Effects of magnesium ion on kinetic stability and spin distribution of phenoxyl radical derived from a vitamin E analogue: Mechanistic insight into antioxidative hydrogen-transfer reaction of vitamin E

Article abstract of DOI:10.1039/b205380b

The phenoxyl radical 1^. of a vitamin E analogue, generated by the reaction of 2,2,5,7,8-pentamethylchroman-6-ol (1H) with 2,2-di(4-tert-octylphenyl)-1-picrylhydrazyl (DPPH^.) or galvinoxyl (G^.), was significantly stabilized by the presence of Mg²⁺. Addition of Mg²⁺ into a solution of 1^. resulted in a red shift of the absorption band of 1^. as well as a decrease in the g value of the EPR spectrum of 1^., indicating a complex formation between 1^. and Mg²⁺. The complexation between the phenoxyl radical and Mg²⁺ significantly retards the disproportionation reaction of 1^. by electronic repulsion between the metal cation and a generated organic cation (1⁺), leading to stabilization of the organic radical species. No effect of Mg²⁺ on the rate of hydrogen atom transfer from 1H to DPPH^. or to G^. was observed, suggesting that the hydrogen-transfer reaction between 1H and DPPH^. or G^. proceeds via a one-step hydrogen atom transfer mechanism rather than electron-transfer followed by proton transfer.

Full text of DOI:10.1039/b205380b

View Article Online / Journal Homepage / Table of Contents for this issue
Effects of magnesium ion on kinetic stability and spin distribution
of phenoxyl radical derived from a vitamin E analogue:
mechanistic insight into antioxidative hydrogen-transfer
reaction of vitamin E†
2
a
b
b,c
d
e
Ikuo Nakanishi,* Kiyoshi Fukuhara,* Tomokazu Shimada, Kei Ohkubo, Yuko Iizuka,
e
e
c
f
g
Keiko Inami, Masataka Mochizuki, Shiro Urano, Shinobu Itoh, Naoki Miyata and
Shunichi Fukuzumi*
d
a
Redox Regulation Research Group, Research Center for Radiation Safety,
National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555, Japan.
E-mail: nakanis@nirs.go.jp; Fax: ϩ81-43-255-6819; Tel: ϩ81-43-206-3131
Division of Organic Chemistry, National Institute of Health Sciences, Setagaya-ku,
Tokyo 158-8501, Japan
Department of Applied Chemistry, Shibaura Institute of Technology, Minato-ku,
Tokyo 108-8548, Japan
Department of Material and Life Science, Graduate School of Engineering, Osaka University,
CREST, Japan Science and Technology Corporation, Suita, Osaka 565-0871, Japan
Division of Organic and Bioorganic Chemistry, Kyoritsu College of Pharmacy, Minato-ku,
Tokyo 105-8512, Japan
Department of Chemistry, Graduate School of Science, Osaka City University, Sumiyoshi-ku,
Osaka 558-8585, Japan
b
c
d
e
f
g
Department of Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences,
Nagoya City University, Mizuho-ku, Nagoya 467-8603, Japan
Received (in Cambridge, UK) 5th June 2002, Accepted 20th June 2002
First published as an Advance Article on the web 15th July 2002
ؒ
The phenoxyl radical 1 of a vitamin E analogue, generated by the reaction of 2,2,5,7,8-pentamethylchroman-6-ol
ؒ
ؒ
(
1H) with 2,2-di(4-tert-octylphenyl)-1-picrylhydrazyl (DPPH ) or galvinoxyl (G ), was significantly stabilized by the
2ϩ 2ϩ
ؒ
ؒ
presence of Mg . Addition of Mg into a solution of 1 resulted in a red shift of the absorption band of 1 as well
as a decrease in the g value of the EPR spectrum of 1 , indicating a complex formation between 1 and Mg . The
complexation between the phenoxyl radical and Mg significantly retards the disproportionation reaction of 1 by
electronic repulsion between the metal cation and a generated organic cation (1 ), leading to stabilization of the
organic radical species. No effect of Mg on the rate of hydrogen atom transfer from 1H to DPPH or to G was
observed, suggesting that the hydrogen-transfer reaction between 1H and DPPH or G proceeds via a one-step
ؒ
ؒ
2ϩ
2
ϩ
ؒ
ϩ
2ϩ
ؒ
ؒ
ؒ
ؒ
hydrogen atom transfer mechanism rather than electron-transfer followed by proton transfer.
