Redox properties of a mononuclear copper(II)-superoxide complex

Article abstract of DOI:10.1021/ic401261z

Redox properties of a mononuclear copper(II) superoxide complex, (L)Cu ^II-OO^?, supported by a tridentate ligand (L = 1-(2-phenethyl)-5-[2-(2-pyridyl)ethyl]-1,5-diazacyclooctane) have been examined as a model compound of the putative reactive intermediate of peptidylglycine α-hydroxylating monooxygenase (PHM) and dopamine β-monooxygenase (DβM) (Kunishita et al. J. Am. Chem. Soc. 2009, 131, 2788-2789; Inorg. Chem. 2012, 51, 9465-9480). On the basis of the reactivity toward a series of one-electron reductants, the reduction potential of (L)Cu^II-OO ^? was estimated to be 0.19 ± 0.07 V vs SCE in acetone at 298 K (cf. Tahsini et al. Chem. - Eur. J. 2012, 18, 1084-1093). In the reaction of TEMPO-H (2,2,6,6-tetramethylpiperidine-N-hydroxide), a simple HAT (hydrogen atom transfer) reaction took place to give the corresponding hydroperoxide complex LCu^II-OOH, whereas the reaction with phenol derivatives (^XArOH) gave the corresponding phenolate adducts, LCu ^II-O^XAr, presumably via an acid-base reaction between the superoxide ligand and the phenols. The reaction of (L)Cu^II-OO ^? with a series of triphenylphosphine derivatives gave the corresponding triphenylphosphine oxides via an electrophilic ionic substitution mechanism with a Hammett ρ value as -4.3, whereas the reaction with thioanisole (sulfide) only gave a copper(I) complex. These reactivities of (L)Cu^II-OO^? are different from those of a similar end-on superoxide copper(II) complex supported by a tetradentate TMG ₃tren ligand (1,1,1-Tris{2-[N²-(1,1,3,3- tetramethylguanidino)]ethyl}amine (Maiti et al. Angew. Chem., Int. Ed. 2008, 47, 82-85).

Full text of DOI:10.1021/ic401261z

Article
pubs.acs.org/IC
Redox Properties of a Mononuclear Copper(II)-Superoxide Complex
Tetsuro Tano,† Yuri Okubo,† Atsushi Kunishita,† Minoru Kubo,‡ Hideki Sugimoto,† Nobutaka Fujieda,†
Takashi Ogura,‡ and Shinobu Itoh*,†
†Department of Material and Life Science, Division of Advanced Science and Biotechnology, Graduate School of Engineering, Osaka
University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan
‡Research Institute of Picobiology, Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto, Kamigori-cho, Ako-gun,
Hyogo 678-1297, Japan
S
* Supporting Information
ABSTRACT: Redox properties of a mononuclear copper(II)
superoxide complex, (L)CuII−OO•, supported by a tridentate
ligand (L = 1-(2-phenethyl)-5-[2-(2-pyridyl)ethyl]-1,5-diaza-
cyclooctane) have been examined as a model compound of the
putative reactive intermediate of peptidylglycine α-hydroxylat-
ing monooxygenase (PHM) and dopamine β-monooxygenase
(DβM) (Kunishita et al. J. Am. Chem. Soc. 2009, 131, 2788−
2789; Inorg. Chem. 2012, 51, 9465−9480). On the basis of the
reactivity toward a series of one-electron reductants, the
reduction potential of (L)CuII−OO• was estimated to be 0.19
0.07 V vs SCE in acetone at 298 K (cf. Tahsini et al.
Chem.Eur. J. 2012, 18, 1084−1093). In the reaction of TEMPO-H (2,2,6,6-tetramethylpiperidine-N-hydroxide), a simple HAT
(hydrogen atom transfer) reaction took place to give the corresponding hydroperoxide complex LCuII−OOH, whereas the
reaction with phenol derivatives (XArOH) gave the corresponding phenolate adducts, LCuII−OXAr, presumably via an acid−base
reaction between the superoxide ligand and the phenols. The reaction of (L)CuII−OO• with a series of triphenylphosphine
derivatives gave the corresponding triphenylphosphine oxides via an electrophilic ionic substitution mechanism with a Hammett
ρ value as −4.3, whereas the reaction with thioanisole (sulfide) only gave a copper(I) complex. These reactivities of (L)CuII−
OO• are different from those of a similar end-on superoxide copper(II) complex supported by a tetradentate TMG3tren ligand
(1,1,1-Tris{2-[N2-(1,1,3,3-tetramethylguanidino)]ethyl}amine (Maiti et al. Angew. Chem., Int. Ed. 2008, 47, 82−85).
