Unexpected Superoxide Dismutase Antioxidant Activity of Ferric Chloride in Acetonitrile

Article abstract of DOI:10.1021/jo034908u

The azobis(isobutyronitrile)-initiated autoxidation of γ-terpinene in acetonitrile at 50 °C yields onlyp-cymene and hydrogen peroxide (1:1) in a chain reaction carried by the hydroperoxyl radical, HOO^. (Foti, M. C.; Ingold, K. U. J. Agric. Food Chem. 2003, 51, 2758-2765). This reaction is retarded by very low (μM) concentrations of FeCl₃ and CuCl ₂. The kinetics of the FeCl₃-inhibited autoxidation are consistent with chain-termination via the following: Fe³⁺ + HOO ^. ? [Fe^IV-OOH]³⁺ and [Fe ^IV-OOH]³⁺ + HOO^. → Fe³⁺ + H₂O₂ + O₂. Thus, FeCl₃ in acetonitrile can be regarded as a very effective (and very simple) superoxide dismutase. The kinetics of the CuCl₂-inhibited autoxidation indicate that chain transfer occurs and becomes more and more important as the reaction proceeds, i.e., the inhibition is replaced by autocatalysis. These kinetics are consistent with-reduction of Cu²⁺ to Cu⁺ by HOO ^. and then the reoxidation of Cu⁺ to Cu²⁺ by both HOO^. and the H₂O₂ product. The latter reaction yields HO^. radicals which continue the chain.

Full text of DOI:10.1021/jo034908u

where RCy is the measured (by UV)1 rate of formation of
Cy and e is the efficiency of cage escape of the initial
geminate pair of radicals produced by AIBN, reaction 2.
The experimental rate law was in good agreement with
eq 7, viz.,1
Un exp ected Su p er oxid e Dism u ta se
An tioxid a n t Activity of F er r ic Ch lor id e in
Aceton itr ile
Mario C. Foti*,† and K. U. Ingold‡
Istituto di Chimica Biomolecolare del CNR, Sez di Catania
Via del Santuario 110, I-95028 Valverde, Italy, and
National Research Council, 100 Sussex Drive, Ottawa, ON,
K1A 0R6, Canada
RCy/M s-1 ) {(4.4 ( 0.3) × 10-4}[AIBN]0.52(0.09
[TH]0.95(0.08 (8)
foti@issn.ct.cnr.it
Received J une 26, 2003
During this work (which was designed to reveal the
mechanism by which TH inhibited the autoxidation of
linoleic acid, LH),1 we made the surprising discovery that
low concentrations of ferric chloride or cupric chloride
retarded the autoxidation of TH in acetonitrile. Our sur-
prise was due to the fact that transition metal ions are
well-known accelerators of the autoxidation of organic
compounds, though in a few systems (generally involving
high concentrations of transition metal ions) inhibition
of the autoxidation is observed.2 We therefore report on
the FeCl3- and CuCl2-inhibited AIBN-initiated (1-15
mM) autoxidation of TH (10-160 mM) in acetonitrile at
50 °C, and deduce their most probable mechanisms of
action.
Abstr a ct: The azobis(isobutyronitrile)-initiated autoxida-
tion of γ-terpinene in acetonitrile at 50 °C yields only p-cy-
mene and hydrogen peroxide (1:1) in a chain reaction carried
by the hydroperoxyl radical, HOO• (Foti, M. C.; Ingold, K.
U. J . Agric. Food Chem. 2003, 51, 2758-2765). This reaction
is retarded by very low (µM) concentrations of FeCl3 and
CuCl2. The kinetics of the FeCl3-inhibited autoxidation are
consistent with chain-termination via the following: Fe3+
+ HOO• a [FeIV-OOH]3+ and [FeIV-OOH]3+ + HOO• f Fe3+
+ H2O2 + O2. Thus, FeCl3 in acetonitrile can be regarded
as a very effective (and very simple) superoxide dismutase.
The kinetics of the CuCl2-inhibited autoxidation indicate
that chain transfer occurs and becomes more and more im-
portant as the reaction proceeds, i.e., the inhibition is re-
placed by autocatalysis. These kinetics are consistent with-
reduction of Cu2+ to Cu+ by HOO• and then the reoxidation
of Cu+ to Cu2+ by both HOO• and the H2O2 product. The
latter reaction yields HO• radicals which continue the chain.
