Isolation and characterization of a dihydroxo-bridged iron(III,III)(μ- OH)2 diamond core derived from dioxygen

Article abstract of DOI:10.1021/ic4010906

Dioxygen addition to coordinatively unsaturated [Fe(II)(O ^Me2N₄(6-Me-DPEN))](PF₆) (1) is shown to afford a complex containing a dihydroxo-bridged Fe(III)₂(μ-OH) ₂ diamond core, [Fe^III(O^Me2N ₄(6-Me-DPEN))]₂(μ-OH)₂(PF₆) ₂·(CH₃CH₂CN)₂ (2). The diamond core of 2 resembles the oxidized methane monooxygenase (MMOox) resting state, as well as the active site product formed following H-atom abstraction from Tyr-OH by ribonucleotide reductase (RNR). The Fe-OH bond lengths of 2 are comparable with those of the MMOHox suggesting that MMOHox contains a Fe(III)₂(μ-OH)₂ as opposed to Fe(III) ₂(μ-OH)(μ-OH₂) diamond core as had been suggested. Isotopic labeling experiments with ¹⁸O₂ and CD ₃CN indicate that the oxygen and proton of the μ-OH bridges of 2 are derived from dioxygen and acetonitrile. Deuterium incorporation (from CD₃CN) suggests that an unobserved intermediate capable of abstracting a H-atom from CH₃CN forms en route to 2. Given the high C-H bond dissociation energy (BDE = 97 kcal/mol) of acetonitrile, this indicates that this intermediate is a potent oxidant, possibly a high-valent iron oxo. Consistent with this, iodosylbenzene (PhIO) also reacts with 1 in CD ₃CN to afford the deuterated Fe(III)₂(μ-OD)₂ derivative of 2. Intermediates are not spectroscopically observed in either reaction (O₂ and PhIO) even at low-temperatures (-80 C), indicating that this intermediate has a very short lifetime, likely due to its highly reactive nature. Hydroxo-bridged 2 was found to stoichiometrically abstract hydrogen atoms from 9,10-dihydroanthracene (C-H BDE = 76 kcal/mol) at ambient temperatures.

Full text of DOI:10.1021/ic4010906

Article
pubs.acs.org/IC
Isolation and Characterization of a Dihydroxo-Bridged
Iron(III,III)(μ-OH)2 Diamond Core Derived from Dioxygen
Michael K. Coggins, Santiago Toledo, and Julie A. Kovacs*
The Department of Chemistry, University of Washington: Box 351700 Seattle, Washington 98195-1700, United States
S
* Supporting Information
ABSTRACT: Dioxygen addition to coordinatively unsatu-
rated [Fe(II)(OMe2N4(6-Me-DPEN))](PF6) (1) is shown to
afford a complex containing a dihydroxo-bridged Fe(III)2(μ-OH)2
diamond core, [FeIII(OMe2N4(6-Me-DPEN))]2(μ-OH)2(PF6)2·
(CH3CH2CN)2 (2). The diamond core of 2 resembles the
oxidized methane monooxygenase (MMOox) resting state, as well
as the active site product formed following H-atom abstraction
from Tyr-OH by ribonucleotide reductase (RNR). The Fe-OH
bond lengths of 2 are comparable with those of the MMOHox
suggesting that MMOHox contains a Fe(III)2(μ-OH)2 as opposed
to Fe(III)2(μ-OH)(μ-OH2) diamond core as had been suggested.
Isotopic labeling experiments with 18O2 and CD3CN indicate that
the oxygen and proton of the μ-OH bridges of 2 are derived from
dioxygen and acetonitrile. Deuterium incorporation (from CD3CN) suggests that an unobserved intermediate capable of abstracting a
H-atom from CH3CN forms en route to 2. Given the high C−H bond dissociation energy (BDE = 97 kcal/mol) of acetonitrile, this
indicates that this intermediate is a potent oxidant, possibly a high-valent iron oxo. Consistent with this, iodosylbenzene (PhIO) also
reacts with 1 in CD3CN to afford the deuterated Fe(III)2(μ-OD)2 derivative of 2. Intermediates are not spectroscopically observed in
either reaction (O2 and PhIO) even at low-temperatures (−80 °C), indicating that this intermediate has a very short lifetime, likely due to
its highly reactive nature. Hydroxo-bridged 2 was found to stoichiometrically abstract hydrogen atoms from 9,10-dihydroanthracene
(C−H BDE = 76 kcal/mol) at ambient temperatures.
