Characterization of a thiolato iron(III) peroxy dianion complex

Article abstract of DOI:10.1002/anie.201203602

Nucleophilic oxidant: The reaction between a thiolato iron(II) complex 1 and superoxide in aprotic solvent at -90 °C yields a novel thiolato iron(III) peroxide intermediate 2, which exhibits unusually high nucleophilic reactivity. Compound 2 is an isomer of the thiolato iron(II) superoxide intermediate that is invoked in the reaction between superoxide reductase and superoxide. Copyright

Full text of DOI:10.1002/anie.201203602

Angewandte
Chemie
DOI: 10.1002/anie.201203602
Reactive Intermediates
Characterization of a Thiolato Iron(III) Peroxy Dianion Complex**
Aidan R. McDonald, Katherine M. Van Heuvelen, Yisong Guo, Feifei Li, Emile L. Bominaar,
Eckard Mꢀnck,* and Lawrence Que Jr.*
Thiolate ligation to iron plays a vital role in the enzymatic
deactivation of reactive oxygen species. Superoxide reductase
(SOR) found in microaerophiles catalyzes the reduction of
superoxide (O2Cꢀ), yielding H2O2[1] and has an active site that
consists of an iron center with four
RS-FeIII(h1-OOꢀ) complex. Herein, we describe the spectro-
scopic characterization of a synthetic complex that serves to
model the putative RS-FeIII(h1-OOꢀ) intermediate found in
SOR.
equatorial His ligands and an axial
Cys ligand. The thiolate is proposed
Table 1: Properties of SOR and related RS-FeIII(OOX) complexes.
ꢀ
ꢀ
lmax [nm]
r (Fe S) [ꢀ] r (Fe OO) [ꢀ]
ꢀ
to stabilize the O O bond of RS-
(e, [Lmolꢀ1 cmꢀ1])
FeIII(h1-OO(ꢀ/H))
intermediates
wt-SORox [RS-FeIII(Glu)][3c,9a]
wt-SORred +superoxide[3]
E114 A-SORox +H2O2
[RS-FeIII(OOH)][3b,9b]
644 (1900)
600 (2800)
560
2.42–2.46
ꢀ
and to weaken the Fe (OO) bond
to facilitate formation of H2O2.[1,2]
Evidence for an intermediate in the
reaction between O2Cꢀ and SOR has
been obtained, which exhibits a visi-
ble absorption feature at about
600 nm.[3] Pulse radiolysis studies
showed diffusion-controlled pH-
independent formation of the inter-
mediate, while its decay was found
to be pH-dependent. These results
led to the postulation of the inter-
mediate as an RS-FeII(OOC) adduct
2.5
2.0
chloroperoxidase
2.4
1.9
Cpd 0[10]
2 [FeIII(TMCS)(h1-OOꢀ)]
[FeIII(cyclam-PrS)(OOH)]+[4c]
[FeIII(SMe2N4tren)(OOH)]+[4a,h]
[FeIII([15]aneN4)(SAr)(OOR)]+[4b,d]
460 (6100), 610 (1200)
535 (1350)
452 (2780)
2.41
1.89
2.33
1.86
ca. 525
2.29–2.32 1.82–1.85
[FeIII(Me4[15]aneN4)(SPh)(OOR)]+[4f,g] 340 (3500), 405 (2300), 650 (2300)
or the isoelectronic RS-FeIII(OOꢀ); however its short lifetime
has made it difficult to establish the iron oxidation state
experimentally. We have thus endeavored to obtain a syn-
thetic analogue of this intermediate.
[FeII(TMCS)]PF6 (1) acts as an ideal mimic of the SOR
active site because it contains four equatorial N ligands and an
axial S bound to the iron center (Scheme 1).[5] Compound
A number of synthetic non-heme RS-FeIII(h1-OOX) (X =
H, alkyl) complexes have been reported recently,[4] providing
insights into the role thiolate ligation plays in modulating the
reactivity of peroxide complexes, and the nature of the RS-
FeIII(h1-OOH) intermediate observed in SOR (Table 1).