In the presence of the metal chlorides, Cy was again1
the sole organic product of reaction 1. The rate of Cy
formation was the same for oxygen-saturated as for air-
saturated solutions in the absence1 and presence of the
metal ions. However, the presence of low concentrations
(µM) of both FeCl3 and CuCl2 greatly retarded the oxi-
dation of TH, see Table 1 and Figure 1. With FeCl3 there
was an induction period followed by oxidation at an
almost steady rate (see Figure 1 inset, curve B) for which
the rate law was
We have recently shown that the azobis(isobutyroni-
trile) (AIBN)-initiated autoxidation of the monoterpene,
γ-terpinene (TH), yields p-cymene (Cy) as the only
organic product:1
RCy/M s-1 ) {(9.0 ( 0.5 ) × 10-7
}
The oxidation chains are initiated by the peroxyl radicals
produced by AIBN, reactions 2 and 3, and carried by the
hydroperoxyl radical,1 reactions 4-6.
[ΑIΒΝ]0.45(0.05
[FeCl3]0.45(0.05
[TH]0.93(0.05
(9)
The rate of Cy formation during the induction period was
very much lower than the steady rate described by eq 9,
too low, in fact, to determine the order in FeCl3. With
CuCl2, the induction period was short and the rate rather
quickly approached the uninhibited rate (Figure 1 inset,
curve C vs curve A). Rates measured 5 min after the
reactants had been placed in a UV cuvette in the
spectrophotometer preheated to 50 °C could be described
by eq 10. The behavior of the two chlorides differs in more
kd
e
AIBN
9
8 [R• + N2 + R•]cage
8 2e R•
(2)
(3)
∆
-N2
O2
TH
R
• 98 ROO• -ROOH8T•
T• + O2 f Cy + HOO•
HOO• + TH f H2O2 + T•
HOO• + HOO• f H2O2 + O2
(4)
(5)
(6)
RCy/M s-1 ) {(1.3 ( 0.2) × 10-9
}
[AIBN]0.36(0.07
[CuCl2]0.91(0.05
[TH]1.31(0.07
(10)
Kinetic analysis of the above reactions yields the equation
k5
(2k6)0.5
than their kinetic rate laws. Thus, at comparatively high
concentrations (g11 µM) copper chloride was able to
initiate TH (ca. 65 mM) autoxidation to Cy in the absence
RCy
)
× (2ekd)0.5× [AIBN]0.5 × [TH]1.0 (7)
of AIBN with a measurable (5 min) rate of 6.7 × 10-8
M
* Corresponding author.
† Istituto di Chimica Biomolecolare del CNR, Italy.
‡ National Research Council, Ottawa, Canada.
(1) Foti, M. C.; Ingold, K. U. J . Agric. Food Chem. 2003, 51, 2758-
s-1, whereas FeCl3 at this concentration did not induce
measurable oxidation.
2765.
Of particular relevance for the present work is a 1963
10.1021/jo034908u CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/24/2003
9162
J . Org. Chem. 2003, 68, 9162-9165

TABLE 1. AIBN (8 m M)-In itia ted Oxid a tion of 50 m M
TH in Aceton itr ile a t 50 °C: Tim es Requ ir ed to P r od u ce
2.5 m M Cy (5% Rea ction )a in th e Absen ce a n d P r esen ce
of F eCl3 or Cu Cl2
pseudohalide ions in the presence of iron or copper salts.
Kochi5 has shown that these reactions are extremely
rapid and it has been pointed out by Minisci and
Fontana6 that ferric and cupric halides are among the
most effective traps for alkyl radicals. Since the compet-
ing trapping by dioxygen, reaction 12, is diffusion-
controlled,7 at the concentrations of O2 and FeCl3 used
by Hammond et al.,3 reaction 11 does not compete with
reaction 12. Hammond et al.3 also found that the addition
[FeCl3]/µM
time/sb
[CuCl2]/µM
time/sb
0
800
1240
1575
2140
3110
3900
0
800
1210
1500
1920
2100
0.31
0.61
1.21
2.38
4.58
1.3
2.6
5.2
10.4
a
Evaluated spectrophotometrically at 273 nm from the quantity
R• + O2 f ROO•
(12)
b
of p-cymene formed in solution (see Text). Error (10 s.