Introduction
reaction of α-TOH with peroxyls exhibits a substantial deu-
terium kinetic isotope effect (k /k = 5.4 ± 0.4), indicating that
H
D
Vitamin E (α-tocopherol, α-TOH) is a very effective biological
antioxidant that can scavenge peroxyl radicals in biological
membranes, preventing oxidative injury by toxic and carcino-
genic chemicals. It has been suggested that α-TOH traps rad-
icals by hydrogen atom transfer from its phenolic OH group to
form the corresponding phenoxyl radical species, α-TO ,
which readily decomposes, leading to a wide variety of oxid-
ation products of α-tocopherol. However, very little is known
about the elementary steps of the oxidation reaction of α-TOH.
There are two possibilities in the mechanisms of oxidation
reactions, i.e., a one-step hydrogen atom transfer or electron
26
the hydrogen atom transfer is rate controlling. Mukai et al.
have also demonstrated that the antioxidant activity of toco-
pherol compounds relates to the total electron-donating char-
1–3
27
acter of the alkyl group substituents on the aromatic ring.
Thus, it is still not clear whether the hydrogen-transfer reaction
of α-TOH proceeds via a one-step hydrogen transfer or electron
transfer followed by proton transfer. It has been reported
ؒ
1–3
4–21
2ϩ
that the effect of Mg on the hydrogen-transfer rates from
NADH (dihydronicotinamide adenine dinucleotide) analogues
to aminoxyl or nitrogen radicals provides a reliable criterion for
distinguishing between the one-step hydrogen atom transfer
22–24
transfer followed by proton transfer.
proposed that a first step in the antioxidative activity of toco-
pherol produces a cation radical by one electron extraction.
On the other hand, Burton and Ingold have reported that the
Svanholm et al. have
28
and the electron-transfer mechanisms. It has also been demon-
2ϩ
2ϩ
strated that metal ions such as Mg and Ca can stabilize
25
29
phenoxyl radicals by forming complexes. In this context, the
effects of metal ions on the oxidation reaction of α-TOH would
be of significant interest to elucidate the mechanistic aspect of
the antioxidative reactions of vitamin E.
†
Electronic supplementary information available: calculated spin
2ϩ
ؒ
We report herein that a phenoxyl radical (1 ) of a vitamin E
density distributions and dependence of kHT on [Mg ] for hydrogen
transfer. See http://www.rsc.org/suppdata/p2/b2/b205380b/
analogue, 2,2,5,7,8-pentamethylchroman-6-ol (1H), generated
1
520
J. Chem. Soc., Perkin Trans. 2, 2002, 1520–1524
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b205380b

View Article Online
3
0
in the reaction of 1H with 2,2-di(4-tert-octylphenyl)-1-picryl-
those vs. SCE by adding 0.29 V. All electrochemical measure-
ments were carried out at 298 K under an atmospheric pressure
of argon.
ؒ
ؒ
hydrazyl (DPPH ) or galvinoxyl (G ) is significantly stabilized
2
ϩ
2ϩ
by interaction with Mg . The electronic structure of the Mg –
ؒ
1
complex thus generated has been well characterized by EPR.
Detailed spectroscopic and kinetic analyses on the 1H–DPPH
G )–Mg system provide a valuable insight into the mechan-
ؒ
Theoretical calculations
ؒ
2ϩ
(
Density functional calculations were performed on a COMPAQ
DS20E computer using the Amsterdam Density Functional
ADF) program version 1999.02 developed by Baerends et al.
The electronic configurations of the molecular systems were
described by an uncontracted triple-ζ Slater-type orbital basis
set (ADF basis set IV) with a single polarization function used
for each atom. Core orbitals were frozen through 1s (C, O) and
p (Mg). The calculations were performed using the local
exchange-correlation potential by Vosko et al. and the non-
local gradient corrections by Becke and Perdew during the
geometry optimizations. First-order scalar relativistic corre-
lations were added to the total energy. Final geometries and
energetics were optimized by using the algorithm of Versluis
ism of the hydrogen transfer reactions of a vitamin E analogue
ؒ
to determine whether the reaction between 1H and DPPH
31
(
ؒ
or G proceeds via a one-step hydrogen atom transfer or via
electron transfer.