However, there are no reports detailing the isolation of an
Scheme 1. Equilibrium between 1 and 2.
[*] Dr. A. R. McDonald, Dr. K. M. Van Heuvelen, Dr. F. Li,
Prof. Dr. L. Que Jr.
Department of Chemistry, University of Minnesota
207 Pleasant Street SE, Minneapolis, MN 55455 (USA)
E-mail: larryque@umn.edu
1 reacted with KO2 (dissolved in pure DMF in the presence of
2 equiv of [18]crown-6) at ꢀ908C in a 4:1 THF/DMF solvent
mixture. The characteristic UV feature of 1 (lmax = 320 nm,
Figure 1) disappeared over the course of 10 s and was
replaced by two new intense features (lmax = 460, 610 nm),
which were assigned to transient species 2. The visible
features achieved maximum intensity when an excess (> 50-
fold) of KO2 was used. Intermediate 2 was reasonably stable
at ꢀ908C, decaying over the course of about 3 h to produce
1 nearly quantitatively (Supporting Information, Figure S1).
Species 2 could then be regenerated by replenishing the KO2.
These observations suggest that superoxide binding to 1 is
reversible, with the decay of 2 presumably reflecting the loss
of KO2 owing to its gradual disproportionation in the reaction
Dr. Y. Guo, Prof. Dr. E. L. Bominaar, Prof. Dr. E. Mꢁnck
Department of Chemistry, Carnegie Mellon University
4400 Fifth Avenue, Pittsburgh, PA 15213 (USA)
E-mail: emunck@cmu.edu
[**] This work was supported by the US National Science Foundation
(grant CHE1058248 to L.Q.) and the US National Institutes of
Health (grant EB001475 to E.M. and postdoctoral fellowships to
A.R.McD. (GM087895) and K.M.V.H. (GM093479). XAS data were
collected at beamline X3B of the National Synchrotron Light Source
at the Brookhaven National Laboratory, which is supported by the
U.S. NIH and DOE.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201203602.
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
complex. The 57Fe magnetic hyperfine interactions as well as
the isomer shift of 2 obtained from Mçssbauer spectra
(Figure 2) establish that the iron center is in the high-spin
ferric state.
Figure 1. UV/Vis spectrum of 1 (black trace, 0.2 mm in 4:1 THF/DMF
(v/v) at ꢀ908C) that reacted with KO2 to yield 2 (gray trace). Molar
absorptivity values were calculated using a combination of UV/Vis and
Mçssbauer experiments. Inset: X-band EPR spectrum of 2 in 4:1 THF/
DMF. T=20 K; microwave power, 2 mW, microwave frequency,
9.645 GHz, modulation amplitude, 10 G, modulation frequency,
100 Hz. Gray line is a theoretical spectrum for an S=5/2 species with
E/D=0.08, and E/D distribution s(E/D)=0.03 (see text). The sharp
feature marked with * arises from minor contaminant (ca. 0.5% of
Fe). The high-field region is not shown as it is dominated by the
intense absorption of free KO2.
Figure 2. 4.2 K Mçssbauer spectra of 2 recorded in parallel applied
magnetic fields indicated in the figure. The gray curves are spectral
simulations using the S=5/2 spin-Hamiltonian of Equation (1) with
medium and a shift of the equilibrium back to 1 (Scheme 1).[6]
Similar chemistry has been reported for a crown-ether-
functionalized porphyrin ligand that facilitates the reversible
formation of a heme–FeIII(OO) complex from the heme–FeII
precursor and KO2.[7]
D=2.5 cmꢀ1, E/D=0.08, gx,y,z =2.0, d=0.71(3) mmsꢀ1
,
DEQ =ꢀ1.9(1) mmsꢀ1, h=ꢀ0.20, Ax/gnbn =Ay/gnbn =ꢀ17.5(4) T, Az/
gnbn =ꢀ21.0(5) T.
The highly chromophoric nature of 2 suggests that the iron
center has been oxidized to FeIII, concomitant with the
reduction of the superoxide ligand to the peroxide level.
