Relationship between hydrophobicity and antioxidant ability of "phenolipids" in emulsion: a parabolic effect of the chain length of rosmarinate esters.

The polar paradox predicts that hydrophobic antioxidants are more active in emulsions than their hydrophilic homologues, thus assuming a linear dependency between hydrophobicity and antioxidant capacity. In contrast, we formulate in this paper an alternative hypothesis assuming a possible nonlinear dependency. To verify this so-called "nonlinear hypothesis", the antioxidant capacity of a homologous series of rosmarinic acid and its alkyl esters (methyl, butyl, octyl, dodecyl, hexadecyl, octadecyl, and eicosyl) was evaluated using a newly developed conjugated autoxidizable triene (CAT) assay. It appeared that the antioxidant capacity increases as the alkyl chain is lengthened, with a maximum for the octyl chain, after which further chain extension leads to a collapse in antioxidant capacity. This nonlinear effect was discussed in relation to the "cutoff effect" generally observed in studies using cultured cells. This new hypothesis may provide a better understanding of the antioxidant behavior of phenolics in emulsion which is a key to develop new antioxidant strategies to protect lipid substrates from oxidation. Moreover, the lipophilization with medium chain appeared as a promising way to enhance the antioxidant capacity of phenolics since octyl rosmarinate was three times more effective than rosmarinic acid which is already one of the most powerful known phenolic antioxidant. Finally, this work paves the way for systematic investigation of the chain length effect to design new "phenolipids" in a rational fashion.