Experimental
2
32
Materials
33 34
2
,2,5,7,8-Pentamethylchroman-6-ol (1H) was purchased
from Wako Pure Chemical Ind. Ltd., Japan. 2,2-Bis(4-tert-
ؒ
ؒ
octylphenyl)-1-picrylhydrazyl (DPPH ) and galvinoxyl (G )
were obtained commercially from Aldrich. Mg(ClO4)2 and
acetonitrile (MeCN; spectral grade) were purchased from
Nacalai Tesque, Inc., Japan and used as received.
35
and Ziegler provided in the ADF package and were con-
sidered converged when the changes in bond lengths between
subsequent iterations fell below 0.01 Å.
Spectral and kinetic measurement
Results and discussion
Ϫ2
Typically, an aliquot of 1H (2.0 × 10 M) in deaerated MeCN
was added to a quartz cuvette (10 mm i.d.) which contained
Stabilization of phenoxyl radical of a vitamin E analogue by
magnesium ion
ؒ
Ϫ5
DPPH (1.4 × 10 M) in deaerated MeCN (3.0 ml). This led to
ؒ
a hydrogen-transfer reaction from 1H to DPPH . UV–VIS
When 1H was added to a deaerated acetonitrile (MeCN) sol-
spectral changes associated with this reaction were monitored
using a Hewlett-Packard 8453 photo diode array spectro-
photometer. The rates of hydrogen transfer were determined by
ؒ
ution of DPPH , the visible absorption band at 543 nm due to
ؒ
DPPH immediately decreased, accompanied by an increase in
ؒ
the absorption bands at 402 and 423 nm with clear isosbestic
points at 343, 374, and 437 nm as shown in Fig. 1. The absorp-
monitoring the absorbance change at 543 nm due to DPPH
(
4
3
Ϫ1
Ϫ1
ε = 1.18 × 10 dm mol cm ). Pseudo-first-order or second-
order rate constants were determined by a least-squares curve
fit using an Apple Macintosh personal computer. The first-
order plots of ln(A Ϫ A) vs. time and the second-order plots of
∞
Ϫ1
(
A Ϫ A) vs. time (A and A refer to the final absorbance and
∞
∞
the absorbance at the reaction time, respectively) were linear
until three or more half-lives with the correlation coefficient ρ >
ؒ
0
.999. The reaction of 1H with G was carried out in the same
manner and the rates were determined from the absorbance
ؒ
5
3
Ϫ1
Ϫ1
change at 428 nm due to G (ε = 1.43 × 10 dm mol cm ).
EPR measurements
Ϫ3
Typically, an aliquot of a stock solution of 1H (1.0 × 10 M)
was added to a LABOTEC LLC-04B EPR sample tube con-
ؒ
Ϫ3
taining a deaerated MeCN solution of DPPH (1.0 × 10 M)
in the presence or absence of 0.1 M Mg(ClO4)2 under an
atmospheric pressure of Ar. EPR spectra of the phenoxyl
ؒ
ؒ
radical 1 produced in the reaction between 1H and DPPH
Ϫ4
Fig. 1 Spectral changes in the reaction of 1H (7.5 × 10 M) with
were taken on a JEOL X-band spectrometer (JES-FA100). The
EPR spectra were recorded under nonsaturating microwave
power conditions. The magnitude of modulation was chosen to
optimize the resolution and the signal-to-noise (S/N) ratio of
the observed spectra. The g values and the hyperfine coupling
constants were calibrated with a Mn marker. Computer sim-
ulation of the EPR spectra was carried out using Calleo ESR
Version 1.2 program (Calleo Scientific Publisher) on an Apple
Macintosh personal computer.
ؒ
Ϫ5
DPPH (1.4 × 10 M) in deaerated MeCN at 298 K (2 s interval).