However the electronic absorption spectrum of 2 is quite
distinct from those reported for related non-heme RS-FeIII-
(OOX) (X = H or alkyl) complexes (Table 1). While all
complexes exhibit broad absorption features in the 500–
800 nm region typically associated with peroxo-to-FeIII
charge-transfer transitions, 2 has an additional feature at
460 nm (e = 6100 Lmolꢀ1 cmꢀ1) that is sharper and more
intense (Figure 1). For comparison, treatment of [FeII(TMC)-
(OTf)]+ with KO2 afforded a product with a broad band at
850 nm (Supporting Information, Figure S2), which is nearly
identical to that observed for [FeIII(TMC)(h2-OO)]+ in
CH3CN at ꢀ408C.[8] It would thus appear that the more
basic axial ligand of 2 is required to elicit its novel absorption
features. We therefore postulate that 2 represents a thus far
unprecedented example of an RS-FeIII(h1-OOꢀ) complex.
EPR spectra of 2 revealed broad features belonging to an
S = 5/2 species (Figure 1, inset). The spectra indicate that the
rhombicity parameter, E/D, is distributed around a mean
value of E/D ꢁ 0.08. The gray curve is an illustrative
simulation for the major contributing species: the feature at
g = 7.9 belongs to the MS =ꢂ 1/2 ground doublet and the
resonance g = 5.75 results from the MS =ꢂ 3/2 excited state.
The feature marked with the star is a minor rhombic
contaminant (ca. 0.5% of total Fe; see the Supporting
We have simulated the 4.2 K Mçssbauer spectra of 2 using
the S = 5/2 spin Hamiltonian (parameters listed in the caption
of Figure 2):
2
2
2
h ¼ DðSz ꢀ35=4Þ þ EðSx ꢀSy Þ þ bS g B þ S A Iꢀgnbn B I þ hQ
ð1Þ
where D and E are the axial and rhombic zero-field splitting
parameters, A is the 57Fe magnetic hyperfine tensor, and hQ
describes the nuclear quadrupole interactions. DEQ = (eQVzz/
12)(1+h2/3)1/2 is the quadrupole splitting, while h = (VxxꢀVyy)/
Vzz is the asymmetry parameter of the electric field gradient
tensor. The shape of the Mçssbauer spectrum recorded in an
applied field, B = 50 mT (Supporting Information, Figure S6),
just like the EPR spectrum, indicates that E/D is distributed;
we were not able describe the E/D distribution by a symmetric
function such as a Gaussian, and therefore we have focused
the Mçssbauer analysis on the high field spectra (B ꢃ 2 T),
which are essentially independent of E/D. The 8.0 T spectrum
reveals that 2 represents at least 95% of total Fe. Importantly,
2 has a negative quadrupole splitting, DEQ = ꢀ1.9 mmsꢀ1, the
largest value yet observed for a high-spin [FeIII(TMC)]
complex.[8b,11] The 57Fe A tensor of 2 is characteristic of
high-spin FeIII. Its isotropic component, Aiso/gnbn = ꢀ18.7 T
(Aiso = (Ax + Ay + Az)/3), is comparable to the ꢀ20.0 T value
reported for the high-spin FeIII(TMC)(h1-OOH) complex,[8b]
and the smaller value observed for 2 can be attributed to the
presence of the more covalent thiolate ligand. Interestingly,
Information, Figure S5, for more details).[8b] The S = 5/2
II
species could arise from a ferromagnetically coupled (SFe
=
2/Ssuperoxide = 1/2) center or from a high-spin FeIII peroxide
2
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
the D and (dominant) E/D values of 2 are quite similar to
those observed for [FeIII(TMC)(h1-OOH)]2+ (D =+ 2.5 cmꢀ1,
E/D = 0.097).[8b] However the isomer shift of 2, d =
0.71(3) mmsꢀ1, is distinctly larger than the d = 0.51 mmsꢀ1
observed for [FeIII(TMC)(h1-OOH)]2+.[8b]
a six-coordinate structure, with a pentadentate TMCS and an
h1-end-on peroxo moiety trans to the thiolate ligand.[16]
As the RS-FeIII(h1-OOꢀ) complex would be expected to
be prone to protonation, the reactivity of 2 towards weak
acids was probed. The addition of 100 equiv 2,2,2-trifluoroe-
thanol (TFE, pKa = 12.5) to a solution of 2 resulted in the
rapid (10 s) disappearance of the features assigned to 2 and
the formation of new features (lmax = 550, 720 nm) assigned to
a new species 3 (Supporting Information, Figure S3). Under
the same conditions, addition of 100 equiv of stronger acids
such as ammonium acetate (pKa = 9.2) or pyridinium triflate
(pKa = 5.2) also yielded intermediate 3 on the same time
scale. In contrast, the reaction between 2 and 100 equiv
MeOH (pKa = 15.2) did not yield 3 but instead afforded 1,
presumably due to accelerated decay of KO2 by disproportio-
nation (Supporting Information, Figure S7).
