Hydrogen-bonding effects on the reactivity of [X-FeIII-O-Fe IV=O] (X = OH, F) complexes toward C-H bond cleavage

Article abstract of DOI:10.1021/ic3027896

Complexes 1-OH and 1-F are related complexes that share similar [X-Fe ^III-O-Fe^IV=O]³⁺ core structures with a total spin S of ¹/₂, which arises from antiferromagnetic coupling of an S = ⁵/₂ Fe^III-X site and an S = 2 Fe^IV=O site. EXAFS analysis shows that 1-F has a nearly linear Fe^III-O-Fe^IV core compared to that of 1-OH, which has an Fe-O-Fe angle of ～130 due to the presence of a hydrogen bond between the hydroxo and oxo groups. Both complexes are at least 1000-fold more reactive at C-H bond cleavage than 2, a related complex with a [OH-Fe^IV-O-Fe ^IV=O]⁴⁺ core having individual S = 1 Fe^IV units. Interestingly, 1-F is 10-fold more reactive than 1-OH. This raises an interesting question about what gives rise to the reactivity difference. DFT calculations comparing 1-OH and 1-F strongly suggest that the H-bond in 1-OH does not significantly change the electrophilicity of the reactive Fe ^IV=O unit and that the lower reactivity of 1-OH arises from the additional activation barrier required to break its H-bond in the course of H-atom transfer by the oxoiron(IV) moiety.

Full text of DOI:10.1021/ic3027896

Article
pubs.acs.org/IC
Hydrogen-Bonding Effects on the Reactivity of [X−FeIII−O−FeIVO]
(X = OH, F) Complexes toward C−H Bond Cleavage
Genqiang Xue,† Caiyun Geng,‡ Shengfa Ye,*,‡ Adam T. Fiedler,† Frank Neese,*,‡
and Lawrence Que, Jr.*,†
†Department of Chemistry and Center for Metals in Biocatalysis, University of Minnesota, 207 Pleasant St. SE, Minneapolis,
Minnesota 55455, United States
‡Max-Planck Institut fur Chemische Energiekonversion, Stiftstr. 34-36, D-45470 Mulheim an der Ruhr, Germany
̈
̈
S
* Supporting Information
ABSTRACT: Complexes 1−OH and 1−F are related complexes that share similar
1
[X−FeIII−O−FeIVO]3+ core structures with a total spin S of /2, which arises from
antiferromagnetic coupling of an S = 5/2 FeIII−X site and an S = 2 FeIVO site. EXAFS
analysis shows that 1−F has a nearly linear FeIII−O−FeIV core compared to that of 1−
OH, which has an Fe−O−Fe angle of ∼130° due to the presence of a hydrogen bond
between the hydroxo and oxo groups. Both complexes are at least 1000-fold more
reactive at C−H bond cleavage than 2, a related complex with a [OH−FeIV−O−FeIV
O]4+ core having individual S = 1 FeIV units. Interestingly, 1−F is 10-fold more reactive
than 1−OH. This raises an interesting question about what gives rise to the reactivity
difference. DFT calculations comparing 1−OH and 1−F strongly suggest that the H-
bond in 1−OH does not significantly change the electrophilicity of the reactive FeIV
O unit and that the lower reactivity of 1−OH arises from the additional activation
barrier required to break its H-bond in the course of H-atom transfer by the
oxoiron(IV) moiety.
In our effort to obtain synthetic analogs of such high-valent
diiron species, we have characterized the first examples of
complexes with [FeIIIFeIV(μ-O)2]23 (1 in Scheme 1) and
INTRODUCTION
■
Nonheme diiron enzymes catalyze the activation of dioxygen to
cleave the C−H bonds of a variety of substrates. This class
includes soluble methane monooxygenase (sMMO), related
bacterial multicomponent monooxygenases, and fatty acid
desaturases.1−6 High-valent intermediates are implicated in
the oxygen activation mechanisms for these enzymes.3,5−7 For
example, intermediate Q of sMMO is a two-electron oxidant
that effects the hydroxylation of methane8−14 and has been
proposed to have an [FeIV2(μ-O)2] diamond core on the basis
of extended X-ray absorption fine structure (EXAFS) studies.15
Related diiron(IV) oxidants may also be involved in the
catalytic cycles of fatty acid desaturases and other diiron
monooxygenases resulting from cleavage of the O−O bond in
observed peroxo intermediates,16−18 but direct evidence for
such diiron(IV) species has not yet been obtained. Similar
oxygen activation chemistry is utilized by ribonucleotide
reductases (RNR) with diiron and iron−manganese centers,
which generate an intermediate called X that is used for the
one-electron oxidation of a specific Cys residue that is needed
to initiate the deoxygenation of ribonucleotides to deoxy-
ribonucleotides.19 For these enzymes, FeIII−O−MIV (M = Fe or
Mn) oxidants have been trapped,20−22 and the best structurally
characterized one is the intermediate for the RNR from
Chlamydia tranchomatis, which has been shown to have an
[FeIIIMnIV(μ-O)(μ-OH)] diamond core on the basis of Fe and
Mn K-edge EXAFS experiments and associated density
functional theory (DFT) calculations.22
Scheme 1. Structures of High-Valent Diiron Complexes in
This Study
Received: December 19, 2012
© XXXX American Chemical Society
A
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[FeIV2(μ-O)2]24 core structures, providing synthetic precedents
for the [FeIV2(μ-O)2] core proposed for Q.15 More recently, we
reported the generation of 1−OH, a complex with an open
HO−FeIII−O−FeIVO core structure, by the addition of
hydroxide to 1 or by the one-electron reduction of its HO−
FeIV−O−FeIVO precursor 2 (Scheme 1).25 As EXAFS
characterization of 2 shows an Fe−Fe distance of 3.32 Å and
an Fe−O−Fe angle of 130°, it is clear that the Fe−O−Fe unit is
bent,26 implicating a hydrogen-bonding interaction between the
hydroxo proton on one Fe to the oxo on the other Fe. By
extension, 1−OH is also proposed to have such an H-bond.