Scheme 1
INTRODUCTION
■
The activation of O2 is involved in many fundamental biochemical
processes promoted by iron metalloenzymes. These transformations
typically involve reactive iron-superoxo, -peroxo or high-valent oxo
intermediates,1−12 which are, in some cases, capable of activating
strong C−H bonds.1,13−15 For example, cytochrome P450
binds and subsequently activates O2 en route to an Fe(IV)-OH
porphyrin intermediate (Compound II).13,15 Nonheme iron
enzymes, such as α-ketoglutarate taurine dioxygenase (TauD)11,16
and halogenase SyrB2,17 activate O2 to form high-valent Fe(IV)-oxo
intermediates. The reduced binuclear Fe(II)2 active site of methane
monooxygenase (MMO)1,10,18−21 and ribonucleotide reductase
(RNR)10,22−25 react with O2 to afford highly reactive oxidized
binuclear Fe(IV)2(μ-O)2 (A) or M(III)(μ-O)(μ-OH)M′(IV)
(M, M′ = Mn, Fe; B) diamond cores,26−28 respectively (Scheme 1),
which abstract H-atoms from either CH4 or TyrOH, respectively,
to afford Fe(III)(μ-OH)(μ-O)Fe(IV) (B) or M(III)(μ-
OH)2M′(III) (C) species.3,19,21,25,29,30 The highly reactive nature
of these enzymatic intermediates has prompted numerous
investigations aimed at establishing benchmark structural,
spectroscopic, and reactivity properties of these spe-
cies.1,4,10−12,16,18−28,31−36 With RNR, the introduction of an
electron along with O2 affords structure B (Scheme 1), which in
Chlamydia tranchomatis has been shown to contain an oxo/
hydroxo bridged Fe(III)Mn(IV) dimer based on Mn and Fe
K-edge EXAFS and DFT calculations.25 It is likely that the di-
iron RNRs have an analogous Fe(III)Fe(IV) core B that converts
to core C upon reaction with Tyr-OH substrate (eq 1). The
significantly stronger C−H bond of CH4 requires the higher
Received: May 2, 2013
Published: November 14, 2013
© 2013 American Chemical Society
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(0.20 g, 0.74 mmol), 3-hydroxy-3-methyl-2-butanone (0.09 g, 0.86 mmol),
NaOCH3 (0.40 g, 0.74 mmol), and NaPF6 (0.12 g, 0.74 mmol) were
combined in CH3OH (10 mL) and allowed to stir under an inert
atmosphere in a glovebox at room temperature for two days. All
volatiles were then removed in vacuo to yield a crude yellow solid,
which was recrystallized from CH3CN/Et2O at 258 K to yield the title
compound as a bright yellow solid in 47% yield (0.20 g, 0.35 mmol).
Electronic absorption spectrum: λmax (nm) (ε (M−1 cm−1))
(CH3CN): 412 (250). Redox potential (CH3CN vs Fc+/0, 298 K):
Epa = +230 mV, Epc = +10 mV, ΔE = 220 mV. Magnetic moment
(299 K, CD3OD solution): 4.71 μB. ESI-MS: Expected m/z for
[C21H29N4OFe]+ = 409.3, found m/z = 409.2. Elemental analysis
valent core A (Scheme 1) of methane monooxygenase (MMO)
to abstract an H-atom. It has been debated as to whether the
structure of the MMO oxidized resting state (MMOHox)
contains a bis-hydroxo bridged Fe(III)(μ-OH)2Fe(III) (C) or
a hydroxo/aquo bridged Fe(III)(μ-OH)(μ-OH2)Fe(III) (D)
core.21,37−39 One would expect the metal ion Lewis acidity of
Fe(III) and Fe(IV) to disfavor protonation of a hydroxide
especially if it is bridging. Water has been observed to bridge
between two less Lewis acidic Fe(II) ions, however.40
Many of the insights regarding the reactivity structures and
properties of these oxidized bimetallic diamond cores have been
provided by synthetic analogues.4,12,31−36 With synthetic
complexes, solubility in nonaqueous solvents with low freezing
points and small molecule crystallography can help provide
mechanistic details, such as the probable identity and
spectroscopic properties of reaction intermediates18,41−45 or the
location of and transfer of key protons.46 Research efforts in our
group have recently focused on the O2 reactivity of biologically
relevant first-row transition metal complexes.47,48 Herein we
describe the reactivity of a new coordinatively unsaturated Fe(II)
complex with O2 to afford a dihydroxo-bridged binuclear Fe(III)
complex. Spectroscopic evidence is reported which suggests that
an unobserved intermediate formed during this reaction abstracts
a hydrogen atom from CH3CN solvent.