The Mçssbauer parameters of 2 reveal a high-spin ferric
center with unique properties. It has the largest isomer shift
for any FeIII peroxide complex reported thus far,[8b,12] a large
and negative DEQ (with the largest component of the field
gradient along z), and an 57Fe A-tensor that is rather
anisotropic for a high-spin FeIII center.[13] These three proper-
ties have a common origin, as may be inferred from the
following considerations. For a high-spin FeIII center, the five
d orbitals are occupied by a electrons. To explain the large
and negative DEQ, we postulate transfer of b electron density
from the two filled peroxo p* orbitals to the empty bdxz(Fe)
and bdyz(Fe) orbitals. If only one orbital were involved (dxz or
dyz), a positive DEQ would result, with the largest component
of the quadrupole tensor in the xy plane, in contrast to what is
observed. However, if bdxz(Fe) and bdyz(Fe) were equally
populated, a negative DEQ with the major component along z
would result, as observed.[14] As the spin-dipolar contribution
to 57Fe A tensor is proportional to the valence part of the
quadrupole tensor, we expect the donation to increase the
magnitude of Az and to decrease the magnitude of Ax,y.
Indeed, we observe that j Ax,y j<j Az j . Finally, electron
donation by the peroxo ligand into bdxz and bdyz orbitals
enhances the d electron density at the iron, thereby imbuing
the iron center with some ferrous character and resulting in an
increase in its isomer shift as observed.
The behavior of 1 with KO2 is notably different from the
RS-FeII complexes studied by Kovacs, for which no reaction
with KO2 was observed until the addition of MeOH, leading
to the generation of RS-FeIII(h1-OOH) intermediates.[4a,c] This
was true even for the complex of the N-(3-mercaptopropyl)-
cyclam ligand,[4c] which is closely related to TMCS. In
contrast, superoxide reduction readily occurred in the reac-
tion between 1 and KO2 in an aprotic solvent, to generate 2,
which could be easily protonated to yield a postulated RS-
FeIII(h1-OOH) intermediate (3) (Supporting Information,
Scheme S1).
Reactivity studies provided further insights into the
properties of the peroxide ligand in 2. Complex 2 did not
ꢀ
react at ꢀ908C with substrates that contain weak C H bonds,
X-ray absorption spectroscopy (XAS) provided insight
into the structural and electronic properties of 2. The XAS
edge energy of 7123.1 eV observed for 2 falls at the low
energy end of the range reported for FeIII(OO) complexes (ca.
7123 to 7125 eV), consistent with an FeIII center ligated by
highly basic thiolate and peroxide donors (Supporting Infor-
mation, Figure S8). There is a small pre-edge peak arising
from a 1s!3d transition at 7113.6 eV with a peak area of 11.0
units (Supporting Information, Table S1), suggesting the
presence of a fairly distorted six-coordinate FeIII center.[15]
Analysis of EXAFS data for 2 yielded a principal shell of
four N/O scatterers at 2.17 ꢀ, which are attributed to the
equatorial nitrogen donors of the TMCS ligand. This distance
resembles that for [FeIII(TMC)(h1-OOH)]2+ (2.15–2.16 ꢀ)
more closely than for its conjugate base [FeIII(TMC)(h2-
OO)]+ (2.20–2.23 ꢀ).[8b,c] The inclusion of an S scatterer at
2.41 ꢀ significantly improved the quality of the fit, indicating
coordination of the thiolate moiety to the iron center.