Indeed, direct spectroscopic evidence for the hydrogen bond in
1−OH has recently been obtained by 1H-ENDOR experi-
ments.27
In this paper, we compare the reactivities of 1−OH and 1−F,
another open-core complex derived from the addition of F− to
1, and find that 1−F is an order of magnitude more reactive
than 1−OH in H-atom abstraction. Unlike the hydroxo ligand
in 1−OH, the iron(III)-bound fluoride should not be capable
of hydrogen bonding to the terminal FeIVO unit, so the
difference in reactivity may be related to the presence of the
hydrogen bond. Indeed, EXAFS analysis establishes the
presence of a linear Fe−O−Fe unit in 1−F. DFT calculations
have been carried out on both 1−OH and 1−F to shed further
light on this reactivity behavior.
Figure 1. UV−vis spectra of complexes 1 (green line, 0.2 mM) and 1−
F (red line) obtained upon addition of Bu4NF to the solution of 1.
Additional gray lines show the spectroscopic changes during the
reaction of 1−F with 2.0 mM DHA until the reaction is complete
(black line). Inset: time trace at 420 nm (black solid line) together
with the fit (red dashed line) using a first-order model. Conditions: in
3:1 CH2Cl2−MeCN under Ar at −80 °C.
solution contained 3 mM of diiron species in 3:1 PrCN−MeCN, with
75% yield (2.2 mM) of 1−F based on Mossbauer analysis. The energy
̈
EXPERIMENTAL AND COMPUTATIONAL DETAILS
range was 6.9−8.0 keV. The monochromator was calibrated using the
K-edge energy of iron foil at 7112.0 eV. The program EXAFSPAK31
was used for evaluation of the data and for EXAFS fitting, the latter in
conjunction with FEFF 8.32 SSExafs33,34 was used for fitting of the pre-
edge region of XAS spectra.
■
Complexes 1 and 2 were prepared according to reported
procedures.24,26 9,10-Dihydroanthracene (DHA, 97%), fluorene
(>99%), and ferrocene (Fc, 98%) purchased from Aldrich were
recrystallized (from EtOH for the former two and MeOH for the latter
one) prior to use. Butyronitrile (PrCN, 99%+) purchased from Aldrich
was purified and dried according to reported procedures.28 9,9,10,10-
d4-DHA was synthesized according to reported procedures.25
Tetrabutylammonium fluoride hydrate (Bu4NF·xH2O) purchased
from Aldrich (98%) was dried under vacuum at 40 °C.29 Anhydrous
dichloromethane (>99.8%) and acetonitrile (>99.8%) purchased from
Aldrich were used without further treatment. Bu4NOCD3 was
prepared according to reported procedures.30 UV−vis spectra and
kinetic time traces were recorded on a Hewlett-Packard 8453A diode
array spectrometer equipped with a cryostat from Unisoku Scientific
Instruments, Osaka, Japan. This combination allows kinetic studies to
be performed at temperatures down to −85 °C and to record a
spectrum (in the range of 190−1100 nm) every 0.1 s. For some rapid
reactions with a reaction time of 10 s, time traces at one wavelength
can be obtained with about 100 data points for reliable kinetic fits (see
Figure 1). 31P NMR data were collected on a Varian VXR-300
spectrometer.
Computational Studies. All calculations were performed with the
ORCA program package.35 For geometry optimizations, the pure
BP8636 and hybrid B3LYP density functionals37,38 in combination with
triple-ζquality basis sets (TZVP)39 for key surrounding atoms involved
in C−H bond activation and SVP basis sets40 for the remaining atoms
were used throughout the study. The resolution of the identity41−43
(RI, for BP86) and RI plus chain of spheres44 (RIJCOSX, for B3LYP)
approximations were used to accelerate the calculations using the
auxiliary basis set SV/J.42 All the geometries were fully optimized
without symmetry constraints. Harmonic vibrational frequencies were
computed by two-sided numerical differentiation of analytic gradients
to verify the nature of the stationary points. The minimum structures
reported in this paper have only positive eigenvalues of the Hessian
matrix, whereas the transition states (TSs) have only one negative
eigenvalue. The zero-point energies, thermal corrections, and entropy
terms for the optimized geometries were obtained from the frequency
calculations.
In order to obtain single-point energies closer to the basis set limit,
B3LYP calculations with the much larger def2-TZVPP basis set45 on
all elements were carried out. The energies reported in this paper refer
to these calculations.