−
results were obtained with the BPh4 salt of 1, which was synthesized
by the same procedure described above except that NaBPh4 was used
instead of NaPF6. Elemental analysis for C45H49N4BOFe; Calculated
C, 72.06; H, 7.16; N, 6.86. Found C, 71.11; H, 7.60; N, 6.41.
Synthesis of [FeIII(OMe2N4(6-Me-DPEN))]2(μ-OH)2(PF6)2·
(CH3CH2CN)2 (2). Complex 1 (0.20 g, 0.36 mmol) was dissolved in
CH3CN (5 mL) under an inert atmosphere in a glovebox at room
temperature. The resulting solution was placed into a gastight syringe,
removed from the glovebox, and injected into a custom-made two-
neck vial equipped with a septum cap that had previously been purged
with argon and contained a stir bar. Dioxygen, from a pressurized tank
(Praxair, 99.9999%, <0.5 ppm H2O) and run through a column of
anhydrous CaSO4 (Drierite), was gently bubbled into the stirring
solution for approximately five minutes. The reaction mixture was
allowed to continue stirring at room temperature for two hours, during
which time the solution had turned from yellow to dark orange. All volatiles
were then removed in vacuo to yield a dark orange solid, which was
recrystallized from CH3CN/Et2O (1/6 vol/vol) at 253 K to afford the
title compound in 96% yield (0.19 g, 0.17 mmol). X-ray quality crystals
of 2 were grown from a concentrated CH3CH2CN solution at −80 °C,
as well as from a concentrated CH3CN solution at room temperature.
FT-IR (NaCl plates, Nujol mull, 298 K): ν(O−H) = 3610 cm−1;
ν(O−D) = 2730 cm−1. Elemental analysis for C42H58N8O4F12P2Fe2;
Calculated C, 44.50; H, 5.69; N, 10.61. Found C, 45.84; H, 5.33;
N, 10.40.
Characterization of 2 in CH3CN Solution. Electronic absorption
spectrum: λmax (nm) (ε (M−1 cm−1)): 310 (610), 375 (br, 440)
(extinction coefficients calculated per Fe(III)). Redox potential
(CH3CN vs Fc+/0, 298 K): Epa = +235 mV, Epc = +26 mV. Magnetic
moment (300 K, CD3CN solution): 5.82 μB/Fe(III). ESI-MS: Expected
m/z for [C21H30N4O2Fe]+ = 426.3, found m/z = 426.2. Expected m/z for
[C21H29DN4O2Fe]+ = 427.3, found m/z = 427.2. Expected m/z for
[C21H30N4O18OFe]+ = 428.3, found m/z = 428.2. EPR spectrum
(1:1 CH3CN/toluene glass, 14 K): g = 1.96, 4.07, 10.2.
Synthesis and Isolation of Deuterium Labeled
[FeIII(OMe2N4(6-Me-DPEN))]2(μ-OD)2(PF6)2·(CH3CH2CN)2 (2) for
FT-IR Experiments. Method 1. A solution of 1 (0.25 g, 0.45 mmol)
was prepared in dry CD3CN (30 mL; Cambridge Isotopes (99.8%))
under an inert atmosphere in a glovebox. The resulting solution was
placed into a gastight syringe, removed from the glovebox, and
injected into a custom-made two-neck vial equipped with a septum cap
that had previously been purged with argon and contained a stir bar.