of a small amount of the hydroperoxide derived from the
two substrates, i.e., cumene hydroperoxide or Tetralin
hydroperoxide, increased the induction periods to such
an extent that their end was not observed. In contrast,
the addition of tert-butyl hydroperoxide did not increase
the induction periods. Moreover, the autoxidation of cy-
clohexene was not inhibited by FeCl3 but was strongly
inhibited by the addition of FeCl3 and Tetralin hydro-
peroxide.3 These workers3 also confirmed an earlier
report8 that, in benzene, FeCl3 catalyzed the decomposi-
tion of cumene hydroperoxide to phenol and acetone,9
reaction 13.
FeCl3
PhCMe2OOH
8PhOH + Me2CO
(13)
It was also shown that this reaction was very fast in
chlorobenzene.3 Since an ortho-alkylated phenol would
be expected from the FeCl3-catalyzed decomposition of
Tetralin hydroperoxide, but no phenol could be fromed
from tert-butyl hydroperoxide or cyclohexene hydroper-
oxide, it was concluded3 that the inhibition of autoxida-
tion of the two alkylaromatic hydrocarbons by FeCl3 was
due to peroxyl radical trapping by the phenols11 gener-
ated from their hydroperoxides, i.e.,
F IGURE 1. AIBN (8 mM)-initiated autoxidation of TH (50 mM)
in acetonitrile at 50 °C in the presence of different con-
centrations of FeCl3 during the induction period (9), after the
induction period ([), and different concentrations of CuCl2 5 min
after the start of the reaction (2). The metal ion inhibited rates,
R
inh, are plotted relative to the rate in the absence of metals, R0.
Inset: Growth in the 273-nm absorbance, due to Cy formation, as
a function of time under the above experimental conditions in the
absence of metal ions (A), in the presence of 2.4 µM FeCl3 (B),
and in the presence of 5.2 µM CuCl2 (C).
report by Hammond et al.3 in which it is shown that
0.05-2 mM FeCl3 gave well-defined induction periods in
the AIBN-initiated autoxidation of cumene and Tetralin
in chlorobenzene at 70 °C.
The rates of these FeCl3-inhibited autoxidations were
independent of the oxygen partial pressure. As Hammond
et al.3 pointed out, this means that the actual chain-
breaking process must involve the peroxyl radicals and
not the carbon-centered radicals, all carbon-centered
radicals being trapped by dioxygen. That is, chain-
breaking was not due to the ligand transfer oxidation of
the carbon-centered radicals (eq 11, with MXn ) FeCl3),
a process first reported by Minisci4 for X ) halide and
ROO• + ArOH f ROOH + ArO•
(14)
(15)
ROO• + ArO• f nonradical products
In principle, an analogous mechanism could be invoked
to explain the FeCl3-inhibited autoxidation of TH.12 Such
an explanation would require the Cy product to be oxi-
dized to p-methylcumene hydroperoxide, which is then
converted to p-cresol. However, oxidation of Cy during
the early stages of the reaction can be ruled out both on
kinetic grounds and by experiment. In the early stages
of TH oxidation not only is [Cy] , [TH]13 but also the
rate constants for hydrogen atom abstraction from cumene
(4) Minisci, F. Angew. Chem. 1958, 70, 599.
(5) Kochi, J . K. In Free Radicals; Kochi, J . K., Ed.; Wiley: New York,
1973; Chapter 11.
R• + MXn f RX + MXn-1
(11)
(6) Minisci, F.; Fontana, F. Tetrahedron Lett. 1994, 35, 1427-1430.
See also: Ingold, K. U.; MacFaul, P. A. In Biomimetic Oxidation
Catalyzed by Transition Metal Complexes; Meunier, B., Ed.; Imperial
College Press: London, UK, 1999; Chapter 2.