Solvent effects are taken into account via the conductor-like screen
model (COSMO) for all calculations. Acetonitrile (ε = 36.6) was
chosen as the solvent. To consider dispersion forces, geometry
optimizations and single point calculations were also undertaken
included semiempirical van der Waals (VDW) corrections.46−48
Reactivity Studies. All reactivity measurements were performed in
a 3:1 mixture of CH2Cl2−MeCN under Ar to allow measurements to
be made at −85 °C. A solution of 1−F was prepared by addition of 1.5
equiv of Bu4NF to 1 (typically 0.2 mM), while a solution of 1−OH
was prepared by reduction of 2 (typically 0.2 mM) with 1 equiv of
ferrocene. For a typical reactivity experiment, an appropriate amount
of substrate (from a stock solution in CH2Cl2) was introduced to the
solution of the complex via a micro syringe, and the reaction solution
was monitored by UV−vis spectroscopy. The pseudo-first-order rate
constants kobs were obtained by fitting the decay time traces, and the
second-order rate constants k2 were obtained by fitting the kobs versus
substrate-concentration plots. The reaction solutions were filtered
through silica gel columns to remove iron complexes prior to product
analyses. The yield of the anthracene product from DHA oxidation
was quantified by the absorbance of the filtrates at 377 nm (ε = 7700
M−1 cm−1).
RESULTS AND DISCUSSION
■
Comparing the Reactivities of 1−F and 1−OH. As
shown in Figure 1, addition of 1.5 equiv of Bu4NF to a solution
of 1 at −80 °C causes decay of its 620 nm chromophore (green
line) and its complete conversion to a new species with λmax at
about 400 nm (red line), which is characteristic of 1−F.49
Subsequent addition of 9,10-dihydroanthracene (DHA) to this
mixture speeds up the decay of the 400-nm chromophore and
XAS Study. Fe K-edge X-ray absorption spectra (XAS, fluorescence
excitation, Ge detector) of a frozen solution of 1−F were recorded at
∼10 K at the Stanford Synchrotron Radiation Laboratory (SSRL). The
B
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forms near-UV absorption features characteristic of the
anthracene product at 377 and 357 nm (black line). The
anthracene yield is 35% with respect to 1 (and ∼50% with
respect to 1−F, based on its ∼75% yield relative to 1 that has
transfer (HAT) is the major component of the rate-
determining step in DHA oxidation by 1−F and 1−OH.
However, 1−F oxidizes DHA about 10-fold faster than 1−OH
at −80 °C (see Table 1). The same difference in rates was
been estimated by Mossbauer analysis49). The resulting
̈
Table 1. Comparison of Second-Order Rate Constants (M−1
s−1) for C−H Bond Cleavage Reactions of High-Valent
Diiron Complexes
solution is EPR silent, suggesting that a diiron(III) product is
formed. Taken together, these results suggest that 1−F
effectively acts as a one-electron oxidant in DHA oxidation.
There is an isosbestic point at about 380 nm in the course of
DHA oxidation, suggesting that this is a simple A-to-B reaction
and no intermediate is involved. (In Figure 1, note that the red
line, corresponding to the spectrum of 1−F right after Bu4NF
addition, does not cross this isosbestic point, because
subsequent addition of substrate solution results in sample
dilution and a baseline shift. This perturbation is also indicated
by the bump at the beginning of the absorption time trace
shown in the inset of Figure 1.)
The progress of DHA oxidation can be monitored by
following the decay of the absorption at 420 nm, and the time
traces can be fit with a pseudo-first-order model to obtain kobs
values (Figure 1, inset). As 1−F are a one-electron oxidant, 2
equiv of 1−F are required to oxidize one molecule of DHA.
Thus, pseudo-first-order conditions can be achieved even with a
substrate/1−F ratio of 5, as less than 10% of the added
substrate will have been consumed at the end of the reaction.
Indeed, excellent fits to a first-order decay were obtained for all
experiments represented in Figure 2. (We were constrained to
DHA (−80 °C)
3.2(2) × 102
DHA (−85 °C) fluorene (−80 °C)
1−F
1.8(1) × 102
65(1)
KIE = 40
a
1−OH
28(1)
13(1)
6.5(5)
a
KIE = 50
b
1−OCD3
3.6 × 102
a
2
2.7 × 10−2
KIE = 30 (−30 °C)
a
b
From ref 25. From ref 30.
observed at −85 °C (Figure S1, Supporting Information).
Similar reactivity differences are also observed for fluorene,
another hydrocarbon substrate with a stronger C−H bond
(BDE = 80 vs 78 kcal/mol for DHA;50 Table 1 and Figure S2,
Supporting Information). Under the same conditions, the
reactivity of 1−F is quite comparable to that of 1−OCD3
(Table 1), a recently reported complex with a [CD3O−FeIII−
O−FeIVO]3+ core structure.30
Activation Parameters for DHA Oxidation by 1−OH.
Figure 3 shows the Eyring plot for DHA oxidation by 1−OH in
Figure 2. Plots of kobs vs [substrate] for the oxidation of DHA
(squares) and DHA-d4 (circles) by 1−F, with k2 of 3.2(2) × 102 and
8.2(1) M−1 s−1, respectively. Conditions: in 3:1 CH2Cl2−MeCN under
Ar at −80 °C. With one exception, all reactions were carried out with
1−F generated from 0.2 mM 1. For the data point corresponding to
0.5 mM DHA, 0.1 mM 1 was used to generate 1−F to maintain
pseudo-first-order conditions. Experimental constraints on our ability
to measure the high rate of the DHA reaction limited how high a DHA
concentration could be used.