such as dihydroanthracene, thus demonstrating that the
bound peroxo moiety did not possess any electrophilic
character. Its nucleophilic nature, however, was demonstrated
in its reactivity towards electrophilic substrates. Menadione
(2-methyl-1,4-naphthoquinone) is a substrate often used for
this purpose, affording menadione epoxide (2,3-epoxy-2-
methyl-1,4-naphthoquinone) in high yield (Supporting Infor-
mation, Scheme S2).[17] For example, Valentine showed that
[FeIII(F20TPP)(h2-OO)]ꢀ (F20TPP = meso-tetrakis(pentafluor-
ophenyl)porphinato) did not react with menadione in CH3CN
at 258C but afforded a 70% yield of the epoxide product by
change of solvent to dimethyl sulfoxide (DMSO).[17a,c] The
latter reactivity was proposed to result from the binding of
DMSO to the FeIII center, converting the h2-side-on peroxo
moiety to its h1-end-on isomer. When 2 was treated with
menadione at ꢀ908C in 4:1 THF/DMF, menadione epoxide
was obtained in 100 (ꢂ 20)% yield within 60 s, supporting the
assignment of 2 as an h1-end-on peroxide complex.
ꢀ
However the Fe S distance found for 2 is rather long, relative
Aldehyde substrates are also useful probes of metal
peroxide nucleophilicity.[18] At ꢀ908C 2 reacted with 20 equiv
of 2-phenylpropionaldehyde (PPA) within 5 s, yielding ace-
tophenone and formate according to GC-MS. Accurate
kinetic analysis, and thus determination of second order
rate constants (k2), at such rapid rates was not possible;
however 2 was clearly a very active reactant for nucleophilic
oxidation reactions. UV/Vis analysis of the reaction between
2 and PPA (Supporting Information, Figure S4) showed
isosbestic behavior and a clean conversion to a new FeIII
product that displayed features typical of an RS-FeIII complex
to those observed for other synthetic RS-FeIII(OOX) model
complexes (ca. 2.30 ꢀ), but comparable to values associated
with biological RS-FeIII(OOX) intermediates (Table 1). For
the peroxo ligand, we considered two possible binding modes,
h2-side-on and h1-end-on. Attempts to model 2 using an h2-
side-on peroxo moiety yielded unreasonably large s2 values
(> 15; Supporting Information, Table S2). In contrast, the
inclusion of a single O/N scatterer at 1.89 ꢀ significantly
improved the quality of the fit (Supporting Information,
Figure S9, Table S2). Taken together, the EXAFS fits favor
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
(lmax = 480 nm).[19] In stark contrast, we found that [FeIII-
(TMC)(h2-OO)]+ was not reactive towards PPA at ꢀ908C in
4:1 THF/DMF, in agreement with Namꢁs earlier report that
side-on [FeIII(TMC)(h2-OO)]+ was not reactive towards PPA
at ꢀ408C.[8c] On the other hand, the end-on hydroperoxide
analogue [FeIII(TMC)(h1-OOH)]2+ reacted with PPA over the
course of 800 s at ꢀ408C.[8c] Based on the accumulated
observations on the reactivity of all the above FeIII(L)(OO)
complexes, it is clear that 2 contains a very reactive
nucleophilic peroxide ligand, which reacts rapidly, even at
ꢀ908C. These results further support our assignment of 2 as
an RS-FeIII(h1-OOꢀ) complex.
[3] a) M. Lombard, C. Houꢃe-Levin, D. Touati, M. Fontecave, V.
Niviꢂre, Biochemistry 2001, 40, 5032 – 5040; b) C. Mathꢃ, T. A.
Mattioli, O. Horner, M. Lombard, J.-M. Latour, M. Fontecave, V.
