Mactanamide and lariciresinol as radical scavengers and Fe2+ion chelators - A DFT study

A DFT based kinetic study of center dot OOH radical scavenging potency of mactanamide (MA) and lariciresinol (LA), two natural polyphenols, indicates their nearly equal potential via the proton coupled electron transfer (PCET) mechanism in lipid media. Contribution of C-H bond breaking to this potency is negligible compared to O-H bond breaking, contrary to recent claims. The predicted potency of both compounds is not sufficient to protect biological molecules from oxidative damage in lipid media. In aqueous media, the scavenging potency of MA and LA phenoxide anions via the single electron transfer (SET) mechanism is much higher and may contribute to the protection of lipids, proteins, and DNA from center dot OOH radical damage. Also, MA and LA have the potential to chelate catalytic Fe2+ ions, thus suppressing the formation of dangerous center dot OH radicals via Fenton-type reactions. The monoanionic species of MA and LA show stronger monodentate chelating ability with Fe2+ ion compared to its neutral form. The dianionic specie LA2-exhibited the highest chelation ability with Fe2+ ion via bidentate 1:2 coordination. However, direct radical scavenging and metal chelation could be rarely operative in vivo because MA and LA presumably achieve very low concentrations in systemic circulation.

Automated summary

A DFT-based kinetic study reveals that mactanamide (MA) and lariciresinol (LA), two natural polyphenols, possess similar center dot OOH radical scavenging potency in lipid media through the proton coupled electron transfer (PCET) mechanism. Contrary to recent claims, the contribution of C-H bond breaking to this potency is negligible. Nevertheless, the predicted potency of both compounds is insufficient to protect biological molecules from oxidative damage in lipid media. In aqueous media, MA and LA phenoxide anions exhibit much higher scavenging potency via the single electron transfer (SET) mechanism, contributing to the protection of lipids, proteins, and DNA from center dot OOH radical damage. Additionally, MA and LA are capable of chelating catalytic Fe2+ ions, thereby inhibiting the formation of dangerous center dot OH radicals through Fenton-type reactions.