Figure 3. Eyring plot for DHA oxidation by 1−OH in 3:1 CH2Cl2−
MeCN under Ar. ΔH⧧ = 5.1(4) kcal mol−1 and ΔS⧧ = −26(2) cal
mol−1 K−1. The k2 values at different temperatures are listed in Table
S1 (Supporting Information).
the temperature range of −85 to −40 °C. The activation
parameters calculated from the plot are ΔH⧧ = 5.1(4) kcal
mol−1 and ΔS⧧ = −26(2) cal mol−1 K−1. For comparison, the
temperature dependence of the intramolecular oxidation of the
OCH3 group in 1−OCH3 afforded Eyring parameters of ΔH⧧
= 9.7 kcal mol−1 and ΔS⧧ = −15 cal mol−1 K−1.30 The smaller
ΔH⧧ value for DHA oxidation by 1−OH reflects the lower
activation barrier for cleaving the significantly weaker C−H
bond of DHA, while its more negative ΔS⧧ value is consistent
with the intermolecular nature of the reaction. Unfortunately,
the activation parameters for the reaction of 1−F with DHA
could not be determined for comparison with those of 1−OH,
use DHA concentrations of 2.0 mM or less, because the
oxidation rate was too fast for higher DHA concentrations to be
accurately measured by our UV−vis spectrometer.) The
second-order rate constant (k2) can then be obtained from
the slope of the linear kobs−[substrate] plot (Figure 2).
The reaction of 1−F with DHA slows down significantly
when 9,9,10,10-d4-dihydroanthracene (DHA-d4) is used as the
substrate (Figure 2). The kinetic isotope effect (KIE) value of
40 at −80 °C is comparable to that observed for 1−OH (50
under the same conditions)25 and confirms that hydrogen atom
C
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because the reactions at higher temperature were too fast for us
to measure.
XAS Characterization of 1−F. The geometric structure of
1−F has been examined with X-ray absorption spectroscopy
(XAS). As shown in Figure 4, the first derivative of the XAS
Figure 5. Fourier transform of Fe K-edge data (dashed line) for a 2.1
mM solution of 1−F in 3:1 PrCN−MeCN obtained at 10 K. Fourier-
transform range: k = 2.1−14.5 Å−1. The best fit (solid line) was
obtained with the following parameters: 0.5 O/N at 1.66 Å (Δσ2,
0.0084), 1.5 O/N at 1.83 Å (0.0049), 1 N/O at 2.04 Å (0.0012), 3 N/
O at 2.17 (0.0021), 6.5 C at 3.04 Å (0.0085), and 1 Fe at 3.56 Å
(0.0037). The fit also included a multiple-scattering feature arising
from the nearly linear Fe−O−Fe unit.
Figure 4. Black line: X-ray absorption near-edge structure (XANES) of
1−F (2.1 mM) in 3:1 PrCN−MeCN. Left inset: pre-edge features
observed between 7100 and 7120 eV. Right inset (red dashed line):
first derivative of the XAS spectrum in the 7100−7140 eV region. Two
distinct edge energies are observed at E0 = 7124.8 and 7128.6 eV.
Information). This discrepancy was likely due to neglect of
multiple-scattering effects in our first-order analysis, as multiple-
scattering effects amplify the intensity of the distant scatterer in
a linear triatomic array,55 such as the Fe−O−Fe unit in 1−F.
Thus, the FEFF program was used to account for multiple-
scattering intensity arising from the Fe−O−Fe unit. Our initial
model, depicted in Figure S4 (Supporting Information),
assumed six-coordinate metal centers with iron−ligand
distances largely derived from our first-order EXAFS analysis.
However, on the basis of insights into the structure of 1−F
from other methods, the first shell was split into two
components: (i) an O scatterer at 1.65 Å (0.5 occupancy),
corresponding to the terminal oxo ligand of the iron(IV)
center, and (ii) an O/F scatterer at 1.80 Å (1.5 occupancy),
corresponding to the fluoride ligand of the iron(III) ion and the
μ-oxo group. As shown in Figure S5 (Supporting Information),
the FEFF-calculated FT from this model nicely matches the
experimental data, suggesting that multiple-scattering effects
indeed make significant contributions to the EXAFS data. The
distances and Debye−Waller factors (Δσ2) of all the scatterers
derived from either single scattering or multiple scattering
mechanisms were then allowed to vary (with certain
constraints) to improve the correspondence between the
experimental and computed data. This procedure yielded a
high-quality fit that accounts for all salient experimental
features, including the intensity of the Fe scatterer peak in
the FT [Figure 5; see Figure S6 (Supporting Information) for
the fit of the EXAFS data prior to Fourier transformation].
Although most of the first-sphere bonds lengths were relatively
unchanged, this second-order approach resulted in a modest
shortening of the Fe···Fe distance from 3.64 to 3.56 Å. As
complexes with linear FeIII−O−FeIII units typically have Fe···Fe
distances of 3.6 Å,23,56,57 the somewhat shorter Fe···Fe distance
observed for 1−F probably reflects the expected contraction of
the FeIV−μ-O bond length.58 In contrast, the EXAFS analysis of
2, the one-electron-oxidized diiron(IV) analog of 1−OH, has
revealed an Fe···Fe distance of 3.32 Å,26 which is 0.24 Å shorter
than that of 1−F and corresponds to an Fe−O−Fe angle of
intensity reveals two distinct edge energies at E0 = 7124.8 and
7128.6 eV, similar to what is found for its precursor 1 at 7124.8
and 7129.4 eV.24 The pre-edge region can be fit with three
discernible features at 7113.8, 7115.5, and 7117.1 eV (Table S2,
Supporting Information), which are found at energies almost
identical to those observed for synthetic mononuclear high-spin
oxoiron(IV) complexes51,52 and provide further support for the
assignment of an S = 2 spin state for the oxoiron(IV) moiety in
1−F. These pre-edge features have a total area of 24.8 units,
which is within the range of values found for the synthetic
mononuclear high-spin oxoiron(IV) complexes.51,52 The
features associated with the six-coordinate high-spin iron(III)
center of 1−F are expected to be much less intense53,54 and
would thus be obscured by the more intense bands of the high-
spin oxoiron(IV) unit.