can be generated by the one-electron reduction of A and
subsequent protonation of a copper(II)-peroxide complex B or
direct hydrogen atom transfer to A from a substrate.
Furthermore, O−O bond homolysis of the hydroperoxide
complex C may occur to provide a mononuclear copper(II)-
oxyl radical species D (Scheme 1). In synthetic modeling
systems, however, copper(II)-superoxide complex A tends to
react with another molecule of copper(I) starting material to
give a dinuclear copper(II)-peroxide complex (not shown in
INTRODUCTION
■
Mononuclear copper active-oxygen species are the important
reactive intermediates in biological oxygenation reactions.1−12
Copper monooxygenases such as peptidylglycine α-hydroxylat-
ing monooxygenase (PHM), dopamine β-monooxygenase
(DβM), and tyramine β-monooxygenase (TβM) have been
demonstrated to catalyze aliphatic C−H bond hydroxylation of
their respective substrates (dopamine, peptide hormones, and
tyramine, respectively) using molecular oxygen (O2) at a
mononuclear copper active site.1,13−16 It has also been
suggested that bacterial depolymerization of polysaccharides
is initiated by a class of copper oxygenases (GH61 and
CBM33), in which O2-activation is taking place at a
mononuclear copper reaction center for the substrate oxygen-
ation.17−21 So far, the series of mononuclear copper active-
oxygen species such as superoxide (A), peroxide (B),
hydroperoxide (C), and oxyl radical (D) complexes have
been proposed as the key reactive intermediate for the direct
aliphatic C−H bond activation from both enzymatic and
computational studies.1,4,13,15,22−31
Scheme 1
In principle, the reaction of a mononuclear copper(I)
complex and O2 gives a mononuclear copper(II)-superoxide
complex A, from which a copper(II)-hydroperoxide complex C
Received: May 21, 2013
Published: September 5, 2013
© 2013 American Chemical Society
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Chart 1
precipitated by standing in the mixture for several minutes. The
supernatant was then removed by decantation, and the remained blue
solid was washed with n-hexane three times and dried to give 2OAc in
Scheme 1), making it difficult to isolate and characterize the
mononuclear copper active-oxygen complexes in the reaction of
copper(I) complexes and O2.2,3,12 Nonetheless, a couple of
mononuclear copper(II) end-on superoxide complexes have
recently been characterized,32,33 and one of them, (TMG3tren)-
CuII−OO•, has been successfully isolated by using the
tetramethylguanidine derivative of tripodal tetradentate tren
ligand (tris(2-aminoethyl)amine) (Chart 1),34 providing
important insights into the structure and chemical properties
of the proposed reaction intermediate of the mononuclear
copper oxygenases.35−37 We have also studied the reactivity of
−
71%. FT-IR (KBr) 1610 and 1578 cm−1 (OAc−), 1083 cm−1 (BF4 );
HR-MS (FAB, pos) m/z = 445.1798, calcd for C23H32N3O2Cu =
445.1791; Anal. Calcd for [CuII(OAc)](BF4)·1.5H2O·0.1C6H14
(C23.6H36.4BCuF4N3O3.5): C, 49.86; H, 6.45; N, 7.39. Found: C,
49.65; H, 6.39; N, 7.13.
EPR Measurements. The EPR spectrum of the final reaction
mixture of copper(II) superoxide complex 2O and TEMPO-H were
2
recorded on a JEOL X-band spectrometer (JES-RE1XE) with an
attached variable temperature apparatus. The EPR spectrum was
measured in frozen acetone at 77 K. The magnitude of modulation was
chosen to optimize the resolution and the signal-to-noise (S/N) ratio
of the observed spectra under nonsaturating microwave conditions.