Dioxygen, derived from a pressurized tank (Praxair, 99.9999%, <0.5
ppm H2O) and run through a column of anhydrous CaSO4 (Drierite),
was gently bubbled into the stirring solution for approximately five
minutes. The reaction was allowed to continue to stir at room
temperature for 30 min, after which all volatiles were removed in vacuo
to afford 2 as a dark orange solid. The resulting solid was redissolved in a
minimal amount of CH3CH2CN and crystallized at −80 °C. Crystalline
samples of 2 were harvested from the mixture via filtration through a fine
fritted filter, briefly dried in vacuo at room temperature, and subsequently
used for FT-IR experiments.
EXPERIMENTAL SECTION
■
General Methods. All manipulations were performed using
Schlenk line techniques or under a N2 atmosphere in a glovebox.
The highest purity reagents and solvents available were purchased and
used without further purification unless otherwise noted. CH3OH and
CH3CN (CaH2) were dried and distilled prior to use. Et2O was
purified using solvent purification columns housed in a custom
stainless steel cabinet and dispensed by a stainless steel Schlenk-line
(GlassContour). CD3CN and CD2Cl2 were purchased from Cambridge
Isotope Laboratories, Inc. CD3CN was either dried over CaH2, vacuum
transferred and stored in a drybox, or obtained from sealed ampules
(Cambridge Isotopes (99.8%)) containing volumes small enough for a
1
single experiment. All solvents were rigorously degassed prior to use. H
NMR spectra were recorded on either a Bruker AV 301 or Bruker AV 300
FT NMR spectrometer at ambient temperature and were referenced to
residual deuterated solvent. Infrared spectra were recorded on NaCl salt
plates as Nujol mulls with a Perkin-Elmer 1720 FT-IR spectrometer.
Electrospray-ionization mass spectra were obtained on a Bruker Esquire
Liquid Chromatograph−Ion Trap mass spectrometer. Gas chromatography−
mass spectrometry data were recorded using an HP 5971A gas
chromatograph interfaced with a quadrupole mass spectrometer equipped
with a 7673A autosampler. Electronic absorption spectra were recorded
on a Varian Cary 50 spectrophotometer equipped with a fiber optic cable
connected to a “dip” ATR probe (C-technologies). A custom-built two-
neck solution sample holder equipped with a threaded glass connector
was sized specifically to fit the “dip” probe. Cyclic voltammograms were
recorded in CH3CN (100 mM (nBu4N)(PF6) supporting electrolyte)
on a PAR 263A potentiostat with a glassy carbon working electrode,
Ag/AgNO3 reference electrode, and a platinum auxiliary electrode. EPR
spectra were recorded on a Varian CW-EPR spectrometer at 15 K
equipped with an Oxford helium cryostat. Solution magnetic moments
were calculated by the Evans method,49 with temperature corrections
made in the manner described by Van Geet.50 Pascal’s constants were
used to correct for diamagnetic contributions to the experimental
magnetic moment. X-ray crystallography data was recorded on a Bruker
APEX II single crystal X-ray diffractometer with Mo-radiation. Elemental
analyses were performed by Atlantic Microlabs, Norcross, GA. Experi-
ments involving iodosylbenzene were conducted using a 2 mM stock
solution in CH3OH. N,N-bis(6-methyl-2-pyridilmethyl)ethane-1,2-dia-
mine (6-Me-DPEN) was prepared according to literature procedures.48
Synthesis of [FeII(OMe2N4(6-Me-DPEN))](PF6) (1). FeCl2 (0.094
g, 0.74 mmol), N,N-bis(6-methyl-2-pyridilmethyl)ethane-1,2-diamine
Method 2. A solution of 2 (0.090 g, 0.16 mmol) was prepared in
dry CH3CN (10 mL) under aerobic conditions at room temperature.