The Fourier transform (FT, r′-space) of the Fe K-edge
EXAFS data collected for 1−F is shown in Figure 5. It displays
intense features at r′ = 1.7 and 3.2 Å, along with two smaller
peaks in between (r′ = r − ρ, where r is the actual metal-
scatterer distance and ρ is a phase shift of ∼0.4 Å). Initial
analysis of the EXAFS data assumed that these spectral
contributions were derived entirely from single-scattering
mechanisms. The best fit obtained with this approach included
three first-sphere shells at 1.80, 2.07, and 2.18 Å, each
consisting of two O/N atoms. The shells with r > 2 Å
correspond to the N atoms of ligand L, while the 1.80 Å shell is
a conglomeration of the fluoride, terminal oxo, and bridging
oxo ligands. Fitting of the second-sphere features required six C
scatterers at 2.99 Å (standard for high-valent complexes with
the tris(2-pyridylmethyl)amine-type (TPA) ligands24) and an
Fe scatterer at 3.64 Å.
While the single-scattering fit is satisfactory, it does not
accurately reproduce the unusually high intensity of the Fe
scatterer peak at 3.2 Å in the FT (Figure S3, Supporting
D
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130°. These geometric differences are proposed to result from
the presence of an H-bond between the FeIV−O−H and the
FeIVO units. A similar Fe···Fe distance and a comparable
Fe−O−Fe angle are observed in the crystal structure of a
[H2O−FeIII−O−FeIII−OH] complex with a related 5-ethyl-
substituted TPA supporting ligand, where H-bonding is
observed between the OH− and H2O ligands.23 The
r(Ohydroxo−Ooxo) of 2.46 Å in 2 predicted from DFT geometry
optimization26 is also very similar to that of the diferric complex
(2.464 Å),23 further supporting the presence of the H-bond.
We speculate that the H-bond remains upon one-electron
reduction of 2 to form 1−OH. This speculation is supported by
the fact that irradiation of a frozen solution of 2 at 77 K with
60Co, conditions under which only electron transfer can occur
and no structural change is possible, also generates 1−OH.49
As previously determined by Mossbauer spectroscopy,49 the
̈
1−F sample prepared for spectroscopic studies consists of
about 75% 1−F with 22% associated with the diiron(III) decay
product. The high fraction of 1−F in the XAS sample is
supported by the presence of relatively intense pre-edge
features associated with a high-spin oxoiron(IV) unit (see
discussion above). While the diiron(III) decay product in the
sample could potentially affect the EXAFS results, its presence
is unlikely to alter the two major conclusions of our analysis: (i)
the presence of a scatterer at 1.66 Å arising from an FeIVO
unit and (ii) the Fe−Fe bond distance of 3.56 Å. Regarding the
scatterer at 1.66 Å, the diiron(III) contaminant would not
possess such a short Fe−O bond, so we are confident that this
feature arises from 1−F. With respect to the Fe−Fe distance, it
is likely that the diiron(III) contaminant would also have a
linear Fe−O−Fe unit and could thus contribute to the
observed Fe scatterer at 3.56 Å. However, given that it only
represents 22% of the sample, it is highly unlikely that the decay
product would solely be responsible for the intense Fe
contribution at 3.56 Å. In the best fit, the Fe scatterer has an
N value of 1.0 and a reasonable Δσ2 value of 0.0037. If we
assume that the decay product alone gave rise to the observed
Fe scatterer, the N value would have to be decreased to 0.22
and the associated Δσ2 value would become unreasonably small
or perhaps even negative in value. Lastly, we emphasize that the
EXAFS data can be well simulated using a DFT model of 1−F
(Figure S5, Supporting Information).
DFT Calculations. DFT calculations were performed on 1−
OH and 1−F in both syn and anti conformations, as shown in
Figure 6. For the syn conformer 1−OHsyn, the oxo and hydroxo
groups are linked by hydrogen bonding, which enforces an Fe−
O−Fe angle about 130°. Documented below are the results
obtained with B3LYP functionals; very similar results were
obtained with BP86 functionals, which are presented in Table
S3 (Supporting Information). The optimized structure of 1−
OHsyn (shown in Figure 6) features an open [HO−FeIII−O−
FeIVO]2+ core structure, similar to that of its one-electron-
oxidized diiron(IV) analog.26 The calculated O1−H1 bond
distance (1.78 Å) and the O1···O3 separation (2.73 Å) clearly
indicate the presence of a weak hydrogen bond between the
terminal oxo and hydroxyl groups, consistent with the van der
Waals radii of the H- (1.20 Å) and O-atoms (1.52 Å).59
Formation of the hydrogen bond is facilitated by the proximity
of the FeO and Fe−OH units. Consequently, 1−OHsyn has a
relatively short Fe−Fe distance of 3.34 Å and a bent Fe1−O2−
Fe2 angle of 131.9°. For comparison, 1−OHanti is only about
2.4 kcal/mol higher in energy than 1−OHsyn, reflecting that the
H-bond strength in 1−OHsyn is rather weak. Due to the loss of
Figure 6. Optimized core structures of 1−OH and 1−F. Bond lengths
are in angstroms and angles in degrees. Atom color scheme: H, white;
O, red; Fe, orange; F, green.