Niviꢂre, J. Am. Chem. Soc. 2002, 124, 4966 – 4967; c) V. Niviꢂre,
M. Asso, C. O. Weill, M. Lombard, B. Guigliarelli, V. Favaudon,
C. Houꢃe-Levin, Biochemistry 2004, 43, 808 – 818; d) F. Bonnot,
T. Molle, S. Mꢃnage, Y. Moreau, S. Duval, V. Favaudon, C.
Houꢃe-Levin, V. Niviꢂre, J. Am. Chem. Soc. 2012, 134, 5120 –
5130; e) E. D. Coulter, J. P. Emerson, D. M. Kurtz, Jr., D. E.
Cabelli, J. Am. Chem. Soc. 2000, 122, 11555 – 11556; f) J. P.
Emerson, E. D. Coulter, D. E. Cabelli, R. S. Phillips, D. M.
Kurtz, Jr., Biochemistry 2002, 41, 4348 – 4357.
[4] a) J. Shearer, R. C. Scarrow, J. A. Kovacs, J. Am. Chem. Soc.
2002, 124, 11709 – 11717; b) D. Krishnamurthy, G. D. Kasper, F.
Namuswe, W. D. Kerber, A. A. N. Sarjeant, P. Moenne-Loccoz,
D. P. Goldberg, J. Am. Chem. Soc. 2006, 128, 14222 – 14223; c) T.
Kitagawa, A. Dey, P. Lugo-Mas, J. B. Benedict, W. Kaminsky, E.
Solomon, J. A. Kovacs, J. Am. Chem. Soc. 2006, 128, 14448 –
14449; d) F. Namuswe, G. D. Kasper, A. A. N. Sarjeant, T.
Hayashi, C. M. Krest, M. T. Green, P. Moenne-Loccoz, D. P.
Goldberg, J. Am. Chem. Soc. 2008, 130, 14189 – 14200; e) Y.
Jiang, J. Telser, D. P. Goldberg, Chem. Commun. 2009, 6828 –
6830; f) F. Namuswe, T. Hayashi, Y. Jiang, G. D. Kasper, A. A. N.
Sarjeant, P. Moenne-Loccoz, D. P. Goldberg, J. Am. Chem. Soc.
2010, 132, 157 – 167; g) J. Stasser, F. Namuswe, G. D. Kasper, Y.
Jiang, C. M. Krest, M. T. Green, J. Penner-Hahn, D. P. Goldberg,
Inorg. Chem. 2010, 49, 9178 – 9190; h) E. Nam, P. E. Alokolaro,
R. D. Swartz, M. C. Gleaves, J. Pikul, J. A. Kovacs, Inorg. Chem.
2011, 50, 1592 – 1602.
In summary, the reaction between an RS-FeII complex
1 and KO2 at ꢀ908C in aprotic solvent generates a reversible
adduct 2 that is best described as an RS-FeIII(h1-OOꢀ)
complex on the basis of its spectroscopic properties. We
postulate that 2 represents the first synthetic model of the
initial SOR-superoxide adduct prior to its protonation in the
SOR catalytic cycle. Two recent DFT studies favor an RS-
FeII(OOC) description for this adduct using simplified active
sites that did not include second sphere residues.[3d,20] How-
ever our results provide experimental evidence that the
isomeric RS-FeIII(h1-OOꢀ) complex can be generated and
stabilized in an aprotic medium and in fact exhibits an
absorption band at 610 nm like that found for the SOR
intermediate.[3] For 2, the dianionic peroxo ligand may be
stabilized in part by the potassium ion introduced through the
use of KO2. Related porphyrin–FeIII(OOꢀ) complexes have
been reported, but they do not have an axial thiolate
ligand.[7,21] 2, therefore, is a unique example of a thiolato
iron(III) peroxy dianion model compound that mimics the
structure and function of the postulated RS-FeIII(h1-OOꢀ)
intermediates in SOR and the P450 family. We have also
shown that the peroxide ligand on 2 is highly nucleophilic in
nature and is readily protonated by weak acids, consistent
with a possible role for this species in the SOR cycle.