The g values and the hyperfine coupling constants were calibrated with
a Mn2+ marker.
Resonance Raman Spectrum. Resonance Raman scattering was
excited at 406.7 nm from Kr+ laser (Spectra Physics, BeamLok 2060).
Resonance Raman scattering was dispersed by a single polychromator
(Ritsu Oyo Kogaku, MC-100) and was detected by a liquid nitrogen
cooled CCD detector (Roper Scientific, LNCCD-1100-PB). The
resonance Raman measurements were carried out using a rotated
cylindrical cell thermostatted at −70 to −90 °C by flashing cold liquid
nitrogen gas.
the end-on superoxide copper(II) complex 2O generated by
2
using a tridentate ligand L (Chart 1) to demonstrate that 2O
2
can directly induce aliphatic hydroxylation at the benzylic
position of the ligand side arm, providing important insight into
the catalytic mechanism of PHM and DβM.38,39 In this study,
we have examined the redox properties of 2O toward several
2
types of external substrates to get further insights into the
intrinsic reactivity of the end-on superoxide copper(II) complex
and to see how the supporting ligand affects the reactivity of the
superoxide complexes. We have also tried to see the formation
of possible mononuclear copper active oxygen species such as
peroxide (one-electron reduced product B), hydroperoxide
(hydrogen atom adduct C), and oxyl radical (D) complexes,
which could be derived from 2O in the reactions with external
2
Kinetic Measurements. Kinetic measurements for the reactions of
copper(II) superoxide complex 2O with external substrates were
2
substrates (see Scheme 1).
performed using a Hewlett-Packard 8453 photo diode array
spectrophotometer with a Unisoku thermostatted cell holder designed
for low temperature measurements (USP-203, a desired temperature
can be fixed within 0.5 °C) in an appropriate solvent (3.0 mL) at a
low temperature. For the preparation of the copper(II) superoxide
complex 2O2, O2 gas was rapidly introduced to a solution of the
copper(I) complex [(L)CuI]PF6 in a UV cell (1.0 cm path length)
through a silicon rubber cap by using a gastight syringe, and the
EXPERIMENTAL SECTION
■
Materials and Methods. The reagents and the solvents used in
this study, except the ligands and the copper complexes, were
commercial products of the highest available purity and were further
purified by the standard methods, if necessary.40 The ligand 1-(2-
phenethyl)-5-[2-(2-pyridyl)ethyl]-1,5-diazacyclooctane (L) and its
copper(I) complex [(L)CuI]PF6 (1) were prepared according to the
reported procedures.38 FT-IR spectra were recorded on a Jasco FTIR-
4100, and UV−visible spectra were taken on a Hewlett-Packard 8453
photo diode array spectrophotometer. 1H NMR spectra were recorded
on a JEOL LMN−ECP300WB, a JEOL ECP400, a JEOL ECS400, or a
Varian UNITY INOVA 600 MHz spectrometer. ESI-MS (electrospray
ionization mass spectra) measurements were performed on a
PerSeptive Biosystems Mariner Biospectrometry workstation. Ele-
mental analyses were performed on a Perkin-Elmer or a Fisons
instruments EA1108 Elemental Analyzer.
increase of the absorption band due to 2O was monitored. Then, an
2
excess O2 was removed by flashing Ar gas through a needle for about 5
min, and the substrate was added to start the reaction. The reaction
was followed by monitoring the decrease in the ligand-to-metal charge
transfer (LMCT) absorption band due to 2O2. The pseudo-first-order
rate constants for the decay of 2O were determined from the plots of
2
ln(ΔA) vs time based on the time course of the absorption change at
λmax due to 2O2.