the H-bond, 1−OHanti adopts a nearly linear Fe1O2Fe2
arrangement with an Fe−O−Fe angle of 174.5° and a longer
Fe···Fe distance of 3.62 Å. The results of these calculations are
fully consistent with the earlier DFT results of De Hont et al.49
(Figure S7, Supporting Information) and with recent 1H-
ENDOR data that provides direct spectroscopic evidence of the
H-bond.27
Like 1−OH, two conformations were taken into account for
1−F computationally, and both conformers represent local
minima in the calculations. However, the hypothetical syn
conformer 1−Fsyn, which most closely resembles 1−OHsyn, is
computed to be 5.2 kcal/mol higher in energy than the anti
conformer, 1−Fanti. Thus, in agreement with experiment, the
calculations confirm that the anti configuration is energetically
more favored. Our calculated key geometric parameters for 1−
Fanti agree with the results from previous DFT calculations
(Figure S7, Supporting Information)49 and match the
experimental EXAFS data (Figure 5) reasonably well. For
both conformers, the calculated FeIV−oxo bond length of 1.64
Å is comparable to those found for 1−OHsyn (1.66 Å) and 1−
OHanti (1.65 Å). 1−Fanti features a linear Fe1O2Fe2 arrangement
with a long Fe1···Fe2 distance of 3.57 Å, similar to that
calculated for 1−OHanti. The absence of the hydrogen bond in
1−Fsyn results in a loose “pocket”, as evidenced by the rather
long F···O1 separation (2.99 Å) and the slightly larger Fe1−
O2−Fe2 angle (135.2°) compared to that of 1−OHsyn. In
analogy to 1−OHsyn, 1−Fsyn possesses a bent Fe1O2Fe2 core
and hence displays a shorter Fe1···Fe2 distance relative to 1−
Fanti (Figure 6).
As shown in Table 1, 1−Fanti is found to be 10-fold faster
than 1−OHsyn in cleaving C−H bonds, which in turn is 1000-
fold faster than 2, its one-electron-oxidized form.25 To gain
insight into the factors that may contribute to this difference,
the reactivities of 1−OHsyn and 1−Fanti were theoretically
modeled, focusing on the rate-determining H-atom abstraction
step. Table 2 lists selected structural parameters from the
B3LYP-optimized geometries, and Figure 7 shows the Gibbs
free energy profiles for DHA C−H bond activation by 1−OHsyn
and 1−Fanti
.
60 As shown in Figure 7 and Figure S8 (Supporting
E
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Table 2. Selected Geometric Parameters Obtained from the Calculations Including VDW Corrections for the Key Points along
a
the Reaction Pathways
r(Fe1−O1)
r(Fe1−Fe2)
∠Fe1O2Fe2 (deg)
∠O1Fe1Fe2X (deg)
r(O1−O3)
r(O1−H1)
r(O1−H2)
r(C−H2)
RC(1−OHsyn
TSH(1−OHsyn
IN(1−OHsyn
RC(1−Fanti
TSH(1−Fanti
IN(1−Fanti
RC(1−OHanti
TSH(1−OHanti
IN(1−OHanti
)
1.66 (1.66)
1.73 (1.75)
1.88 (1.89)
1.64 (1.64)
1.72 (1.73)
1.86 (1.88)
1.65 (1.65)
1.72 (1.73)
1.88 (1.87)
3.34 (3.37)
3.33 (3.38)
3.33 (3.39)
3.49 (3.54)
3.59 (3.63)
3.60 (3.62)
3.54 (3.60)
3.59 (3.64)
3.63 (3.64)
133.34 (134.04)
131.90 (134.31)
132.25 (135.71)
152.69 (156.80)
172.79 (175.92)
167.86 (166.38)
163.41 (166.68)
176.02 (178.25)
174.06 (174.13)
2.59 (0.02)
2.73 (2.74)
1.79 (1.80)
−
1.10 (1.10)
1.20 (1.21)
2.41 (2.59)
1.10 (1.10)
1.20 (1.20)
2.51 (3.12)
1.10 (1.10)
1.21 (1.22)
2.58 (3.04)
)
−5.55 (−15.53)
1.42 (0.96)
2.77 (2.84)
1.82 (1.89)
1.40 (1.40)
0.96 (0.96)
2.31 (2.42)
1.39 (1.41)
0.96 (0.96)
2.10 (2.50)
1.38 (1.40)
0.96 (0.96)
)
2.75 (2.79)
1.80 (1.84)
)
−134.62 (−135.03)
173.44 (172.99)
175.29 (170.65)
−145.95 (−143.79)
−172.54 (172.92)
−178.27 (178.94)
−
−
−
−
−
−
−
−
−
−
−
−
)
)
)
)
)
a
Values without VDW corrections are given in parentheses.
in the calculated entropy contribution to the free energy (>10
kcal/mol) for a given combination reaction, especially in
solution,62,63 i.e., approach of the substrate toward the reactive
center in the present case, we chose the reaction complex (RC),
where the substrate weakly bonds to the FeIVO site, as the
reference point to calculate the reaction barrier. With this
caveat, the direct comparison of the computed activation
barrier with the experimental data requires more caution.