Inset: Plot of kobs vs. [1H].
tion bands around 400 nm and the broad band around 530 nm
are typical for phenoxyl radical species of α-tocopherol. This
indicates that hydrogen atom transfer from 1H to DPPH
occurs to produce the corresponding phenoxyl radical 1 and
DPPH [eqn. (1)]. In fact, the EPR spectrum having a g value of
.0047 due to 1 was observed in the reaction of 1H with
DPPH in deaerated MeCN at 298 K as shown in Fig. 2(a). The
EPR signal of 1 gradually decreased with prolonged reaction
time. The observed hyperfine structure in Fig. 2(a) is well
reproduced by the computer simulation with the hyperfine
splitting (hfs) values of one set of methylene protons (1.39 G)
and three sets of methyl protons (5.87, 4.40 and 0.86 G). Based
36
2ϩ
ؒ
ؒ
2
ؒ
2
ؒ
Cyclic voltammetry
ؒ
37
The cyclic voltammetry measurements were performed on a
BAS 100 W electrochemical analyzer in deaerated MeCN con-
taining 0.10 M NBu ClO as a supporting electrolyte. The Pt
working electrode (BAS) was polished with BAS polishing
alumina suspension and rinsed with acetone before use. The
counter electrode was a platinum wire. The measured potentials
4
4
ؒ
37d
on the reported hfs values for 1 in benzene
as well as
ؒ
the calculated spin density of 1 by the Amsterdam Density
Functional (ADF) method (see Experimental section), we
assigned those hfs values as shown in Table 1.
were recorded with respect to an Ag/AgNO (0.01 M) reference
electrode. The E1/2 values (vs. Ag/AgNO ) were converted to
3
3
J. Chem. Soc., Perkin Trans. 2, 2002, 1520–1524
1521

View Article Online
ؒ
ؒ
Table 1 g Values and hyperfine splitting (hfs) values (in G) of 1 and
ascribed to a hydrogen atom transfer from 1H to G [eqn.
2ϩ
ؒ
Mg -1 in deaerated MeCN
ؒ
(
2)]. The rate constant for hydrogen transfer from 1H to G
was determined in the same manner as in the case of DPPH as
.0 × 10 M s , which is about 6-fold larger than that deter-
mined for DPPH . Although the absorption bands at 402 and
423 nm due to 1 generated by hydrogen transfer from 1H to G
could not be observed because of the overlap with the large
absorption band at 428 nm due to G , the formation of 1 can
be confirmed from its EPR spectrum.
ؒ
5
7
8
4
Radical
g
a(3H )
a(3H )
a(3H )
a(2H )
3
Ϫ1 Ϫ1
3
ؒ
ؒ
ؒ
1
2.0047
2.00476
2.0040
5.87a
4.40a
0.86a
1.39a
ؒ
ؒ
a
a
1
6.04
4.55
0.96
1.48
2ϩ
ؒ
Mg -1
3.35
—
4.86
—
ؒ
ؒ
a
Taken from ref 37d (in benzene).
(
2)
ؒ
The phenoxyl radical (1 ) generated by hydrogen transfer
ؒ
from 1H to DPPH gradually decomposed at room temperature
36
(
Fig. 3(a)). The decrease in the absorption band at 423 nm due
ؒ
Fig. 2 (a) EPR spectrum of 1 generated in the reaction of 1H
Ϫ3
ؒ
Ϫ3
(
1.0 × 10 M) with DPPH (1.0 × 10 M) in deaerated MeCN
2ϩ
ؒ
at 298 K; (b) EPR spectrum of the Mg –1 complex generated in
Ϫ3
ؒ
Ϫ3
the reaction of 1H (1.0 × 10 M) with DPPH (1.0 × 10 M) in the
presence of 0.1 M Mg(ClO ) in deaerated MeCN at 298 K.
4
2
Fig. 3 (a) Time course of the absorption change at 423 nm due to
ؒ
Ϫ4
ؒ
1
(black circles) in the reaction of 1H (7.5 × 10 M) with DPPH
Ϫ5
(
1.4 × 10 M) in deaerated MeCN at 298 K. (b) Time course of
2ϩ
ؒ
the absorption change at 437 nm due to the Mg -1 complex (black
Ϫ4
ؒ
triangles) in the reaction of 1H (7.5 × 10
M) with DPPH
Ϫ5
(
1.4 × 10 M) in the presence of 0.1 M Mg(ClO ) in deaerated MeCN
4
2
at 298 K.
ؒ
to 1 obeys second-order kinetics in agreement with the decay
occurring via a bimolecular disproportionation reaction to give
1
H and the corresponding quinone methide (2) as shown
29,36
in Scheme 1.