D2O (0.1 mL) was added to this solution, and the resulting reaction
mixture was allowed to gently stir at room temperature overnight. All
volatiles were then removed in vacuo to afford a dark orange solid,
which was left under vacuum for 72 h. The solid was then redissolved
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Table 1. Crystal Data for [FeII(OMe2N4(6-Me-DPEN))](PF6)
(1) and [FeIII(OMe2N4(6-Me-DPEN))]2(μ-OH)2(PF6)2·
(CH3CH2CN)2 (2)
in a minimal amount of CH3CH2CN, crystallized at −80 °C, harvested
via filtration, and subsequently used for FT-IR experiments.
Analysis of Products From Reactions Between Complex 2
and 9,10-Dihydroanthracene in CH3CN. In a typical reaction, 2
was dissolved in CH3CN (3−4 mL, ∼0.5 mM solution of 2) at room
temperature under an inert atmosphere in a glovebox. The resulting
solution was placed into a gastight syringe, removed from the
glovebox, and injected into a custom-made two-neck vial containing a
stir bar and equipped with a septum cap and threaded dip-probe feed-
through adaptor that had previously been purged with Ar. 9,10-
Dihydroanthracene (0.5 equivalents per Fe(III)) was then added to
the solution in a similar fashion from a concentrated stock solution
that had been prepared in CH3CN in a glovebox. Each reaction
mixture (the reaction was repeated three times and shown to be
reproducible in all three cases) was allowed to stir under anaerobic
conditions for 10−15 min, and then dried in vacuo. The solid products
were then washed with Et2O (3 mL) and the Et2O soluble
components were subsequently analyzed by GC/MS and quantified
using standard calibration curves.
X-ray Crystallography. A yellow crystal of 1 with dimensions
0.05 × 0.04 × 0.4 mm3 was mounted on a glass capillary with oil. Data
was collected at −143 °C. The crystal-to-detector distance was set to
30 mm and exposure time was 60 s per degree for all sets of exposure.
The scan width was 2.0°. Data collection was 99.4% complete to 25.0°
in ϑ. A total of 56,116 partial and complete reflections were collected
covering the indices, h = −21 to 21, k = −19 to 19, l = −32 to 32.
69,506 reflections were symmetry independent and the Rint = 0.125
indicated that the data was poor. Indexing and unit cell refinement
indicated an orthorhombic P lattice with the space group Pbca (No. 61).
A pale red plate of 2 with dimensions 0.20 × 0.10 × 0.10 mm3 was
mounted on a glass capillary with oil. Data was collected at −173 °C.
The crystal-to-detector distance was set to 40 mm and exposure time
was 30 s per degree for all sets of exposure. The scan width was 0.5°.
Data collection was 99.9% complete to 25.0° in ϑ. A total of 51,770
partial and complete reflections were collected covering the indices,
h = −15 to 14, k = −15 to 15, l = −17 to 17. 7,264 reflections were
symmetry independent and the Rint = 0.0512 indicated that the data
was good. Indexing and unit cell refinement indicated a triclinic P
lattice with the space group P−1 (No. 2).
1
2
Formula
MW
C21H29F6FeN4OP
553.40
C48H70F12Fe2N10O4P2
1252.78
100(2)
T, K
130(2)
Orthorhombic
15.9090(11)
17.1316(12)
17.6610(13)
90
Unit Cell
a, Å
Triclinic
11.237(2)
11.403(2)
13.334(2)
70.554(9)
66.281(9)
87.391(10)
1467.3(5)
1
b, Å
c, Å
α, deg
β, deg
γ, deg
V, Å3
90
90
4813.3(6)
8
Z
d (calc), g/cm3
Space group
R
1.530
1.418
Pbca
P−1
0.0366
0.0592
Rw
0.1548
0.0796
GOF
0.928
1.007
Table 2. Selected Bond Distances (Å) and Bond Angles
(deg) for [FeII(OMe2N4(6-Me-DPEN))](PF6) (1) and
[FeIII(OMe2N4(6-Me-DPEN))]2(μ-OH)2(PF6)2·
(CH3CH2CN)2 (2)
1
2
Fe(1)−O(1)
Fe(1)−N(1)
Fe(1)−N(2)
Fe(1)−N(3)
Fe(1)−N(4)
Fe(1)−O(2)
Fe(1′)−O(2)
Fe(1)···Fe(1′)
1.925(3)
2.086(4)
2.273(5)
2.139(4)
2.121(4)
N/A
1.8721(13)
2.1121(15)
2.2556(15)
2.2144(16)
N/A
1.9715(13)
2.0037(14)
3.172
N/A
All data was integrated and scaled using SAINT, SADABS within
the APEX2 software package by Bruker. Solutions by direct methods
(SHELXS, SIR97) produced complete heavy atom phasing models
which were consistent with each proposed structure. Scattering factors
are from Waasmair and Kirfel.51 Crystal data for 1 and 2 are provided
in Table 1. All non-hydrogen atoms were refined anistropically by full-
matrix least-squares methods. Most hydrogen atoms were placed using
a riding model; however, the hydrogen atoms on the bridging
hydroxide ligands in 2 were refined from the difference map.