Quantification of H2O2. Amount of H2O2 was determined by
Synthesis. [CuII(L)(OAc)](BF4) (2OAc). Ligand L (20 mg, 62 μmol)
was treated with an equimolar amount of CuII(CH3COO)2·H2O (12
mg, 62 μmol) in CH2Cl2 (5.0 mL). After stirring the mixture for 5 min
at room temperature, NaBF4 (6.8 mg, 62 μmol) was added to the
solution. Insoluble material was then removed by filtration. Addition of
n-hexane (100 mL) to the filtrate gave a blue powder that was
iodometry as follows. A final reaction mixture of 2O and a substrate
2
was quenched by adding an acetone solution of HPF6 (2 equiv). Then,
the diluted acetone solution (1/10) was treated with an excess NaI.
−
The amount of I3 formed was then quantified using its visible
spectrum (λmax = 361 nm, ε = 2.5 × 104 M−1 cm−1).41
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RESULTS AND DISCUSSION
Table 1. One-Electron Oxidation Potential of the Reductants
and the Second-Order Rate Constants for the Reduction of
■
Electron-Transfer Reduction of 2O2. As shown in Scheme
2O in Acetone at −85 °C
2
1 in the Introduction, one-electron reduction of the copper(II)-
superoxide complex 2O may afford a copper(II)-peroxide
2
Me10Fc
Me8Fc
TMPD
0.12
9.4 0.06
Me2Fc
0.26
Fc
complex B. Thus, the reactions of 2O with a series of one-
2
a
E0ox/V vs SCE
k2/M−1 s−1
−0.08
−0.04
56 0.4
0.37
electron reductants were examined to search such a possibility.
Figure 1 shows a typical example of the spectral change for the
b
b
320
2
NR
NR
a
b
The data are taken from the literature.42 No reaction.
irreversible because of the thermal instability of the reduced
product; addition of an oxidant such as ferrocenium cation Fc+
to the final reaction mixture did not reproduce the original
superoxide complex 2O2. Thus, the estimated Ered value is not a
true reduction potential.
Reaction with TEMPO-H (Hydrogen-Atom Donor).
Figure 2 (left) shows a spectral change for the reaction of
2O with 2,2,6,6-tetramethylpiperidine-N-hydroxide (TEMPO-
2
H) under anaerobic conditions (excess O2 was removed by
flushing Ar gas before the reaction), where the absorption
bands due to 2O decrease to give new absorption bands at 375
2
nm (ε = 1650 M−1 cm−1) and 620 nm (309). The final
spectrum is similar to those of copper(II)-hydroperoxide
complexes that so far have been reported,43 suggesting the
formation of a similar type of copper(II)-hydroperoxide
complex 2OOH (Scheme 2), even though resonance Raman
data of sufficient quality has yet to be obtained; there is only a
very weak Raman band at 831 cm−1, which shifted to 788 cm−1,
Figure 1. UV−vis spectral change for the reaction of 2O (0.2 mM)
2
and decamethylferrocene (0.2 mM) in acetone at −85 °C. Inset:
Second-order plot based on the absorption change at 397 nm.
when the reaction was carried out with 18O-substituted 2O
2
reaction of 2O (0.2 mM) with an equimolar amount of
(see, Figure S4). The reaction obeyed first-order kinetics in the
presence of an excess amount of TEMPO-H (Figure 2 (left),
Inset), and a plot of the observed pseudofirst-order rate
constants against the concentration of TEMPO-H gave a
straight line passing through the origin, from which the second
rate constant was determined as k2 = 2.4 0.05 M−1 s−1 at −85
°C (Figure 2, right).
2
decamethylferrocene (Me10Fc) at −85 °C in acetone. The
LMCT band at 397 nm due to 2O gradually decreased with a
2
concomitant increase of the absorption band due to the
ferrocenium cation (Me10Fc+). The yield of Me10Fc+ was
estimated to be 88% based on the initial concentration of 2O
2
using the intensity of the absorption band due to Me10Fc+ itself
(ε = 8.0 × 102 M−1 cm−1 at λmax = 780 nm). This is consistent
with a one-electron reduction of the superoxide species. In fact,
nearly quantitative formation of H2O2 (81% based on 2O2, 92%
based on Me10Fc+ formed) was confirmed by iodometry as
shown in Supporting Information, Figure S1A, and quantitative
generation of a copper(II) complex was detected by the EPR
spectrum (Supporting Information, Figure S1B). However, all
our efforts to isolate the reduced product (type B in Scheme 1)
have been unsuccessful because of its thermal instability, and a
complicated mixture of products was obtained, when the
reaction mixture was warmed to room temperature.