The second-order rate constant (kdec) for
(
1)
ؒ
The decrease in the absorbance at 543 nm due to DPPH
obeyed pseudo-first-order kinetics under conditions where the
concentration of 1H was maintained at more than a 10-fold
ؒ
excess of DPPH concentration. The pseudo-first-order rate
constant (kobs) increases linearly with an increase in concen-
tration of 1H as shown in the inset of Fig. 1. From the slope of
the linear plot of kobs vs. [1H] the second-order rate constant for
ؒ
hydrogen transfer (k ) from 1H to DPPH was obtained as
5
HT
2
Ϫ1 Ϫ1
.1 × 10 M s . This value is nearly the same as the k value
HT
2 Ϫ1 Ϫ1
(
4.9 × 10
M
s ) reported for hydrogen transfer from
38
ؒ
ؒ
α-tocopherol to DPPH in MeCN. When DPPH was replaced
ؒ
by the galvinoxyl radical (G ), the decay of the absorption band
at 428 nm due to G was observed upon addition of 1H to a
deaerated MeCN solution of G . Such spectral change can be
ؒ
ؒ
Scheme 1
1
522
J. Chem. Soc., Perkin Trans. 2, 2002, 1520–1524

View Article Online
ؒ
the decomposition of 1 in deaerated MeCN at 298 K was
3
Ϫ1 Ϫ1 39
determined from the second-order plot as 2.7 × 10 M s .
In the presence of Mg(ClO ) (0.1 M), the reaction between
4
2
ؒ
1
H and DPPH also took place to give the phenoxyl rad-
ical species in deaerated MeCN, the absorption bands of
which, however, were shifted from 402 and 423 nm to 412 and
4
37 nm, respectively. It should be noted that no decay of
these absorption bands was observed, demonstrating signifi-
cantly the enhanced stability of the phenoxyl radical species in
the presence of Mg(ClO ) (Fig. 3(b)). Since the dispropor-
4
2
ؒ
tionation reaction between the two molecules of 1 involves
both oxidation and reduction, 1 must act as both the oxidant
and reductant (Scheme 1). Although the complexation of the
ؒ
29
2ϩ
ؒ
Lewis acid such as Mg with 1 would accelerate the reduction
ؒ
Ϫ
of 1 to the phenolate 1 , it would decelerate the oxidation
process due to the repulsive interaction between the oxidized
ϩ
2ϩ
29
product 1 aϩnd Mg at the same time. Thus, the destabil-
2ϩ
ization of 1 by Mg governs the overall reactivity in the
disproportionation reaction to stabilize the phenoxyl radical
ؒ
2ϩ
species 1 in the presence of Mg .
Effects of magnesium ion on the spin distribution of the phenoxyl
radical
2
ϩ
ؒ
Fig. 4 Plot of the rate constant of hydrogen transfer from 1H or
The EPR spectrum of the Mg complex of 1 generated in the
ؒ
ؒ
AcrH to DPPH or G (logk ) vs. the free energy of electron transfer
ؒ
2
HT
reaction of 1H with DPPH in the presence of 0.1 M Mg(ClO )
in deaerated MeCN is observed as shown in Fig. 2(b). The g
value of the EPR spectrum of Mg –1 is determined as 2.0040,
which is appreciably smaller than the g value of 1 (2.0047). The
smaller g value of Mg –1 (2.0040) than that of 1 (2.0047)
indicates that the spin density on oxygen nuclei in Mg –1
is decreased by complexation with Mg . The hyperfine
structure can be reproduced by computer simulation with the
ؒ
ؒ
0
4
2
from 1H or AcrH to DPPH or G (∆G et). The solid line shows the
dependence of the calculated rate constant of electron transfer (k ) on
∆G based on eqn. (3), see text.
2
et
2ϩ
ؒ
0
et
ؒ
2ϩ
ؒ
ؒ
electron-transfer and proton-transfer steps would be slower
2ϩ
ؒ
than the initial electron-transfer rate (k ). The maximum k
2
ϩ 29
et
et
0
value is evaluated from the ∆G value by eqn. (3), where Z is
et
11
Ϫ1 Ϫ1 40
the frequency factor taken as 1 × 10
Boltzmann constant.
