Contrasting cis and trans effects on the reactivity of nonheme oxoiron(IV) complexes

Article abstract of DOI:10.1002/anie.200704228

(Chemical Equation Presented) Position determines properties: The oxidative properties of [Fe^IV(O)(L)(X)] species (L = tetradentate N4 ligand, X = monodentate ligand) depend on the position of the X ligand. The Fe=O unit is a poorer oxidant wit

Full text of DOI:10.1002/anie.200704228

Communications
DOI: 10.1002/anie.200704228
Iron–Oxo Complexes
Contrasting cis and trans Effects on the Reactivity of Nonheme
Oxoiron(IV) Complexes**
Yuming Zhou, Xiaopeng Shan, RubØn Mas-BallestØ, Michael R. Bukowski, Audria Stubna,
MrinmoyChakrabarti, Luke Slominski, Jason A. Halfen, Eckard Münck, and
Lawrence Que, Jr.*
Oxoiron(IV) species are often implicated as the key oxidants
in the catalytic cycles of oxygen-activating iron enzymes, both
heme[1] and nonheme.[2] For heme enzymes, the only site
available for significant ligand tuning is that trans to the oxo
ligand because of the planar tetradentate nature of the
common porphyrin cofactor. In contrast, the metal coordina-
tion environments in nonheme iron enzymes exhibit a greater
variability, in that different ligands can occupy sites either cis
or trans to the oxo group within this superfamily of enzymes.
This flexibility may serve as an additional means for tuning
the reactivity of the oxoiron(IV) unit.
oxoiron(IV) family, and thus serve as prototypes.[4] They
each have an easily displaceable MeCN ligand located cis and
trans, respectively, to the oxo group, which has been shown to
undergo ligand exchange reactions wherein the MeCN ligand
can be replaced by anions such as halides and carboxylates.[5]
For this study, the sixth ligand of choice is pyridine N-oxide
(PyO), since several 4-substituted derivatives are available to
allow a systematic investigation of substituent effects on
reactivity. Indeed, addition of 5 equivalents of PyO to a
solution of 1 in MeCN immediately broadens its signature
near-IR band at 720 nm into two poorly resolved features at
675 and 745 nm (Figure 1a and Figure S1 in the Supporting
Information), demonstrating that the d–d transitions of the
S = 1 oxoiron(IV) center[5d] are perturbed by the binding of
PyO. However, PyO addition to a solution of 2 in MeCN does
Synthetic nonheme oxoiron(IV) complexes have recently
been characterized, and the growing family of such complexes
demonstrates that polydentate nitrogen ligands with different
topologies can support the oxoiron(IV) center.[3] Herein, we
compare the reactivities of two synthetic nonheme oxo-
iron(IV) complexes supported by closely related ligands. The
tetradentate nature of these ligands leaves a sixth coordina-
tion site that is occupied by the solvent MeCN, which can
easily be displaced by pyridine N-oxides (PyOs), and we find
dramatic differences in reactivity trends depending on
whether the ligand at the sixth site is cis or trans to the oxo
group.
[FeIV(O)(tpa)(NCMe)]2+ (1; tpa = tris(2-pyridylmethyl)-
amine) and [FeIV(O)(tmc)(NCMe)]2+ (2; tmc = 1,4,8,11-tet-
ramethyl-1,4,8,11-tetraazacyclotetradecane) represent the
first two well-characterized complexes of the nonheme
[*] Dr. Y. Zhou, Dr. X. Shan, Dr. R. Mas-BallestØ, Dr. M. R. Bukowski,
Prof. Dr. L. Que, Jr.
Department of Chemistry and Center for Metals in Biocatalysis
University of Minnesota
Minneapolis, MN 55455 (USA)
Fax: (+1)612-624-7029
E-mail: que@chem.umn.edu
L. Slominski, Prof. Dr. J. A. Halfen
Department of Chemistry
University of Wisconsin Eau Claire
Eau Claire, WI 54702 (USA)
Dr. A. Stubna, M. Chakrabarti, Prof. Dr. E. Münck
Department of Chemistry
Carnegie Mellon University
Pittsburgh, PA 15213 (USA)
[**] This work was supported by the National Institutes of Health (GM-
33162 to L.Q. and EB-001475 to E.M.) and the National Science
Foundation (CHE-0615479 to J.A.H.).