The EPR spectrum of the final reaction mixture shown in
Supporting Information, Figure S5 exhibited the typical signal
due to TEMPO• free-radical (g = 2.004) (Supporting
Information, Figure S5B), which is overlapped with a EPR
signal of a copper(II) species (Supporting Information, Figure
S5A). The spin quantification by double integration of the
whole EPR signals confirms the existence of two S = 1/2
species corresponding to TEMPO• and copper(II)-hydro-
peroxide species 2OOH
.
2OOH was relatively stable at −85 °C, but gradually
decomposed at room temperature to give a copper(II) complex
having a weak d-d band at 640 nm (ε = 210 M−1 cm−1)
(Supporting Information, Figure S6). In addition, quantitative
formation of H2O2 (93% based on the copper complex) was
confirmed by iodometry after quenching the final reaction
mixture with HPF6 (Supporting Information, Figure S7). It
should be noted that no ligand hydroxylation product was
detected from the final reaction mixture by ESI-MS
(Supporting Information, Figure S8), and the original ligand
was recovered quantitatively by the ordinary workup treatment
(demetalation) of the final reaction mixture using NH4OH (aq)
(Scheme 3a). This result is in sharp contrast to the
(TMG3tren)CuII−OO• system, where a ligand hydroxylation
took place only after the reaction with hydrogen atom donor
such as TEMPO-H or phenols (Scheme 3b).36 The authors
concluded that (TMG3tren)CuII−OO• (type A in Scheme 1)
was not the direct oxidant, but that (TMG3tren)CuII−O• (type
D) generated by O−O bond homolysis of (TMG3tren)CuII−
The decay of 2O obeyed second-order kinetics in the
2
presence of the equimolar amount of Me10Fc, and the second-
order rate constant (k2) was obtained as 320 2 M−1 s−1 from
the slope of the linear line of the second-order plot shown in
the inset of Figure 1. The reduction of 2O also proceeded with
2
octamethylferrocene (Me8Fc) and N,N,N′N′-tetramethylphe-
nylenediamine (TMPD), and the second-order rate constants
were determined as 56 0.4 M−1 s−1 and 9.4 0.06 M−1 s−1,
respectively, as shown in Supporting Information, Figures S2
and S3, respectively (the data are listed in Table 1). On the
other hand, no reaction took place when weaker reductants
such as dimethylferrocene (Me2Fc) and ferrocene (Fc) were
employed under the same experimental conditions (Table 1).
On the basis of the one-electron oxidation potentials of TMPD
(Eox = 0.12 V vs SCE) and Me2Fc (Eox = 0.26 V vs SCE),42 the
one-electron reduction potential of 2O was estimated as Ered
=
2
(0.19 V 0.07) vs SCE. However, the reduction of 2O was
2
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Figure 2. Left: UV−vis spectral change for the reaction of 2O (0.2 mM) and TEMPO-H (4.0 mM) in acetone at −85 °C. Inset: Pseudo-first-order
plot based on the absorption change at 397 nm. Right: Plot of kobs against the substrate concentration for the reaction of 2O2.