M
s , and k is the
B
hyperfine splitting (hfs) values of two sets of methyl protons
4.86 and 3.35 G). As in the case of 1 , we assigned those hfs
ؒ
(
values as shown in Table 1 based on the calculated spin density
of Mg –1 by the ADF method (see Experimental section).
0
ket = Zexp(Ϫ∆G /k T )
(3)
2ϩ
ؒ
et
B
It is interesting to note that the spin density at C(8) of
0
Fig. 4 shows a plot of log kHT versus ∆G et, calculated by
2ϩ
ؒ
Mg –1 (ρ = 0.094) calculated using the ADF method is larger
than that at C(5) (ρ = 0.038) (see Supplementary Fig. S(1b)†),
while a relatively large amount of the spin density is accum-
eqn. (3) (denoted by the ET line). The k values of both the
H–DPPH and 1H–G systems (black circles) are signifi-
cantly above the ET line. The kHT value of the 1H–DPPH
system as well as that of the 1H–G system, which is much
larger than the corresponding ket value, indicates that the
hydrogen transfer proceeds via a direct one-step hydrogen trans-
fer rather than via electron transfer. In such a case, no effect of
HT
ؒ
ؒ
1
ؒ
ؒ
ulated at the C(5) and C(7) positions in 1 (Fig. S(1a)). The
ؒ
2
ϩ
ؒ
ؒ
same EPR spectrum of Mg –1 was obtained for the 1H–G –
2ϩ
2ϩ
ؒ
ؒ
Mg system. No interaction between Mg and DPPH or G
has been detected in the electronic spectra as well as in the
g values and hyperfine splitting constants of the EPR spectra
2ϩ
Mg on the kHT values should be observed, as is confirmed
ؒ
ؒ
2ϩ
of DPPH or G in the presence of Mg . No change in the
experimentally.
2ϩ
absorption spectra was observed either upon addition of Mg
On the other hand, the hydrogen transfer from an NADH
analogue, 10-methyl-9,10-dihydroacridine (AcrH ) (E
.81 V vs. SCE) to DPPH has been reported to proceed
via electron transfer from AcrH to DPPH , which is acceler-
to 1H.
0
ox
=
2
41
ؒ
0
Effects of magnesium ion on the rate of hydrogen transfer
ؒ
2
2ϩ
2ϩ
No effect of Mg on the kHT values of the hydrogen-transfer
ated by the presence of Mg , followed by proton transfer from
ؒ
ؒ
ؒ
ϩ
Ϫ
ؒ
reaction of 1H was observed in the case of DPPH or G used
as a hydrogen abstracting agent (see Supplementary Fig. S(2)†).
Thus, there may be no contribution of electron transfer from
AcrH2 to DPPH to yield the acridinyl radical (AcrH ) and
28
ؒ
DPPH2. The resulting AcrH is a much stronger reductant
0
ox
than AcrH , judging from the negative oxidation potential (E
2
ؒ
ؒ
28
41
1
H to DPPH or G in the hydrogen-transfer reaction, which
= Ϫ 0.43 V) as compared to that of AcrH (0.81 V), and
2
28
ؒ
may thereby proceed via a one-step hydrogen-transfer process.
thereby AcrH can readily transfer an electron to another
ؒ
ؒ
ؒ
ϩ
28
If the hydrogen transfer from 1H to DPPH or G involves an
electron-transfer process as the rate-determining step, the rate
of hydrogen transfer would be accelerated by the presence of
DPPH molecule to yield AcrH (Scheme 2). In such a case,
the kHT value (white circle in Fig. 4), which is much smaller than
the corresponding maximum k value, indicates that the hydro-
gen transfer proceeds via electron transfer followed by proton
transfer.
et
2ϩ
Mg which is known to accelerate the electron transfer to
ؒ
ؒ
28
DPPH and G .
Judging from the one-electron oxidation potential of 1H
In conclusion, the phenoxyl radical of the vitamin E
analogue 1H generated by hydrogen atom transfer from
0
(
E
vs. SCE = 0.77 V) which is higher than the one-electron
ox
ؒ
0
ؒ
ؒ
ؒ
2ϩ
reduction potential of DPPH (E
vs. SCE = 0.18 V) or G
1H to DPPH or G is significantly stabilized by Mg by
2ϩ
red
0
red
ؒ
(
E
vs. SCE = 0.05 V), the free energy change of electron
complexation of 1 with Mg as shown in Scheme 3.