(2) There are at least two books2a,b and some reviews2c-f which
discuss (in whole or in part) transition metal-catalyzed autoxidations
of organic liquids and include mention of some odd exception where
autoxidations are inhibited by metal ions. (a) Emanuel, N. M.; Denisov,
E. T.; Maizus, Z. K. Liquid-Phase Oxidation of Hydrocarbons; Plenum
Press: New York, 1967. (b) Sheldon, R. A.; Kochi, J . K. Metal-Catalyzed
Oxidations of Organic Compounds; Academic Press: New York, 1981.
(c) Ingold, K. U. Chem. Rev. 1961, 61, 563-589. (d) Ingold, K. U. In
Metal Catalysed Lipid Oxidation; Svenska Institutet fo¨r Konserver-
ingsforskning (SIK) Rapport, 1968, No. 240, pp 11-41. (e) Marcuse,
R.; Fredeiksson, P.-O. In Metal Catalysed Lipid Oxidation; SIK
Rapport, 1968, No. 240, pp 97-103. (f) Howard, J . A. In Peroxyl
Radicals; Alfassi, Z. B., Ed.; Wiley: New York, 1997; Chapter 10.
(3) Hammond, G. S.; Mahoney, L. R.; Nandi, U. S. J . Am. Chem.
Soc. 1963, 85, 737-741.
(7) Maillard, B.; Ingold, K. U.; Scaiano, J . C. J . Am. Chem. Soc. 1983,
105, 5095-5099.
(8) Kharasch, M. S.; Fono, A.; Nudenberg, W. J . Org. Chem. 1950,
15, 748-752.
(9) The cumene hydroperoxide/FeCl3 reaction has recently been put
to synthetic use.10
(10) Liguori, L.; Bjorsvik, H.-R.; Fontana, F.; Bosco, D.; Galimberti,
L.; Minisci, F. J . Org. Chem. 1999, 64, 8812-8815.
(11) Or a ferric phenoxide.3
(12) TH autoxidation was inhibited by 0.3-5 µM FeCl3, concentra-
tions well below the minimum concentration of 50 µM used by
Hammond et al.3 to inhibit the autoxidation of cumene and Tetralin.
J . Org. Chem, Vol. 68, No. 23, 2003 9163

radicals can complex reversibly with transition metal
ions.2,16 Inhibition resulting from complex formation
could, in principle, be due to a decrease in the rate
constant for chain propagation by the complexed HOO•
(reaction 5) or an increase in the rate constant for chain
termination (reaction 6). The latter appears the more
probable in view of the very low (µM) concentration of
FeCl3 and CuCl2 required to produce substantial inhibi-
tion of the autoxidation of TH (cf. inhibition of hydro-
carbon and lipid autoxidation by peroxyl radical trapping
phenols at µM concentrations).2a,c,f
With FeCl3, chain termination by reactions 16 and 17
(which ignore the ligands on the iron)17 yields the kinetic
rate law for inhibition of TH autoxidation given in eq 18,
which is in excellent agreement with experiment, eq 9.
F IGURE 2. Rates of the AIBN (8.3 mM)-initiated autoxidation
of TH (40 mM) in acetonitrile at 50 °C in the presence of different
concentrations of cumene hydroperoxide and FeCl3. Key: [,
[FeCl3] ) 0; 9, [FeCl3] ) 4.5 µM; 2, [FeCl3] ) 18 µM.
Fe3+ + HOO• a [FeIV-OOH]3+
(16)
(a model for Cy) and TH by peroxyl radicals strongly
favor the latter reaction, viz., at 50 °C k(ROO• + cumene)
[FeIV-OOH]3+ + HOO• f Fe 3+ + H2O2 + O2 (17)
) 0.7 M-1 s-1 14 and k4 (HOO• + TH) ) 2800 M-1 s-1 1
.
0.5
k-16
Experimentally, with 50 mM [TH], 8 mM [AIBN], and 1
µM FeCl3 in acetonitrile at 50 °C, the rate of autoxidation
was unaffected by the deliberate addition of 10 mM Cy
(which is about three times the amount produced in 30
min in the absence of FeCl3). Furthermore, the addition
of cumene hydroperoxide to AIBN-initiated autoxidations
of TH in acetonitrile increased the rates of FeCl3-inhibited
reactions, rather than producing a further decrease in
rate, see Figure 2.
