New insights into the competition between antioxidant activities and pro-oxidant risks of rosmarinic acid

Direct and indirect antioxidant activities of rosmarinic acid (RA) based on HOO center dot/CH3OO center dot radical scavenging and Fe(iii)/Fe(ii) ion chelation were theoretically studied using density functional theory at the M05-2X/6-311++G(2df,2p) level of theory. First, four antioxidant mechanisms including hydrogen atom transfer (HAT), radical adduct formation (RAF), proton loss (PL) and single electron transfer (SET) were investigated in water and pentyl ethanoate (PEA) phases. Regarding the free radical scavenging mechanism, HAT plays a decisive role with overall rate coefficients of 1.84 x 10(3) M-1 s(-1) (HOO center dot) and 4.49 x 10(3) M-1 s(-1) (CH3OO center dot) in water. In contrast to PL, RAF and especially SET processes, the HAT reaction in PEA is slightly more favorable than that in water. Second, the [Fe(iii)(H2O)(6)](3+) and [Fe(ii)(H2O)(6)](2+) ion chelating processes in an aqueous phase are both favorable and spontaneous especially at the O5, site-1, and site-2 positions with large negative Delta(r)G(0) values and great formation constant K-f. Finally, the pro-oxidant risk of RA(-) was also considered via the Fe(iii)-to-Fe(ii) complex reduction process, which may initiate Fenton-like reactions forming reactive HO center dot radicals. As a result, RA(-) does not enhance the reduction process when ascorbate anions are present as reducing agents, whereas the pro-oxidant risk becomes remarkable when superoxide anions are found. The results encourage further attempts to verify the speculation using more powerful research implementations of the antioxidant activities of rosmarinic acid in relationship with its possible pro-oxidant risks.

Automated summary

In this study, the direct and indirect antioxidant activities of rosmarinic acid (RA) were theoretically investigated. The results showed that RA acts primarily through hydrogen atom transfer mechanism and exhibits slightly higher antioxidant activity in the PEA phase compared to the water phase. Additionally, RA can chelate with Fe(iii) and Fe(ii) ions in the aqueous phase. However, it also has a pro-oxidant risk in the presence of superoxide anions.