Antioxidant Activity of Magnolol and Honokiol: Kinetic and Mechanistic Investigations of Their Reaction with Peroxyl Radicals

Abstract

Magnolol and honokiol, the bioactive phytochemicals contained in Magnolia officinalis, are uncommon antioxidants bearing isomeric bisphenol cores substituted with allyl functions. We have elucidated the chemistry behind their antioxidant activity by experimental and computational methods. In the inhibited autoxidation of cumene and styrene at 303 K, magnolol trapped four peroxyl radicals, with a kinh of 6.1 × 10(4) M(-1) s(-1) in chlorobenzene and 6.0 × 10(3) M(-1) s(-1) in acetonitrile, and honokiol trapped two peroxyl radicals in chlorobenzene (kinh = 3.8 × 10(4) M(-1) s(-1)) and four peroxyl radicals in acetonitrile (kinh = 9.5 × 10(3) M(-1) s(-1)). Their different behavior arises from a combination of intramolecular hydrogen bonding among the reactive OH groups (in magnolol) and of the OH groups with the aromatic and allyl π-systems, as confirmed by FT-IR spectroscopy and DFT calculations. Comparison with structurally related 3,3',5,5'-tetramethylbiphenyl-4,4'-diol, 2-allylphenol, and 2-allylanisole allowed us to exclude that the antioxidant behavior of magnolol and honokiol is due to the allyl groups. The reaction of the allyl group with a peroxyl radical (C-H hydrogen abstraction) proceeds with rate constant of 1.1 M(-1) s(-1) at 303 K. Magnolol and honokiol radicals do not react with molecular oxygen and produce no superoxide radical under the typical settings of inhibited autoxidations.

Magnolol: A Neolignan from the Magnolia Family for the Prevention and Treatment of Cancer

“…MAG is reported to possess an array of pharmacological effects including anti-oxidant [70], anti-inflammatory [71], anti-bacterial [10], anti-thrombotic or anti-platelet [72], anti-stress [73], anti-anxiety, anti-Alzheimer [74], anti-stroke [75], hypoglycemic [76], smooth muscle relaxant [77,78], weight control [79], anti-dyspeptic/prokinetic [80], anti-epileptic [81], and hepatoprotective effects [82]. Small-scale clinical studies on MAG and its interaction with gamma-aminobutyric acid-A (GABA-A) and muscarinic receptors show that it helps in decreasing the anxiety levels in patients [78,83,84,85].…”

Ditocopheryl Sulfides and Disulfides: Synthesis and Antioxidant Profile

“…For this reason, in Table ditocopheryl sulfides have two distinct values of k inh and n , referred to the strong and to the weak inhibition, respectively. This bimodal inhibition, which has been previously observed in the case of other bisphenols, such as magnolol, is due to the fact that the two phenolic moieties react in sequence, and that the oxidation of the former negatively influences the reactivity of the latter by formation of strong intramolecular H‐bonds . The reason why this does not occur with tocopheryl disulfides is reasonably related to the presence of a different H‐bond network compared to sulfides (see discussion below).…”

The Role of Onium Salts in the Pro‐Oxidant Effect of Gold Nanoparticles in Lipophilic Environments

“…The autoxidation experiments were performed in a two‐channel oxygen uptake apparatus, based on a Validyne DP 15 differential pressure transducer built in our laboratory . In a typical experiment, an air‐saturated mixture of styrene and chlorobenzene, 1:1 (v/v), containing the initiator, was equilibrated with an identical reference solution containing an excess of TOH.…”

“…The oxygen consumption in the sample was measured after calibration of the apparatus from the differential pressure recorded with time between the two channels. The initiation rates R i , were determined for each condition by the inhibitor method by using TOH as a reference antioxidant and Equation (4) . The pro‐oxidant activity was determined by measuring R i in the presence of t BuOOH (1–5 m m ), t BuOO t Bu (1–5 m m ), or AIBN (50 m m ), and variable concentration of the AuNPs, C 12 H 25 SH (0.045–0.38 m m ), or the onium salts TOAB, Oct 4 NBF 4 , Hex 4 NBF 4 , and Hex 4 NPF 6 .…”