Figure 1. Visible spectra of a) 1 (b, y axis downshifted by 0.05 unit
to provide a clearer view), 1-(OPy) (c) and b) 3 (b), 3-(OPy)
(c) generated at ꢀ208C in CH3CN.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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not affect its near-IR band at 820 nm, suggesting that PyO
cannot bind to 2. This observation can be rationalized by
invoking steric effects of the four N-methyl groups of the tmc
ligand, which are all oriented on one side of the macrocycle
opposite to the oxo atom and define a pocket that limits the
size of the sixth ligand.[4b]
Mössbauer sample affords a molar extinction coefficient of
260mꢀ1 cmꢀ1 for the 790-nm chromophore of 3.
Addition of 5 equivalents of PyO to 3 in MeCN results in
the splitting of the near-IR band into two components at 790
and 950 nm (Figure 1b). These spectral changes are analo-
gous to those observed for 2 upon complete displacement of
the MeCN ligand by a carboxylate or a pseudohalide[5a,b]
ligand and can be attributed to the dispersion of the three
ligand-field bands found in this region.[5d] Titration of 3 with
PyO shows that the spectral changes are complete with the
addition of 2.5 equivalents, demonstrating that PyO competes
Another nonheme ligand with four N donor groups
constrained to be in a plane is L8Py2 (see 3),[6] which has
two pyridine rings in place of two of the tertiary amine donors
in tmc to eliminate the steric constraints that prevented
binding of PyO to 2. The reaction of [FeII(L8py2)(OTf)]+
(OTf = trifluoromethanesulfonate) with 1 equivalent of
CH3CO3H in CH3CN at ꢀ408C generates a pale green
species 3 with a lmax at 790 nm (Figure 1b, dashed line). This
chromophore resembles those associated with 1, 2, and other
low-spin nonheme oxoiron(IV) complexes.[3,4] The formula-
tion of 3 is established by its high-resolution electrospray
ionization mass spectrum, in which the dominant ion cluster is
observed at m/z 517.0818 with a mass and isotope distribution
pattern corresponding to the [FeIV(O)(L8py2)(OTf)]+ ion
(calcd. m/z 517.0815) (Figure 2). The Mössbauer spectrum
=
well with the MeCN solvent for binding to the Fe O moiety
(Figures S3 and S4 in the Supporting Information). Further-
more, a Mössbauer spectrum of 3 with 5 equivalents of PyO
shows
a doublet with a smaller quadrupole splitting
(1.59 mmsꢀ1), demonstrating complete formation of the
PyO adduct under these conditions. Similar spectral shifts
are observed upon addition of 4-Me-, 4-MeO-, or 4-Cl-
substituted derivatives (Figure S5 and Table S1 in the
Supporting Information), but not for 4-O2N-PyO or 4-NC-
PyO. However, addition of any PyO shortens the lifetime of 3
(see below). Thus our accumulated results show that pyridine
N-oxides bind to 3.
Both 1 and 3 have significant lifetimes at ꢀ208C. In the
absence of added PyOs, the half-life of 1 is estimated to be
longer than 30 hours, whereas that of 3 is about 7 hours.
Addition of 5 equivalents of a particular pyridine N-oxide
decreases these values, but the effects are different for 1 and
3. The half-life of 1 is only slightly reduced by the addition of
4-MeO-PyO, but is cut by more than 20-fold with 4-O2N-PyO.
In contrast, the half-life of 3 decreases only threefold with
added 4-O2N-PyO but diminishes over 100-fold with 4-MeO-
=
PyO. Thus cis- and trans-ligated PyOs affect the Fe O unit in
dissimilar ways.