2
(TMG3tren)CuII−OO• and phenols (ArOH) induced hydro-
Scheme 2
gen atom transfer to provide (TMG3tren)CuII−OOH and
phenoxyl radical species (ArO•), from which the ligand
hydroxylation product (Scheme 3b) and several phenol
oxidation/oxygenation products were produced.36 Thus, we
also investigated the reaction of 2O with phenol derivatives to
2
compare the reactivity between 2O and (TMG3tren)CuII−
2
OO•. Figure 3 shows a spectral change for the reaction of 2O
2
OOH (type C), generated by the reaction of A and the
hydrogen atom donor, might be the reactive intermediate that
induced the ligand methyl hydroxylation.36 On the other hand,
our results clearly indicated that the superoxide complex 2O
2
(Type A), but not the hydroperoxide complex 2OOH (type C),
directly participates in the aliphatic ligand hydroxylation
(Scheme 3a).38,39 Such a difference in reactivity between 2O
2
and (TMG3tren)CuII−OO• could be attributed in part to the
difference in the coordination number and geometry (four-
coordinate/tetrahedral vs five-coordinate/trigonal bipyramidal)
as well as to the difference in the kind of donor atoms
(alkylamine and pyridine nitrogen atoms vs imine (guanidine)
nitrogen atoms). It is interesting to note that the proposed
Figure 3. UV−vis spectral change for the reaction of 2O (0.2 mM)
2
geometry (distorted tetrahedral)38 and observed reactivity
with p-tert-butylphenol (180 mM) in acetone at −85 °C. Each
(direct C−H bond activation)38 of 2O are closer to those of
2
spectrum was taken at 500 s intervals. Inset: Plot of kobs against the
the putative reactive intermediate in the enzymes.44,45
substrate concentration.
Reaction with Phenol Derivatives. Karlin, Schindler,
Sundermeyer, and co-workers reported that the reaction of
Scheme 3
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with p-tert-butylphenol (tBuArOH) as a typical example, where
the LMCT bands due to 2O decrease obeying first-order
2
kinetics in the presence of an excess amount of tBuArOH.
A plot of the pseudo-first-order rate constants (kobs) against
the substrate concentration gave a straight line passing through
the origin, from which the second-order rate constant k2 was
determined to be (0.68 0.01) × 10−2 M−1 s−1 from the slope
(Figure 3, Inset). In this case, the spectrum of the final reaction
mixture exhibiting weak absorption bands at 530 nm (ε = 485
M−1 cm−1) and 725 nm (ε = 405 M−1 cm−1), which was
different from that of 2OOH (see, Figure 2) but identical to that
of the copper(II)-phenolate complex (2OAr(tBu)) prepared by
the reaction of a copper(II) complex [CuII(L)(OCOCH3)]+
(2OAc) and lithium p-tert-butylphenolate under the same
experimental conditions (Supporting Information, Figure
S9).46 Thus, the product was not the copper(II)-hydroperoxide
Figure 4. Eyring plot for the reaction of 2O (0.2 mM) with MeOArOH
in acetone.
2
complex 2OOH, but a copper(II)-phenolate complex 2OAr(tBu)
.
Furthermore, no phenol coupling dimer product was obtained,
when the final reaction mixture was quenched with HPF6 at the
low temperature (−85 °C).
A simple hydrogen atom transfer (HAT) mechanism from
the phenol substrate by the superoxide complex may be ruled
out, since the putative copper(II)-hydroperoxide complex 2OOH
was not detected during the course of the reaction, and no
phenoxyl radical coupling dimer product was obtained after the
reaction (vide ante).
The reactions of 2O with a series of p-substituted phenols
2
(XArOH; X = OPh, Me, H, F, Cl) were also examined under
the same experimental conditions to give the corresponding
copper(II)-phenolate complexes (2OAr(X)) (Supporting Infor-
mation, Figure S10−S15), and the second-order rate constants
k2 for the reactions were determined in the same manner as
(0.51 0.01) × 10−2 M−1 s−1, (0.22 0.01) × 10−2 M−1 s−1,
(0.37 0.3) × 10−2 M−1 s−1, (0.42 0.02) × 10−2 M−1 s−1,
(0.42 0.01) × 10−2 M−1 s−1, and (2.0 0.1) × 10−3 M−1 s−1,
respectively, at −85 °C (Supporting Information, Figure S10−
S15). When C6D5OD (fully deuterated phenol) was employed
instead of C6H5OH, there was an appreciable amount of kinetic
deuterium isotope effect (KIE = 2.2); kobs(H) = 9.2 × 10−4 s−1 vs
kobs(D) = 4.2 × 10−4 s−1 (Supporting Information, Figure S16).