[AIBN]0.5
[Fe3+ 0.5
RCy/M s-1 ) k5(2ekd)0.5
[TH]
(18)
(
)
k16k17
]
Equation 18 can be rewritten by putting kinh ) k16k17/
k-16, where kinh represents the effective inhibition rate
constant, i.e.,
RCy/M s-1
)
k5(2ekd)0.5
k5[TH]Ri0.5
(kinh[Fe3+])0.5
[AIBN]0.5
The inability of cumene hydroperoxide + FeCl3 to
inhibit autoxidation under our conditions was confirmed
by using linoleic acid, rather that TH, as the oxidizable
substrate. It was found that autoxidation was accelerated
by FeCl3 alone and was further accelerated, in a dose-
dependent manner, by the addition of cumene hydro-
peroxide (see Supporting Information, Figure S1). The
accelerating effect of cumene hydroperoxide on the rates
of the FeCl3-modulated, AIBN-initiated autoxidation of
TH and linoleic acid in acetonitrile at 50 °C contrasts
with Hammond’s3 finding that the AIBN-initiated au-
toxidation of cyclohexene in chlorobenzene at 70 °C is
strongly inhibited by FeCl3 plus Tetralin hydroperoxide,
though it is not inhibited by FeCl3 alone. This difference
must be attributed to a solvent effect with the rate of
the FeCl3-catalyzed conversion of alkylaromatic hydro-
peroxides to phenols being much faster in chlorobenzene
than in acetonitrile. In this connection, it is interesting
to note that in the first publication on reaction 13,
Kharasch et al.8 reported that this reaction was fast in
benzene (where the FeCl3 is a strong Lewis acid) and that
the reaction did not occur in alcohol (where the FeCl3 is
a weak Lewis acid).
[TH]
)
(19)
[Fe3+ 0.5
]
0.5
kinh
where Ri ) 2ekd[AIBN] is the rate of chain initiation by
AIBN.18 Thus, ferric chloride catalytically and effectively
traps the chain-carrying hydroperoxyl, the conjugate acid
of the superoxide radical anion.17 Ferric chloride in
acetonitrile acts, therefore, as a superoxide dismutase
(SOD). This contrasts with the situation in water where
iron (aquo-iron) is not an effective SOD.20,21
With CuCl2, the rate law (determined after 5 min of
reaction), eq 10, has an order in TH greater than 1.0.
This indicates that inhibition is accompanied by a chain-
transfer step. Termination via reactions 20 and 21,
together with chain transfer (presumably mediated by
HO• radicals) via reaction 22, appears most plausible.22
Cu2+ + HOO• f Cu+ + O2 + H+
(20)
(21)
+
H
Cu+ + HOO• 8Cu2+ + H2O2
O2
Cu+ + H2O2 + TH
9
8Cu2+ + HO- + H2O + Cy +
HOO• (22)
Having eliminated two potential explanations for
inhibition of AIBN-initiated autoxidation of TH by FeCl3
and CuCl2, viz. (i) trapping of the T• radical (no oxygen
pressure dependence) and (ii) trapping of the chain
carrying hydroperoxyl radical1 by p-cresol formed in situ,
we are forced to conclude that inhibition is due to direct
reactions of the metal ions with the HOO• radical. There
is, in fact, a wealth of evidence indicating that peroxyl
Applying the usual steady-state approximation to the
radicals and Cu+ yields the rate expression25
(15) Howard, J . A.; Ingold, K. U. Can. J . Chem. 1967, 45, 793-802.
(16) Goldstein, S.; Meyerstein, D. Acc. Chem. Res. 1999, 32, 547-
550.
(17) In addition, the following discussions deal only with reaction
of the HOO• radical. We used “dry” acetonitrile in our experiments,
but cannot rule out contributions to the overall chemistry from its
conjugate base, superoxide. We also note that TH is not converted in
measurable yield into an epoxide under our experimental conditions
although FeCl3/H2O2 in dry acetonitrile is an epoxidation catalyst with
1,4-cyclohexadiene yielding 5% epoxide and 95% benzene, see: Sug-
imoto, H.; Sawyer, D. T. J . Org. Chem. 1985, 50, 1784-1786.
(13) Due to the spontaneous oxidation of TH, p-cymene is usually
present in mM concentrations even in distilled, neat TH.
