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

Dinh Hieu Truong; Thi Chinh Ngo; Nguyen Thi Ai Nhung; Duong Tuan Quang; Thi Le Anh Nguyen; Dorra Khiri; Sonia Taamalli; Florent Louis; Abderrahman El Bakali; Duy Quang Dao

doi:10.1039/d1ra07599c

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

RSC Adv. 2022 Jan 10;12(3):1499-1514. doi: 10.1039/d1ra07599c. eCollection 2022 Jan 5.

Authors

Dinh Hieu Truong^{1

2}, Thi Chinh Ngo^{1

2}, Nguyen Thi Ai Nhung³, Duong Tuan Quang³, Thi Le Anh Nguyen^{1

2}, Dorra Khiri⁴, Sonia Taamalli⁴, Florent Louis⁴, Abderrahman El Bakali⁴, Duy Quang Dao^{1

2}

Affiliations

¹ Institute of Research and Development, Duy Tan University Da Nang 550000 Vietnam daoduyquang@duytan.edu.vn.
² Faculty of Natural Sciences, Duy Tan University Da Nang 550000 Vietnam.
³ Department of Chemistry, University of Sciences, Hue University Hue 530000 Vietnam.
⁴ Department of Chemistry, University of Education, Hue University Hue 530000 Vietnam.

Abstract

Direct and indirect antioxidant activities of rosmarinic acid (RA) based on HOO˙/CH₃OO˙ 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 × 10³ M^-1 s^-1 (HOO˙) and 4.49 × 10³ M^-1 s^-1 (CH₃OO˙) 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 Δ_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˙ 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.