Relationship between Hydrophobicity and Antioxidant Ability of “Phenolipids” in Emulsion: A Parabolic Effect of the Chain Length of Rosmarinate Esters

Abstract

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.

Rosmarinic acid content in basil plants grown in vitro and in hydroponics

“…In vitro studies showed that the antioxidant capacity of RA alkyl derivatives could be higher than RA [32], and further work is in progress to more thoroughly characterize the methylated form of RA and to verify whether its production is a result of genuine biosynthesis or artifactual methylation during methanol extraction.…”

The antioxidative effect of lipophilized rutin and dihydrocaffeic acid in fish oil enriched milk

“…Thus, the results lead to the conclusion that lipophilization with medium chain fatty acids is a promising way to increase the antioxidant activity [16]. However, the results obtained with chlorogenate and rosmarinate esters have also led to the suggestion that the exact location of antioxidants in the discontinuous phase, interfacial layer or oil droplets, is important for the activity of the antioxidants [11,16]. In addition, a study on lipophilized dihydrocaffeic acids and their antioxidative effect in o/w emulsions reported by Sørensen et al [17] suggested that lipophilized dihydrocaffeic acid tended to follow the newly suggested cut-off effect in relation to the alkyl chain length attached although only two chain lengths were evaluated.…”

“…The current work in this area has been summarized by Shahidi and Zhong [15]. Laguerre et al [11,16] have recently reported on the antioxidative effect of lipohilized chlorogenic and rosmarinic acids. For chlorogenic acid the antioxidant capacity increased as the alkyl chain length was increased from 1 to 12 carbon atoms, whereas further increase of the chain length resulted in a drastic decrease in the antioxidant capacity.…”

“…For rosmarinate esters, the octyl rosmarinate improved the antioxidative effect eight times compared to rosmarinic acid. Thus, the results lead to the conclusion that lipophilization with medium chain fatty acids is a promising way to increase the antioxidant activity [16]. However, the results obtained with chlorogenate and rosmarinate esters have also led to the suggestion that the exact location of antioxidants in the discontinuous phase, interfacial layer or oil droplets, is important for the activity of the antioxidants [11,16].…”

Are emerging deep eutectic solvents (DES) relevant for lipase-catalyzed lipophilizations?

“…In that sense, the lipophilization reactions are particularly advantageous and effective, and may be seen as a vectorization key unlocking the lipid barrier encountered by the bioactive molecule while maintaining its original functional properties. In the case of phenolic acids, the methods commonly used consists in attaching on the reactive carboxyl group, either a single or double tail lipophilic domain (usually an aliphatic with a different carbon backbone) resulting in new molecule with emulsifying properties, and often greatly improved antioxidant activity (Durand et al, 2015;Laguerre et al, 2010). This reaction can be performed on simple phenolic acids derived from benzoic acid (hydroxybenzoic acids), cinnamic (hydroxycinnamic acids) or more complex polyphenolic acids such as chlorogenic acid and rosmarinic acid with single or double tail (Fig.…”