(14) Based on a measured rate constant of 0.18 M-1 s-1 at 30 °C15
and an assumed Arrhenius preexponential factor of 108.5 M-1 s-1
.
9164 J . Org. Chem., Vol. 68, No. 23, 2003

Fe3+aq + HOO• f Fe2+ + O2 + H+
consistent with a
(26)
RCy ) k5[TH]
Rik21 + {(Rik21)2 + 8Rik20k21k22[TH][Cu2+][H2O2]}0.5
is slow with k26 < 103 M-1 s-1 21
,
prolonged lifetime for the initial [FeIV-OOH]3+ complex
(reaction 16), which permits the subsequent chain-ending
reaction 17 with a second HOO• radical. Moreover, the
fast reduction of Cu2+ to Cu+ by HOO• will, as the H2O2
concentration builds up, be followed by chain transfer,
4k20k21[Cu2+
]
(
)
(23)
Equation 23 is consistent with the autoacceleration ob-
served in the CuCl2-inhibited, AIBN-initiated oxidation
of TH in acetonitrile (see Figure 1 inset, curve C). At the
beginning of the reaction when there is no H2O2 present,
eq 23 simplifies to eq 24, while later when the H2O2 con-
centration has become significant, it simplifies to eq 25.
reaction 22, induced by the rather fast reaction 27 (k27
)
4.7 × 103 M-1 s-1).21
Cu+ + H2O2 f Cu2+ + HO- + HO•
(27)
aq
If any Fe2+ is actually formed by unimolecular decom-
position of [FeIV-OOH]3+ (to Fe2+, O2, and H+) it is roughly
k5[TH]Ri
2k20[Cu2+
k5[TH]1.5Ri0.5k220.5[H2O2]0.5
RCy
)
(24)
(25)
]
2 orders of magnitude less reactive than Cu+ in convert-
28,29
ing H2O2 into HO• radicals (k28 ≈ 50 M-1 s-1
)
RCy
)
(2k20k21[Cu2+])0.5
Fe 2+ + H2O2 f Fe3+ + HO- + HO•
(28)
aq
Thus, as the reaction progresses the order in [TH]
increases from 1.0 toward 1.5, the order in Ri decreases
from 1.0 toward 0.5, and the order in [CuCl2] changes
from -1.0 toward -0.5. The failure of theory to exactly
match eq 10 (for which rates were measured at a single
5-min time point rather than at equal [H2O2], i.e., equal
TH to Cy conversion) is hardly surprising.
Unlike FeCl3, CuCl2 is not a SOD in the AIBN/TH/
acetonitrile system. The CuCl2 only functions as an
antioxidant at the start of the reaction where [H2O2] is
low because the reduction of CuII to CuI in reaction 20
allows chain-transfer via reaction 22 to compete with the
chain-terminating reoxidation of CuI to CuII by the HOO•
radical, reaction 21. This difference in the behavior of
the two metals is concordant with the reported rate
constants for relevant reaction in water. Thus, k20 (for
Exp er im en ta l Section
Acetonitrile and all the other chemicals were of the purest
grade commercially available and were used as received except
for AIBN, which was recrystallized from methanol and stored
at -20 °C. The kinetics were monitored on a Perkin-Elmer
Lambda 25 UV/VIS double ray spectrometer; the GC-MS analy-
ses were done on a Hewlett-Packard 5890 interfaced to a
Hewlett-Packard 5971A Mass Selective Detector (DB-5 capillary
column, 30 m × 0.25 mm, film thickness 0.25 µm).
P er oxid a tion of γ-Ter p in en e in th e Absen ce a n d P r es-
en ce of F eCl3 or Cu Cl2. Solutions of γ-terpinene (final con-
centration 10-160 mM) and AIBN (final concentration 1-15
mM) in acetonitrile were mixed 1:1 (v/v) in a UV-cuvette (optical
path, 1.0 cm) saturated with air or oxygen at 1 atm and quickly
heated to 50 °C. Thereafter, the cell compartment was main-
tained at 50 °C and the absorbance at 273 nm (corresponding
to a maximum p-cymene absorbance) was monitored over time
as previously described.1 Excellent straight lines (R2 ) 0.97-
0.99) of absorbance vs time were usually obtained whose slopes
(divided by 390 M-1 cm-1) gave the rate of reaction, d[Cy]/dt in
M s-1. In the case of the metal-inhibited oxidations, 10-80 µL
aliquots of a concentrated solution of FeCl3 (final concentration
0.3-5 µM) or CuCl2 (final concentration 1-8 µM) in acetonitrile
were added along with the other reactants before saturating the
solutions with O2 or air. The reaction orders for AIBN, γ-ter-
pinene, FeCl3, or CuCl2 were obtained by changing the concen-
tration of the pertinent species while keeping the others
constant. Acetonitrile was employed in these oxidations to
solubilize the two metal chlorides which were employed at
concentrations sufficiently low that their own UV absorptions
did not interfere with measurements of Cy formation.