ؒ
ؒ
0
2ϩ
transfer from 1H to DPPH or G is positive [∆G et(in eV) =
No effect of Mg on the hydrogen transfer rate from
0
0
ؒ
ؒ
e(E
Ϫ E red) > 0, where e is the elementary charge], and
1H to DPPH or G indicates that the hydrogen-transfer
ox
ؒ
ؒ
thereby the electron-transfer step is endergonic. In such a case,
the overall rate of hydrogen transfer (kHT) which consists of
reaction from 1H to DPPH or G proceeds via a one-step
hydrogen-transfer process rather than via electron transfer.
J. Chem. Soc., Perkin Trans. 2, 2002, 1520–1524
1523

View Article Online
W. A. Skinner and P. Alaupovic, J. Org. Chem., 1963, 28, 2854.
0 H. Meerwein, Angew. Chem., 1955, 67, 374.
1 K. Dimroth, W. Umbach and H. Thomas, Chem. Ber., 1967, 100,
32.
9
1
1
1
1
1
2 P. D. Boyer, J. Am. Chem. Soc., 1951, 73, 733.
3 W. Durckheimer and L. A. Cohen, J. Am. Chem. Soc., 1964, 86,
4
388.
1
4 C. Martius and H. Eilingsfeld, Liebigs Ann. Chem., 1957, 607,
59.
5 W. John, E. Dietzel and W. Emte, Z. Physiol. Chem., 1939, 257,
73.
1
1
1
1
1
6 W. A. Skinner and R. M. Parkhurst, J. Org. Chem., 1966, 31, 1248.
7 J. L. G. Nilsson, J. O. Branstad and H. Sievertsson, Acta Pharm.
Suec., 1968, 5, 509.
1
1
2
2
2
8 D. R. Nelan and C. D. Robeson, J. Am. Chem. Soc., 1962, 84,
2
963.
9 M. Jujimaki, K. Kanamaru, T. Kurata and O. Igarashi, Agric. Biol.
Chem., 1970, 34, 1781.
0 V. L. Frampton, W. A. Skinner, P. Cambour and P. S. Bailey, J. Am.
Chem. Soc., 1960, 82, 4632.
1 F. M. Dean, K. B. Hindley, L. E. Houghton and M. L. Robinson,
J. Chem. Soc., Perkin Trans. 1, 1976, 600.
2 S. Fukuzumi, in Advances in Electron Transfer Chemistry, ed.
P. S. Mariano, JAI Press, Greenwich, 1992, vol. 2, pp. 67–175; and
refs. cited therein.
Scheme 2
2
3 (a) D. Mauzerall and F. H. Westheimer, J. Am. Chem. Soc., 1955,
7
7, 2261; (b) R. H. Abeles, R. F. Hutton and F. H. Westheimer,
J. Am. Chem. Soc., 1957, 79, 712.
2
4 (a) E. M. Kosower, in Free Radicals in Biology, ed. W. A. Pryor,
Academic Press, New York, 1976, vol. II, ch. 1; (b) S. Fukuzumi and
T. Tanaka, in Photoinduced Electron Transfer, ed. M. A. Fox and
M. Chanon, Elsevier, Amsterdam, 1988, Part C, ch. 10.
2
2
2
5 U. Svanholm, K. Bachgaard and V. Parker, J. Am. Chem. Soc., 1974,
9
6, 2409.
6 G. W. Burton, T. Doba, E. J. Gabe, L. Hughes, F. L. Lee, L. Prasad
and K. U. Ingold, J. Am. Chem. Soc., 1985, 107, 7053.
7 (a) K. Mukai, K. Fukuda, K. Tajima and K. Ishizu, J. Org. Chem.,
1
988, 53, 430; (b) K. Mukai, Y. Kageyama, T. Ishida and
K. Fukuda, J. Org. Chem., 1989, 54, 552.
2
2
3
3
8 S. Fukuzumi, Y. Tokuda, Y. Chiba, L. Greci, P. Carloni and
E. Damiani, J. Chem. Soc., Chem. Commun., 1993, 1575.
9 S. Itoh, H. Kumei, S. Nagatomo, T. Kitagawa and S. Fukuzumi,
J. Am. Chem. Soc., 2001, 123, 2165.
0 K. Mann and K. K. Barnes, in Electrochemical Reactions in
Nonaqueous Systems, Marcel Dekker Inc., New York, 1990.