Furthermore, 2 reacts rapidly with carbonyl compounds, even
at ꢀ908C, making it relevant to the nucleophilic chemistry
postulated for corresponding RS-FeIII(h1-OOꢀ) intermediates
in the catalytic cycles of heme–thiolate enzymes, such as
aromatase and NO synthase.[18,22]
[5] A. T. Fiedler, H. L. Halfen, J. A. Halfen, T. C. Brunold, J. Am.
Chem. Soc. 2005, 127, 1675 – 1689.
[6] As peroxide is a byproduct of superoxide disproportionation,
control experiments between 1 and H2O2 or Na2O2 were carried
out in THF/DMF at ꢀ908C. In neither case was a reaction
observed over the course of 1 h.
[7] a) K. Dꢄrr, B. P. Macpherson, R. Warratz, F. Hampel, F. Tuczek,
M. Helmreich, N. Jux, I. Ivanovic-Burmazovic, J. Am. Chem.
Soc. 2007, 129, 4217 – 4228; b) K. Dꢄrr, N. Jux, A. Zahl, R.
van Eldik, I. Ivanovic-Burmazovic, Inorg. Chem. 2010, 49,
11254 – 11260; c) K. Duerr, J. Olah, R. Davydov, M. Kleimann,
J. Li, N. Lang, R. Puchta, E. Hubner, T. Drewello, J. N. Harvey,
N. Jux, I. Ivanovic-Burmazovic, Dalton Trans. 2010, 39, 2049 –
2056.
[8] a) J. Annaraj, Y. Suh, M. S. Seo, S. O. Kim, W. Nam, Chem.
Commun. 2005, 4529 – 4531; b) F. Li, K. K. Meier, M. A.
Cranswick, M. Chakrabarti, K. M. Van Heuvelen, E. Mꢄnck,
L. Que, Jr., J. Am. Chem. Soc. 2011, 133, 7256 – 7259; c) J. Cho, S.
Jeon, S. A. Wilson, L. V. Liu, E. A. Kang, J. J. Braymer, M. H.
Lim, B. Hedman, K. O. Hodgson, J. S. Valentine, E. I. Solomon,
W. Nam, Nature 2011, 478, 502 – 505.
Received: May 9, 2012
Revised: June 19, 2012
Published online: && &&, &&&&
[9] a) A. P. Yeh, Y. Hu, F. E. Jenney, M. W. W. Adams, D. C. Rees,
Biochemistry 2000, 39, 2499 – 2508; b) G. Katona, P. Carpentier,
V. Niviꢂre, P. Amara, V. Adam, J. Ohana, N. Tsanov, D.
Bourgeois, Science 2007, 316, 449 – 453.
[10] K. Kꢄhnel, E. Derat, J. Terner, S. Shaik, I. Schlichting, Proc.
Natl. Acad. Sci. USA 2007, 104, 99 – 104.
Keywords: bioinorganic chemistry · iron · peroxo intermediates ·
reactive intermediates · thiolate complexes
.
[11] J. F. Berry, E. Bill, E. Bothe, F. Neese, K. Wieghardt, J. Am.
Chem. Soc. 2006, 128, 13515 – 13528.
[12] M. Costas, M. P. Mehn, M. P. Jensen, L. Que, Jr., Chem. Rev.
2004, 104, 939 – 986.
[1] a) V. Niviꢂre, F. Bonnot, D. Bourgeois in Handbook of Metal-
loproteins, Vols. 4 & 5 (Ed.: A. Messerschmidt), Wiley, Chi-
chester, 2011, pp. 246 – 258; b) A. S. Pereira, P. Tavares, F.
Folgosa, R. M. Almeida, I. Moura, J. J. G. Moura, Eur. J. Inorg.
Chem. 2007, 2569 – 2581; c) D. M. Kurtz, Jr., Acc. Chem. Res.
2004, 37, 902 – 908.
[2] a) C. Mathꢃ, C. O. Weill, T. A. Mattioli, C. Berthomieu, C.