In fact, the process of C−H bond oxidation by the two
complexes follows the same reaction mechanism. As expected,
the reaction takes place at the FeIVO unit and proceeds by
the σ-mechanism that has been well-established for S = 2
mononuclear oxoiron(IV) complexes.64−68 In the σ-pathway of
C−H bond activation by a high-spin FeIVO center, one
electron from the substrate that has the same spin as the
remaining electrons in the FeIV center is transferred into the
σ*(FeO) antibonding orbital (Scheme 2). During this
process, the oxidation state of the diiron core changes from a
mixed valence FeIII−FeIV state in the RCs to an FeIII−FeIII state
in the transition states (TSH) and the intermediates (IN). As
the two complexes are supported by the same ligand and, more
importantly, share similar open core [X−FeIII−O−FeIVO]3+
structures, the main question is why 1−Fanti exhibits a stronger
oxidizing ability than 1−OHsyn.
Figure 7. Calculated schematic Gibbs free energy (ΔG) surfaces for
the cleavage of the C−H bond of DHA by 1−OHsyn (blue line), 1−
Fanti (red line), and 1−OHanti (black line). Energies without VDW
corrections are given in parentheses.
We considered several factors that could account for the
increase in reactivity upon going from 1−OHsyn to 1−Fanti. The
first factor might be the changes in the electronic properties of
the FeIVO reactive center that is directly involved in the
reaction. As shown in Table 2, the estimated FeO bond
Information), the energy barrier for H-atom abstraction by 1−
OHsyn is calculated to be 3.3 kcal/mol at the B3LYP+VDW
level of theory, 0.8 kcal/mol higher than that calculated for 1−
Fanti (2.5 kcal/mol). This barrier difference corresponds to a
ratio of 6 between the reaction rates for 1−Fanti and 1−OHsyn,
in good agreement with the 10-fold rate enhancement observed
experimentally. This factor increases to 7, when the hydrogen-
tunneling correction due to Wigner61 is included. The DFT
results nicely reproduce the experimental findings, although the
calculations without VDW corrections may slightly over-
estimate the barrier difference. Because there is a large error
distance in 1−OHsyn is marginally longer than that in 1−Fanti
.
Moreover, the calculated FeO bond order of 1.7 for 1−OHsyn
is slightly lower than that for 1−Fanti (1.8), which is consistent
with the computed FeO stretching frequencies (834 cm−1 for
1−OHsyn vs 867 cm−1 for 1−Fanti). (Unfortunately, we were
unsuccessful in our attempt to obtain resonance Raman data for
Scheme 2
F
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Inorganic Chemistry
Article
these complexes that could have experimentally substantiated
these calculated changes.) Therefore, the hydrogen bond does
not noticeably change the bonding properties of the FeIVO
motif in 1−OHsyn. As such, one may predict that the FeIVO
sites in 1−OHsyn and 1−Fanti would exhibit similar reactivity. In
line with this reasoning, nearly identical Fe1−O1, C−H2, and
O1−H2 bond distances were found in TSH(1−OHsyn) and
TSH(1−Fanti) (Table 2).
FeIVO unit along the reaction coordinate. As discussed
elsewhere, as the FeO bond lengthens, the FeIVO
intermediate evolves to a species that is best characterized as
FeIII−oxyl.64,71 The lengthening of the hydrogen bond (O1−
H1) in TSH(1−OHsyn) reflects the fact that the oxyl group has
lower electron-donating capability relative to the more
negatively charged oxo ligand. Thus, the larger geometric
distortion resulting from this additional reaction coordinate
leads to a higher barrier for the reaction with 1−OHsyn
compared to 1−Fanti. To corroborate this notion, we have
theoretically investigated the same reaction with the anti
conformer 1−OHanti. It turns out that 1−OHanti is more
efficient in C−H bond activation than 1−OHsyn and 1−Fanti
(Figure 7), although the computed Fe1−O1 and C−H2
distances in TSH(1−OHanti) are almost the same as those
found for 1−OHsyn and 1−Fanti (Table 2). This indicates that
partially breaking the hydrogen bond indeed slows down the
reaction for 1−OHsyn and explains the higher energy barrier
encountered by 1−OHsyn than that for 1−Fanti. The difference
in reactivity between the two anti conformers mainly originates
from the larger geometry reorganization required for the
reaction with 1−Fanti relative to 1−OHanti upon going from RC
to TSH, as indicated by geometric parameters such as the Fe1−
Fe2 distances, the Fe1−O1−Fe2 angles, and the O1−Fe1−Fe2−X
dihedral angles (Table 2). Our calculations show that the
change in the reorganization energies gives ∼1 kcal/mol
difference in the reaction barriers.
The second factor for the increased reactivity of 1−Fanti over
1−OHsyn could be the different steric barriers encountered in
the two systems. In fact, as shown in Figure 8, the reaction
Taken together, our calculations reveal that the hydrogen
bond between the oxo and hydroxo group in 1−OHsyn does not
significantly change the bonding properties of the FeIVO unit
and hence its reactivity. However, during the reaction of C−H
bond oxidation, this hydrogen bond has to be partially broken.
This leads to the slightly higher barrier for 1−OHsyn relative to
1−Fanti, which has a similar open-core structure but no
hydrogen bond.
Figure 8. Space-filling models of reaction complexes (RCs) and
transition states (TSHs) for 1−Fanti, 1−OHsyn, and 1−OHanti. Atom
color scheme: C, gray; H, white; N, blue; O, red; Fe, orange; F, green.