These contrasting effects of cis- and trans-ligated PyOs are
also manifested in the oxidations of benzyl alcohol and
diphenyl sulfide by 1 and 3, for which the organic products
were identified to be benzaldehyde and diphenyl sulfoxide,
respectively (Table S1 in the Supporting Information). No
pyridine was observed as a by-product for the reaction, so
PyO does not act as an oxo-atom donor in these reactions. The
oxidation rates were measured in the presence of various
PyOs (5 equiv) by monitoring the disappearance of the near-
IR chromophores. These results (Table S1) show that the
reactivity of 1 varies by at most a factor of 5 by the
introduction of a 4-substituent, whereby electron-donating
substituents decrease the oxidation rates relative to the
parent MeCN complex. In contrast, the oxidative reactivity of
3 changes by a factor of about 25 over the entire range of
substituents, and electron-donating groups accelerate the
reactions.
Figure 2. Dominant molecular ion cluster in the high-resolution elec-
trospray mass spectrum of 3.
of 3 exhibits a quadrupole doublet with d = 0.08 mmsꢀ1 and
DEQ = 1.79 mmsꢀ1 (Figure S2 in the Supporting Information).
Its isomer shift falls in the middle of the range established for
other low-spin oxoiron(IV) complexes with neutral support-
ing ligands (ꢀ0.04 to 0.17 mms)ꢀ1, which is consistent with the
two-amine, two-pyridine ligand combination.[3,4,7,8] Its quad-
rupole splitting, in contrast, is the largest found thus far for
this family of complexes; it is larger by 0.55 mms ꢀ1 than that
of 2 (DEQ = 1.24 mmsꢀ1).[4b] Their large quadrupole splittings
may reflect a large electric-field gradient resulting from an
=
Fe O unit that is perpendicular to a tetradentate N4 donor set
that occupies the xy plane, of which 2 and 3 represent the only
examples thus far with neutral ligands. For comparison,
oxoiron(IV) complexes of planar polyanionic macrocyclic
ligands [FeIV(O)(Cl8tpp)(thf)](Cl 8tpp = tetrakis(2,6-dichlor-
ophenyl)porphinato; thf = tetrahydrofuran) and [FeIV2O-
(taml)2]2ꢀ (taml = tetraamido macrocyclic ligand) have
DEQ values of 2.08[9] and 3.3 mmsꢀ1.[10] Correlation of the
Mössbauer data with the near-IR spectrum taken of the
The above points can be placed on a more quantitative
basis by the Hammett plots shown in Figure 3. Good linear
correlations are obtained with the standard Hammett sub-
[11]
stituent parameter sp
for the oxidations by 1, affording
small positive 1 values (1 = 0.42 for PhCH2OH and 1 = 0.56
for Ph2S). In contrast, the oxidations by 3 have 1 values that
are larger and negative (1 = ꢀ1.4 for PhCH2OH and 1 = ꢀ1.3
for Ph2S). The point corresponding to Ph2S oxidation by 3 in
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complexes investigated as a function of the axial ligand span a
15-fold range and increase in the order of X = triflate, acetate,
chloride, methanol, fluoride. Unfortunately, the observed
order could not be correlated with any property of the axial
=
ligand or of the corresponding Fe O complex, leading the
authors to suggest a multistep reaction mechanism with at
least two steps that are partially rate-determining.
In contrast, for our study of 3, it is clear that electron-
donating substituents on the axial PyO ligand enhance the
oxidative reactivity of the oxoiron(IV) complex. This behav-
ior is in agreement with comparisons of reactivity among
[FeIV(O)(tmc)(X)]complexes, whereby the replacement of
the neutral MeCN axial ligand in the parent complex with
=
anions enhances the ability of the Fe O unit to perform H-
atom abstraction as the basicity of the anion increases (i.e.,
trifluoroacetate < azide < thiolate).[17] This notion is also
consistent with the speculated role of the thiolate ligand in
cytochrome P450.[1] We emphasize that this study of 3
represents the first for which a Hammett correlation has
been established for an axial ligand effect on the reactivity of
Figure 3. Hammett plots for the oxidations of benzyl alcohol (circles)
and diphenyl sulfide (squares) by 1 (open) and 3 (filled) as a function
of the 4-substituent of the added pyridine N-oxide. s=standard
Hammett substituent parameter.
an FeIV O unit.