Houꢃe-Levin, E. Tremey, V. Niviꢂre, J. Biol. Chem. 2007, 282,
22207 – 22216; b) J. A. Kovacs, L. M. Brines, Acc. Chem. Res.
2007, 40, 501 – 509.
[13] G. Lang, Q. Rev. Biophys. 1970, 3, 1 – 60.
[14] The valence contribution to the principal components of the
quadrupole tensor (Q’xx,yy,zz, in atomic units) is proportional to
(ꢀ2/7, + 4/7, ꢀ2/7) and (+ 4/7, ꢀ2/7, ꢀ2/7) for an electron in dxz
and dyz, respectively. Adding these contributions yields (2/7, 2/7,
ꢀ4/7). See: P. Gꢄtlich, R. Link, A. Trautwein, Mçssbauer
4
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
Spectroscopy and Transition Metal Chemistry, Springer, Berlin,
1978.
[15] S. DeBeer George, T. Petrenko, F. Neese, J. Phys. Chem. A 2008,
112, 12936 – 12943.
[16] Because of the importance of vibrational information, we made
a number of attempts to obtain such data to probe the peroxide
binding mode in 2, but these experiments were all unsuccessful.
These experiments are described in the Supporting Information.
[17] a) M. Selke, M. F. Sisemore, J. S. Valentine, J. Am. Chem. Soc.
1996, 118, 2008 – 2012; b) M. F. Sisemore, J. N. Burstyn, J. S.
Valentine, Angew. Chem. 1996, 108, 195 – 196; Angew. Chem. Int.
Ed. Engl. 1996, 35, 206 – 208; c) M. Selke, J. S. Valentine, J. Am.
Chem. Soc. 1998, 120, 2652 – 2653.
[19] a) P. Kennepohl, F. Neese, D. Schweitzer, H. L. Jackson, J. A.
Kovacs, E. I. Solomon, Inorg. Chem. 2005, 44, 1826 – 1836;
b) M. R. Bukowski, K. D. Koehntop, A. Stubna, E. L. Bominaar,
J. A. Halfen, E. Mꢄnck, W. Nam, L. Que, Jr., Science 2005, 310,
1000 – 1002.
[20] A. Dey, F. E. Jenney, M. W. W. Adams, M. K. Johnson, K. O.
Hodgson, B. Hedman, E. I. Solomon, J. Am. Chem. Soc. 2007,
129, 12418 – 12431.
[21] J.-G. Liu, Y. Shimizu, T. Ohta, Y. Naruta, J. Am. Chem. Soc. 2010,
132, 3672 – 3673.
[22] a) M. R. C. M. Akhtar, D. L. Corina, J. N. Wright, Biochem. J.
1982, 201, 569 – 580; b) K. R. Korzekwa, W. F. Trager, S. J. Smith,
Y. Osawa, J. R. Gillette, Biochemistry 1991, 30, 6155 – 6162;
c) R. A. Pufahl, J. S. Wishnok, M. A. Marletta, Biochemistry
1995, 34, 1930 – 1941; d) J. J. Woodward, M. M. Chang, N. I.
Martin, M. A. Marletta, J. Am. Chem. Soc. 2009, 131, 297 – 305.
[18] D. L. Wertz, J. S. Valentine, Struct. Bonding (Berlin) 2000, 97,
38 – 60.
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

.
Angewandte
Communications
Communications
Reactive Intermediates
Nucleophilic oxidant: The reaction
between a thiolato iron(II) complex 1 and
superoxide in aprotic solvent at ꢀ908C
yields a novel thiolato iron(III) peroxide
intermediate 2, which exhibits unusually
high nucleophilic reactivity. Compound 2
is an isomer of the thiolato iron(II)
superoxide intermediate that is invoked
in the reaction between superoxide
reductase and superoxide.
A. R. McDonald, K. M. Van Heuvelen,
Y. Guo, F. Li, E. L. Bominaar, E. Mꢁnck,*
L. Que*
&&&& — &&&&
Characterization of a Thiolato Iron(III)
Peroxy Dianion Complex
6
www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!