CONCLUDING REMARKS
■
Complexes 1−OH and 1−F are related complexes that are
supported by the same tetradentate tripodal ligand and, more
importantly, share similar [X−FeIII−O−FeIVO]3+ core
structures. They both have a high-spin (S = 2) terminal
center (terminal oxo) in 1−Fanti is partially shielded by the
pyridine group that is oriented syn with respect to the terminal
oxo group. Therefore, it is easier for the substrate to approach
the reactive center in 1−OHsyn than in 1−Fanti. Consequently,
we would expect higher reactivity of 1−OHsyn compared to that
of 1−Fanti from such an analysis. However, experiment
demonstrated the opposite trend for the reactivity of the two
complexes. Thus, the underlying reason for this intriguing
reactivity difference must lie elsewhere.
In the H-atom abstraction process by mononuclear iron−oxo
complexes, the key reaction coordinates are the lengthening of
the target C−H bond of the substrate and the FeIVO bond of
the oxidant.67,69,70 Indeed, for the reaction with 1−Fanti, we
have not observed any other coordinates that undergo
significant changes en route to the transition state. Interestingly,
an additional reaction coordinate was identified in the reaction
with 1−OHsyn. This motion involves lengthening of the
hydrogen bond between the hydroxide and terminal oxo
groups. As shown in Table 2, comparison of the structures of
RC(1−OHsyn) and TSH(1−OHsyn) clearly demonstrates
weakening of the hydrogen bond during the reaction process,
especially for the calculations without VDW corrections. This is
readily ascribed to the changes in the electronic structure of the
FeIVO moiety based on EPR and Mossbauer analysis.30,49
̈
They are also much more reactive at cleaving C−H bonds than
2, the one-electron more oxidized precursor of 1−OH.
Complex 2 differs from 1−OH and 1−F in having an S = 1
FeIVO unit, which supports the DFT-derived hypothesis that
a high-spin oxoiron(IV) center is more reactive than an
intermediate-spin one due to exchange-enhanced reactivity. H-
atom abstraction by an S = 2 FeIVO unit would introduce an
2
α electron into the empty dz (σ*) orbital, leading to an increase
in the number of exchange interactions, while H-atom
abstraction by an S = 1 FeIVO unit would likely introduce
a β electron into a dxz/yz(π*) orbital, leading to a decrease in the
number of exchange interactions. This difference leads to a
much lower activation barrier for this key step of the reaction in
the case of the S = 2 FeIVO unit.
Interestingly, the C−H bond cleavage reactivity of 1−F is 10-
fold higher than that of 1−OH. On the basis of DFT
calculations, we attribute this reactivity difference to the distinct
core structures of 1−F and 1−OH. In conjunction with an
earlier DFT study,49 a recent ENDOR study experimentally
demonstrated that there is a hydrogen bond between the FeIII−
OH and the FeIVO units of 1−OH, resulting in a bent Fe−
G
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O−Fe angle of ∼130° and a shorter Fe···Fe distance of ∼3.3
Å.27 In this paper, we demonstrate by EXAFS analysis that 1−F
has a Fe···Fe distance of 3.56 Å and consequently a nearly
linear Fe−O−Fe angle due to the absence of a hydrogen bond.
The presence of the H-bond in 1−OH may be responsible for
attenuating the H-atom abstracting capability of 1−OH.
However, the present DFT calculations comparing 1−OH
and 1−F strongly suggest that the H-bond in 1−OH does not
significantly change the electrophilicity of the reactive FeIVO
unit but instead increases the activation barrier for C−H bond
cleavage by requiring the weakening of the H-bond in the
course of HAT by the oxoiron(IV) moiety. This study thus
sheds light on how nature might employ hydrogen bonding to
modulate the reactivities of oxoiron(IV) intermediates in the
active sites of various dioxygen activating iron enzymes.
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ASSOCIATED CONTENT
■
(19) Nordlund, P.; Reichard, P. Annu. Rev. Biochem. 2006, 75, 681−
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S
* Supporting Information
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of charge via the Internet at http://pubs.acs.org.
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AUTHOR INFORMATION
■
Corresponding Author
*E-mail: shengfa.ye@cec.mpg.de (S.Y.), frank.neese@cec.mpg.
de (F.N.), larryque@umn.edu (L.Q.).
Kauffmann, K.; Munck, E. J. Am. Chem. Soc. 1995, 117, 2778−2792.
Notes
̈
(24) Xue, G.; Wang, D.; De Hont, R.; Fiedler, A. T.; Shan, X.;
The authors declare no competing financial interest.
Munck, E.; Que, L., Jr. Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 20713−
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20718.
ACKNOWLEDGMENTS
■
(25) Xue, G.; De Hont, R.; Munck, E.; Que, L., Jr. Nat. Chem. 2010,
̈
The work at Minnesota was supported by U.S. National
Institutes of Health via grant GM-38767 to L.Q. and
postdoctoral fellowship GM-079839 to A.T.F. C.-Y.G. grate-
fully acknowledges a grant from China Scholarship Council
(CSC). C.-Y.G., S.Y., and F.N. gratefully acknowledge financial
support by the German Science Foundation (DFG), the
University of Bonn, and the Max Planck Society. XAS data were
collected on beamline 7-3 at the Stanford Synchrotron
Radiation Laboratory (SSRL), a national user facility operated
by Stanford University on behalf of the U.S. Department of
Energy, Office of Basic Energy Sciences. The SSRL Structural
Molecular Biology Program is supported by the Department of
Energy, Office of Biological and Environmental Research, and
by the National Institutes of Health, National Center for
Research Resources, and Biomedical Technology Program.
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