Formation of the copper(II)-phenolate complexes suggests
that the reaction involves a simple acid−base reaction between
Reaction with Phosphine and Sulfide. The reaction of
2O with triphenylphosphine derivatives was studied to examine
2
the oxo-transfer ability of the superoxide complex. Figure 5
X
•−
the phenol substrate ArOH and the superoxide ligand (O2
)
in 2O to generate the copper(II)-phenolate complex, ArO-
X
2
CuII, and HO2 , the latter of which may rapidly dispropor-
•
X
tionate into (1/2)O2 and (1/2)H2O2 (Scheme 4, R = Ar).
This was confirmed by iodometric detection of H2O2 in a 49%
yield based on 2O (Supporting Information, Figure S17).
2
Scheme 4
Figure 5. UV−vis spectral change for the reaction of 2O (0.2 mM)
2
with P(ArMe)3 (4.0 mM) in acetone at −85 °C. Each spectrum was
taken at 200 s intervals. Inset: Plot of kobs against the substrate
concentration.
shows a spectrum change for the reaction of 2O with tris(4-
2
If the proton transfer from the phenol substrate to the
superoxide ligand occurs via a simple bimolecular reaction, the
rate constant k2 should increase as the pKa of phenols decreases
(as the acidity of phenols increases). Such a rate-dependence
on the pKa values was actually observed as shown in Supporting
Information, Figure S18, although the correlation is not so
good. In support of this mechasnim, addition of a stronger acid
methylphenyl)phosphine P(ArMe)3 as a typical example, where
the decrease of the LMCT bands due to 2O obeys first-order
2
kinetics in the presence of a large excess of the substrate.
A plot of the observed first-order rate constants against the
substrate concentration gave a straight line passing through the
origin, from which the second-order rate constant was
determined from the slope (Figure 5, Inset, Table 2). In the
such as acetic acid (AcOH) to the superoxide complex 2O
preparative-scale reaction, the corresponding phosphine oxide
2
1
rapidly afforded the copper(II)-acetate complex 2OAc and H2O2
(∼50%) (Scheme 4, R = Ac). Furthermore, a largely negative
ΔS⧧ value (−143 3 J K−1 mol−1) was obtained in the Eyring
plot analysis shown in Figure 4, which also supports the
bimolecular reaction.
was obtained in a 86% yield based on 2O ( H NMR yield). The
2
reactions of a series of p-substituted-triphenylphosphine
derivatives P(ArY)3 (Y = OMe, H, F, and Cl) were also
examined to get insight into the reaction mechanism as shown
in Supporting Information, Figure S19−S22, and the second-
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Table 2. Second-Order Rate Constants for the Reaction of 2O with P(ArY)3 in Acetone at −85 °C
Article
2
p-substituent
102 k2/M−1 s−1
OMe
64
Me
H
F
Cl
0.67 0.004
1
42 0.8
7.2 0.1
1.5 0.9
order rate constants thus obtained are listed in Table 2. In this
case, the plot of log k2 against the Hammett constant σp
provides a linear correlation with a negative slope (ρ = −4.3,
Figure 6). This suggests that the superoxide complex also has
an electrophilic character in nature.
similar phenomenon was observed in the reaction of a
superoxide copper(II) complex supported by HIPT3tren and
PhSMe.48
CONCLUSION
■
In this study, the reactions of 2O with a series of external
2
substrates were examined to evaluate the intrinsic reactivity of
the superoxide complex supported by the tridentate ligand L
(Chart 1). On the basis of the reactivity of 2O with a series of
2
one-electron reductants with various Eox, the reduction
potential of 2O was estimated to be Ered = (0.19 0.07) V
2
vs SCE. In the reaction with a hydrogen atom donor such as
TEMPO-H, a simple HAT (hydrogen atom transfer) reaction
proceeded to give the corresponding hydroperoxide complex
LCuII−OOH (2OOH). In this case, intramolecular ligand
hydroxylation did not proceed. On the other hand, the reaction
with phenols (XArOH) gave the corresponding phenolate
adducts LCuII−OXAr instead of 2OOH. Kinetic analysis has
X
suggested an acid−base reaction between 2O and ArOH. The
2
reaction of 2O with a series of triphenylphosphine derivatives
2
gave the corresponding triphenylphosphine oxides via an
electrophilic adduct formation mechanism with a Hammett
value ρ = −4.3. In this case, CuII−O• type intermediate may be
generated by the O−O bond homolysis from a putative CuII−
O−O-•+PPh3 adduct intermediate.