CuIIaq) ) 1 × 109 M-1 s-1 21
,
which implies that the
expected [CuI-OOH]2+ intermediate is much too short-
lived to enter into a bimolecular, chain-terminating step
with a second HOO• radical (analogous to reaction 17).
In contrast, the overall reaction
1
(18) From the values in acetonitrile at 50 °C of k4 ) 2800 M-1 s-1
.
19
2ekd ) 2.0 × 10-6 s-1
,
and the numerical factor of the experimental
eq 9, it is possible to calculate that FeCl3 inhibits reaction 1 with a
kinh ) 1.9 × 1013 M-2 s-1
.
(19) Foti, M. C.; Ruberto, G. J . Agric. Food Chem. 2001, 49, 342-
348.
(20) For an excellent review of models of superoxide dismutases see
ref 21. Effective model SODs generally contain Cu, Fe, or Mn chelated
by a multidentate ligand, with the Mn complexes generally being the
most active.
Note Ad d ed a fter ASAP P ostin g. The formal oxida-
tion number of iron in the complex [FeIV-OOH]3+ in eqs
16 and 17 and the TOC graphic was incorrect in the
version posted ASAP October 24, 2003; the corrected
version was posted October 28, 2003.
(21) Cabelli, D. E.; Riley, D.; Rodriguez, J . A.; Valentine, J . S.; Zhu,
H. In Biomimetic Oxidations Catalyzed by Transition Metal Complexes;
Meunier, B., Ed.; Imperial College, Press: London, UK. 1999; Chapter
10.
(22) Hydrogen atom abstraction by the HO• radical will partition
approximately 80% in favor of the 50 mM TH (for which a reasonable
Su p p or tin g In for m a tion Ava ila ble: Effect of FeCl3 on
the rates of the AIBN-initiated autoxidation of linoleic acid
(Figure S1). This material is available free of charge via the
Internet at http://pubs.acs.org.
model is 1,4-cyclohexadiene, k ) 7.7 × 109 M-1 s-1
)
23 and approximately
20% in favor of the ca. 19 M acetonitrile (k ) 5.5 × 106 M-1 s-1).24 Of
course, the 20% of radicals formed by H-atom abstraction from the
acetonitrile will rapidly add oxygen and the resultant peroxyl will
abstract from TH to yield T•.
J O034908U
(23) Michael, B. D.; Hart, E. J . J . Phys. Chem. 1970, 74, 2878-2884.
(24) Draganic, I.; Draganic, Z.; Petkovic, Lj.; Nikolic, A, J . Am. Chem.
Soc. 1973, 95, 7193-7199.
(26) Mahoney, L. R.; Ferris, F. C. J . Am. Chem. Soc. 1963, 85, 2345-
2346.
(27) Howard, J . A.; Ingold, K. U. Can. J . Chem. 1964, 42, 2324-
2332.
(28) Barb, W. G.; Baxendale, J . H.; George, P.; Hargrave, K. R.
Trans. Faraday Soc. 1951, 47, 462-500.
(29) Hardwick, T. J . Can. J . Chem. 1957, 35, 428-436.
(25) Analogous kinetics have been observed in the phenol-inhibited,
AIBN-initiated autoxidation of Tetralin.26,27 Termination involves
reactions 14 and 15 (Ar ) Ph) and chain transfer the following
reaction: PhO• + RH f PhOH + R•. Kinetic analysis with some
simplifying assumptions26,27 yields an inhibited oxidation rate propor-
tional to [Tetralin]1.5[AIBN]0.5/[PhOH]0.5
.
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