=
The contrasting effects of cis and trans ligands on
reactivity very likely derive from perturbations to the
=
electronic structure of the highly covalent Fe O
the presence of 4-MeO-PyO deviates from the linear corre-
lation in Figure 3 (bottom panel) and may indicate a change in
oxidation mechanism. To probe the likelihood of a mecha-
nistic change, we obtained kinetic isotope effect (KIE) data
for benzyl alcohol oxidation by 1 and 3 in the presence of 4-
MeO-PyO and 4-O2N-PyO. The KIE was 15 for 1, whereas it
was 5 for 3, independent of the PyO substituent. If there is a
difference in mechanism with the methoxy substituent, the
rate-determining H-atom abstraction step does not reveal it.
We thus cannot explain why the rate of Ph2S oxidation by 3 in
the presence of 4-MeO-PyO is lower than expected. How-
ever, the accumulated data clearly demonstrate that PyOs
moiety.[17–19] DFT calculations reported thus far describe the
=
Fe O bond as consisting of a s bond, derived mainly from the
overlap of the empty metal dz2 orbital and the oxygen
pz orbital, and a p bond due to the interactions between the
half-filled metal dxz and dyz orbitals and the oxygen
pp orbitals.[17–19] A ligand trans to the oxo group would exert
a larger effect since it can interact strongly with both ds and
dp orbitals and compete with the oxo group. In experimental
support of this notion, we note a parallel behavior in the
intensity of the 1s!3d pre-edge transition found in the X-ray
absorption spectra of these complexes. The intensity of this
transition is essentially unchanged for 1 at 25(1) units with
variation of the sixth ligand,[5c,20] but it changes from 18–
31 units in the case of 2 for axial ligands ranging from thiolate
to trifluoracetate.[21] Binding of thiolate results in a decrease
=
exert opposite effects on the reactivity of the Fe O unit
depending on whether the PyO ligand is coordinated cis or
=
trans to the Fe O unit.
=
Literature precedents with which to compare our data are
few. As found for 1, a small and positive 1 value (0.31) was
observed in the oxidation of benzyl alcohol by a series of
[RuIV(O)(bpy)2(P(C6H4-p-X)3)]2+ complexes (bpy = 2,2’-
bipyridyl) in which the phosphine ligand is coordinated cis
of the pre-edge peak intensity and a lengthening of the Fe O
bond from 1.65 Š in the parent MeCN complex to 1.70 Š,[21a]
suggesting a weakening of the Fe O bond upon coordination
of the more basic thiolate ligand. This change leads to a
dramatic increase in the H-atom abstraction reactivity of the
=
to the Ru O unit.[12] Electron-withdrawing substituents make
Fe O unit. Similarly, electron-donating substituents make the
=
=
the RuIV O moiety a better oxidant. Similarly, introduction of
[FeIV(O)(L8py2)(OPy-4-R)]2+ complex 10–20-fold more reac-
=
halogen substituents on the porphyrin periphery increases the
tive than with electron-withdrawing substituents.
[13]
reactivity of [FeIV(O)(porphyrin)]complexes.
Thus, a cis
In summary, we have demonstrated in this work that
=
ligand appears to exert its effect simply by modulating the
ligands cis and trans to the Fe O unit modulate its reactivity
=
Lewis acidity of the M O center.
in disparate ways, shedding light on the various strategies
available for tuning the oxidative properties of nonheme iron
oxygenases.
=
The effect of a trans ligand on an Fe O center has
attracted more attention because of its importance in tuning
the oxidative reactivity of various heme enzymes.[1] In fact,
many studies show that the reactivity of high-valent iron
porphyrin complexes is affected by the axial ligand,[14–16] but
there is only one systematic study that directly monitors the
kinetics of substrate oxidation by oxoiron(IV) complexes.[16]
In this study, the second-order rate constants for styrene
epoxidation by [FeIV(O)(tetramesitylporphyrin radical)(X)]
Received: September 14, 2007
Revised: December 12, 2007
Published online: January 31, 2009
Keywords: bioinorganic chemistry · high-valent compounds ·
.
iron–oxo complexes · ligand effects · oxidation
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