1 (a) E. J. Baerends, D. E. Ellis and P. Ros, Chem. Phys., 1973, 2, 41;
(b) G. te Velde and E. J. Baerends, J. Comput. Phys., 1992, 99, 84.
2 S. H. Vosko, L. Wilk and M. Nusair, Can. J. Phys., 1980, 58, 1200.
3 A. Becke, Phys. Rev. A, 1988, 38, 3098.
Scheme 3
3
3
Acknowledgements
34 (a) J. P. Perdew, Phys. Rev. B, 1986, 33, 8822; (b) J. P. Perdew, Phys.
Rev. B, 1986, 34, 7406.
This work was partially supported by a Grant-in-Aid for
Scientific Research Priority Area (No. 11228205) from
the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
3
5 L. Versluis and T. Ziegler, J. Chem. Phys., 1988, 88, 322.
36 V. W. Bowry and K. U. Ingold, J. Org. Chem., 1995, 60, 5456.
37 For the EPR spectrum of the phenoxyl radical derived from α-
tocopherol and its analogues, see (a) R. J. Singh, S. P. A. Goss,
J. Joseph and B. Kalyanaraman, Proc. Natl. Acad. Sci. USA, 1998,
9
5, 12912; (b) B. Kalyanaraman, V. M. Darley-Usmar, J. Wood,
J. Joseph and S. Parthasarathy, J. Biol. Chem., 1992, 267, 6789;
c) B. Kalyanaraman, W. E. Antholine and S. Parthasarathy,
Biochim. Biophys. Acta, 1990, 1035, 286; (d ) G. W. Burton, T. Doba,
E. J. Gabe, L. Hughes, F. L. Lee, L. Prasad and K. U. Ingold, J. Am.
Chem. Soc., 1985, 107, 7053; (e) J. Tsuchiya, E. Niki and Y. Kamiya,
Bull. Chem. Soc. Jpn., 1983, 56, 229; ( f ) W. Boguth and
H. Niemann, Biochim. Biophys. Acta, 1971, 248, 121.
References
(
1
L. J. Machlin, in Hand Book of Vitamins, ed. L. J. Machlin, Marchel
Dekker, New York, 2nd edn., 1991, pp. 99–144.
2
3
4
C. K. Chow, Free Radical Biol. Med., 1991, 11, 215.
G. W. Burton and K. U. Ingold, Acc. Chem. Res., 1986, 19, 194.
C. Suarna, D. C. Craig, K. J. Cross and P. T. Southwell-Keely, J. Org.
Chem., 1988, 53, 1281.
38 L. Valgimigli, J. T. Banks, K. U. Ingold and J. Lusztyk, J. Am. Chem.
Soc., 1995, 117, 9966.
5
6
7
8
M. Matsuo, S. Matsumoto and T. Ozawa, Org. Magn. Reson., 1983,
ؒ
2
1, 261.
T. Doba, G. W. Burton and K. U. Ingold, J. Am. Chem. Soc., 1983,
05, 6505.
39 The second-order decomposition rate constant for α-TO in
3
Ϫ1 Ϫ1
chlorobenzene at 296 K is reported as 3.9 × 10 M
s . See ref. 36
1
and refs cited therein.
G. W. Burton, T. Doba, E. Gaba, L. Hughes, F. L. Lee, L. Prasad
and K. U. Ingold, J. Am. Chem. Soc., 1985, 107, 7053.
40 (a) R. A. Marcus, Annu. Rev. Phys. Chem., 1964, 15, 155; (b)
R. A. Marcus, Angew. Chem., Int. Ed. Engl., 1993, 32, 1111.
41 S. Fukuzumi, Y. Tokuda, T. Kitano, T. Okamoto and J. Otera,
J. Am. Chem. Soc., 1993, 115, 8960.
S. Urano, S. Yamanoi, Y. Hattori and M. Matsuo, Lipids, 1977, 12,
1
05.
1
524
J. Chem. Soc., Perkin Trans. 2, 2002, 1520–1524