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Chemistry Letters Vol.36, No.10 (2007)
Involvement of Electron Transfer in the Radical-scavenging Reaction of Resveratrol
Ikuo Nakanishi,ꢀ1;2 Tomokazu Shimada,3;4 Kei Ohkubo,2 Sushma Manda,1 Takehiko Shimizu,3;4
Shiro Urano,3 Haruhiro Okuda,4 Naoki Miyata,5 Toshihiko Ozawa,1;6 Kazunori Anzai,1
Shunichi Fukuzumi,2 Nobuo Ikota,7 and Kiyoshi Fukuharaꢀ4
1Radiation Modifier Team, Heavy-Ion Radiobiology Research Group, Research Center for Charged Particle Therapy,
National Institute of Radiological Sciences (NIRS), Inage-ku, Chiba 263-8555
2Department of Material and Life Science, Graduate School of Engineering, Osaka University, SORST,
Japan Science and Technology Agency (JST), Suita, Osaka 565-0871
3Department of Applied Chemistry, Shibaura Institute of Technology, Koto-ku, Tokyo 135-8548
4Division of Organic Chemistry, National Institute of Health Sciences (NIHS), Setagaya-ku, Tokyo 158-8501
5Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603
6Yokohama College of Pharmacy, Yokohama 245-0066
7School of Pharmacy, Shujitsu University, Okayama 703-8516
(Received August 3, 2007; CL-070831; E-mail: nakanis@nirs.go.jp)
Resveratrol (3,40,5-trihydroxy-trans-stilbene) efficiently
scavenges an oxygen radical via an electron transfer from resver-
atrol to the radical in deaerated acetonitrile, which is significant-
ly accelerated by the presence of magnesium ion.
1.2
1.0
0.8
0.6
0.4
0.2
0
Resveratrol (1H, 3,40,5-trihydroxy-trans-stilbene), one of
polyphenols found in grapes, has attracted considerable interest
because of its antioxidative potential. 1H has reported to inhibit
the oxidation of human low-density lipoprotein (LDL) and re-
duce the propensity of human plasma and LDL to undergo lipid
peroxidation.1,2 Furthermore, it has been reported that 1H inhib-
its cellular events associated with tumor initiation, promotion,
and progression.3 Besides its beneficial effects, 1H was also
shown to induce genotoxicity through a high frequency of
micronucleus and sister chromatid exchange in vitro and
DNA-cleaving activity in the presence of CuII.4,5 However, very
little is known about the detailed mechanism of antioxidative as
well as toxic action of 1H. On the other hand, two mechanisms
are known for the antioxidative radical-scavenging reactions of
polyphenols: a one-step hydrogen atom transfer from the phenol-
ic OH group; and an electron transfer followed by a proton trans-
fer.6–8 Metal ions are a powerful tool that can be used to distin-
guish between these two mechanisms, since electron-transfer
reactions are known to be significantly accelerated by their
presence.9 We report herein that the scavenging reaction of
galvinoxyl radical (GOꢁ), a relatively stable oxygen radical, by
1H is significantly accelerated by the presence of magnesium
ion in deaerated acetonitrile (MeCN). The detailed kinetic data
obtained in this study provides valuable information about the
antioxidative mechanism of 1H, leading to the development
of novel antioxidants with enhanced antioxidative abilities and
reduced toxicity.
300
400
500
Wavelength / nm
Figure 1. Spectral change observed in the reaction of 1H
(1:3 ꢃ 10ꢂ4 mol dmꢂ3) with GOꢁ (8:0 ꢃ 10ꢂ6 mol dmꢂ3) in dea-
erated MeCN at 298 K (interval: 600 s).
concentration. The pseudo-first-order rate constants (kobs) in-
crease with increasing [1H], exhibiting first-order dependence
on [1H]. From the slope of the linear plot of kobs vs. [1H], the
second-order rate constant (k) was determined for the radical-
scavenging reaction as 4.1 dm3 molꢂ1 sꢂ1 in deaerated MeCN
at 298 K. This k value is significantly smaller than those of rep-
resentative natural phenolic antioxidants, such as (+)-catechin
10
(2:6 ꢃ 10 dm3 molꢂ1 sꢂ1
)
and a vitamin E model (3:0 ꢃ 103
dm3 molꢂ1 sꢂ1).11
If the radical-scavenging reaction by 1H involves an elec-
tron-transfer process as the rate-determining step, the rates of
radical scavenging would be accelerated by the presence of met-
al ions.12–14 This was investigated by examining the effect of
Mg(ClO4)2 on the radical-scavenging rate by 1H in deaerated
MeCN. When Mg(ClO4)2 is added to the 1H–GOꢁ system in dea-
erated MeCN, the rate of GOꢁ-scavenging reaction by 1H was
significantly accelerated. The k values increase linearly with
increasing concentration of Mg(ClO4)2 as shown in Figure 2.
It should be noted that there is no interaction between GOꢁ and
Mg2þ, since no spectral change was observed in the presence
of a large amount of Mg2þ. Thus, the radical-scavenging
reaction may proceed via an electron transfer from 1H to GOꢁ,
which is accelerated by the presence of Mg2þ, followed by
proton transfer from 1Hꢁþ to GOꢂ as shown in Scheme 1. In
such a case, the coordination of Mg2þ to GOꢂ may stabilize
Upon addition of 1H to a deaerated MeCN solution of GOꢁ,
the absorption band at 428 nm due to GOꢁ disappeared immedi-
ately as shown in Figure 1. This spectral change suggests that 1H
can efficiently scavenge GOꢁ. The rate of the GOꢁ-scavenging re-
action by 1H was measured by monitoring the decrease in ab-
sorbance at 428 nm due to GOꢁ using a photodiode array spectro-
photometer. The decay of the absorbance at 428 nm due to GOꢁ
obeyed pseudo-first-order kinetics when the concentration of 1H
([1H]) was maintained at more than a 10-fold excess of the GOꢁ
Copyright Ó 2007 The Chemical Society of Japan
Nakanishi, Ikuo