Figure 6. Hammett plot for the reaction of 2O with P(ArY)3 in
acetone at −85 °C.
2
It is interesting to note that the reactivity of 2O is quite
2
different from that of (TMG3tren)CuII−OO•. The superoxide
Recently, Nam and co-workers reported the oxygen atom
transfer (OAT) reaction from a chromium(III)-superoxide
complex 2O itself can induce intramolecular aliphatic ligand
2
complex supported by a macrocyclic TMC ligand, [CrIII(O2 )-
•
hydroxylation, whereas no ligand hydroxylation product is
obtained from the hydroperoxide complex 2OOH (Scheme 3a).
On the other hand, the superoxide complex (TMG3tren)CuII−
OO• does not give any ligand hydroxylation products, but the
hydroperoxide complex (TMG3tren)CuII−OOH does (Scheme
3b). Furthermore, the reaction of (TMG3tren)CuII−OO• with
phenol derivatives causes a HAT reaction to provide several
oxidation/oxygenation products from the phenol substrates in
addition to the ligand hydroxylation product.36 On the other
(TMC)(Cl)]+, to triphenylphosphine, where they confirmed
generation of [CrIV(O)(TMC)(Cl)]+ together with triphenyl-
phosphine oxide as the products.47 These products may be
produced by homolytic O−O bond cleavage from a (TMC)-
(Cl)CrIII−O−O−•+PPh3 adduct intermediate.47 If the OAT
reaction from 2O to P(ArY)3 proceeds in a similar manner, a
2
CuII−O• intermediate (Type D in Scheme 1) might be
generated. However, such a reactive intermediate could not be
detected in the present reaction.
hand, the reaction of 2O and phenols simply affords the
2
The reaction of 2O with thioanisole (PhSMe) was also
2
phenolate adducts 2OAr. These differences in reactivity between
2O and (TMG3tren)CuII−OO• could be attributed in part to
2
examined. In this case, however, no oxygenation product
(Ph(Me)SO) was obtained, but 2O was converted to the
2
the difference in the coordination number and geometry (four-
coordinate/tetrahedral vs five-coordinate/trigonal bipyramidal)
as well as to the difference in the kind of donor atoms
(alkylamine and pyridine nitrogen atoms vs imine (guanidine)
nitrogen atoms). Such ligand effects on the reactivity of the
superoxide complexes should be considered in the mechanistic
studies of the copper monooxygenases.
copper(I) stating material as shown in Supporting Information,
Figure S23. The result can be explained by the mechanism
shown in Scheme 5. The O2-bindng to the copper(I) complex 1
is reversible as demonstrated in our previous study,39 and
addition of PhSMe to LCuI competes with the O2-binding. A
Scheme 5
ASSOCIATED CONTENT
■
S
* Supporting Information
Further details are given in Figures S1−S23. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: shinobu@mls.eng.osaka-u.ac.jp.
■
Notes
The authors declare no competing financial interest.
10436
dx.doi.org/10.1021/ic401261z | Inorg. Chem. 2013, 52, 10431−10437

Inorganic Chemistry
Article
(28) Gherman, B.; Heppner, D.; Tolman, W.; Cramer, C. J. Biol.
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ACKNOWLEDGMENTS
■
The present work was financially supported by Grant-in-Aids
for Scientific Research on Innovative Areas “Molecular
Activation Directed toward Straightforward Synthesis” (No.
22105007) and “Stimuli-responsive Chemical Species” (No.
24109015) and a Grant-in-Aid for Exploratory Research (No.
25620044) from the Ministry of Education, Culture, Sports,
Science and Technology, Japan. The authors thank Dr. Kei
Ohkubo and Prof. Shunichi Fukuzumi for their help in the
measurements of EPR spectra.
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