Crystallographic data is summarized in Table 1. Selected distances
and angles are summarized in Table 2.
a
N/A
O(1)−Fe−N(1)
O(1)−Fe−N(2)
O(1)−Fe−N(3)
O(1)−Fe−N(4)
N(1)−Fe−N(3)
N(1)−Fe−N(4)
N(3)−Fe−N(4)
O(1)−Fe−O(2)
O(1)−Fe−O(2′)
N(1)−Fe−O(2)
Fe(1)−O(2)−Fe(1′)
O(2)−Fe(1)−O(2#)
78.97(16)
154.82(15)
117.97(16)
116.24(16)
116.03(17)
122.64(17)
104.41(15)
N/A
78.34(6)
148.61(5)
98.17(6)
N/A
107.26(6)
N/A
N/A
106.24(5)
104.88(6)
163.94(6)
105.88(6)
74.12(6)
N/A
N/A
RESULTS AND DISCUSSION
■
N/A
Synthesis and Structure of Coordinatively Unsatu-
rated Fe(II) Alkoxide Complex. The alkoxide-ligated
complex [FeII(OMe2N4(6-Me-DPEN))](PF6) (1) was synthe-
sized via an Fe(II)-templated Schiff-base condensation between
6-Me-DPEN48 and 3-hydroxy-3-methyl-2-butanone in CH3OH
under an inert atmosphere at ambient temperature. X-ray
quality crystals of 1 were obtained via vapor diffusion of Et2O
into a saturated CH3CN solution at room temperature. As
shown in the ORTEP diagram of Figure 1, the Fe(II) ion of 1 is
found in a distorted trigonal bipyramidal coordination environ-
ment (τ = 0.61)52 comprising an alkoxide oxygen (O(1)), imine
nitrogen (N(1)), tertiary amine (N(2)), and two pyridine
nitrogens (N(3) and N(4)) (Figure 1). Coordinatively unsatu-
rated 1 is high-spin (S = 2, μeff = 4.71 μB in CD3OD) and exhibits
a quasi-reverisble FeIII/II redox couple in CH3CN (under nitrogen)
with E1/2 = +120 mV vs Fc+/0 (ΔE = 220 mV, Figure S-1).
N/A
a
Fe(1) and Fe(1′) and O(2) and O(2′) are equivalent in 2 and related
by a crystallographically imposed inversion center, i.e., only one-half of
the dimer is crystallographically independent.
The room temperature electronic absorption spectrum of 1 in
CH3CN contains a single absorption band with λmax =412 nm
(ε = 250 M−1 cm−1 Figure S-2).
Reactivity with Dioxygen to Afford Dihydroxo-Bridged
Iron(III,III)(μ−OH)2 Diamond Core. If excess amounts of dry O2,
derived from a pressurized tank (Praxair, 99.9999%, <0.5 ppm H2O)
and dried via a column of anhydrous CaSO4 (Drierite), are bubbled
into a CH3CN solution of 1 for ∼2−3 min at ambient temperature
the solution changes from yellow to dark orange, a broad band at
λmax = 310 nm (Figure S-3) grows in in the electronic absorption
spectrum, and the broad band at 412 nm (Figure S-2) disappears.
