrated also stronger radical scavenging activity towards DPPH radical by using TLC DPPH rapid test, than compound 1. The other compounds ( 3, 5, 6) didn't show any capacity as radical scavengers. The structure–activity relationship was discussed on the base of comparable kinetic analysis of studied 4-hydroxy-bis-coumarins with the known and standard antioxidants as α-tocopherol (TOH), caffeic acid (CA), sinapic acid (SA), ferulic acid (FA), and p-coumaric acid (p-CumA). In order to study the possible synergism between two phenolic antioxidants, the antioxidant efficiency and reactivity of two equimolar binary mixtures of coumarins and TOH ( 2 + TOH and 4 + TOH) and of corresponding cinnamic acid with TOH (CA + TOH and SA + TOH) were also tested and compared. The oxidation stability of the lipid substrate in presence of binary mixtures CA + TOH, SA + TOH and 2 + TOH appeared to be higher than that of the individual antioxidants. However, no synergism was obtained for all tested binary mixtures.