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The Fe(1)···Fe(1′) distance in 2 (3.172 Å) is, on the other
hand, longer than the reported Fe(III)2(μ-OH)2 core range
(3.07−3.12 Å), while the Fe(1)−O(2)−Fe(1′) bridging angle
105.88(6)° is at the larger end of the previously reported range
(92.3−105.8°).53−63 This likely results from steric congestion
around each of the two Fe(III) ions, as is further indicated by the
dissociation of a pyridine arm away from each metal ion in both
halves of the dimer (Figure S-4).
Isotopic Labeling Experiments. Isotopic labeling studies
conducted with 18O2 confirmed that the two bridging hydroxide
ligands in 2 are indeed derived from O2 (Scheme 2; Figure S-5−
Scheme 2
Figure 1. ORTEP diagram (50% probability) of [FeII(OMe2N4(6-Me-
DPEN))]+ (1) with hydrogen atoms and counterion omitted for
clarity.
Low temperature reactions were also performed at either −40 °C
in CH3CN or −80 °C in CH3CH2CN; however, no transient
intermediates were observed under these conditions. X-ray quality
crystals of the orange product obtained from this reaction,
[FeIII(OMe2N4(6-Me-DPEN))]2(μ-OH)2(PF6)2·(CH3CH2CN)2
(2), were obtained in high yield (96%) via vapor diffusion of Et2O
into a concentrated CH3CH2CN solution at −80 °C (Figure S-4).
As shown in the ORTEP diagram of Figure 2, both Fe(III) ions of
Figure S-7). As shown by the Fe-isotope distribution pattern in
the ESI mass spectra of Figure 3a, the μ-hydroxo bridge cleaves
in the mass spectrometer to afford a monomeric monocationic
Fe-hydroxo species with a parent ion m/z peak at 426.2 (Figure S-5),
which corresponds to half of the {[FeIII(OMe2N4(6-Me-
DPEN))]2(μ-OH)2}2+ dimer 2, [FeIII(OMe2N4(6-Me-DPEN))-
(OH)]+, and is 17 mass units greater than that (m/z = 409.2) of
1 (Figure S-6). This parent ion peak (at m/z = 426.2; Figure 3a)
shifts by two mass units (to m/z = 428.2; Figure 3c) upon the
incorporation of 18O from 18O-labeled dioxygen (Figure S-7). In
order to determine the source of the hydrogen atoms found on
the hydroxide bridging ligands in 2, deuterium labeling studies
were conducted. If O2 is added to 1 in deuterated acetonitrile
(CD3CN), then a parent ion peak at m/z = 427.2 (Figure 3b),
which is shifted by one mass unit (Figure S-8) relative to that
observed at m/z = 426.2 (Figure 3a) in the CH3CN reaction
(Figure S-5), is observed consistent with the incorporation of
deuterium. Again, the Fe-isotope distribution pattern indicates
that the bis-hydroxo bridged di-iron complex cleaves in the mass
spectrometer to afford a monomeric [FeIII(OMe2N4(6-Me-
DPEN))(OD)]+. Although one cannot rule out some sort of
impurity in the CD3CN as the source of deuterium, it is unlikely
that D2O from “wet” CD3CN is responsible, given that the 18O-
label in the spectrum of Figure 3c is not “washed out” via
exchange with water (H216O) contamination in the CH3CN. It is
also unlikely that D2O, as opposed to H2O, would be a
contaminant in the CD3CN. Deuterium labeled 2 was also
obtained from a reaction between 1 and O2 in CD2Cl2.
Additional evidence to support the incorporation of deuterium from
CD3CN is shown by the vibrational spectrum (Figure S-9) of
crystalline 2 (synthesized in CH3CN), which displays a sharp
feature at 3610 cm−1 that shifts to 2730 cm−1 when 2 is synthesized
Figure 2. ORTEP diagram (50% probability) of the Fe(III)(μ-
OH)2Fe′(III) diamond core and Fe coordination sphere of dicationic-
{[FeIII(OMe2N4(6-Me-DPEN))]2(μ-OH)22+ (2). The two halves of the
molecule are related by a crystallographic inversion center. An ORTEP
diagram of the entire dicationic complex is shown in Figure S-4.
2 are located in a distorted octahedral environment consisting of
an alkoxide oxygen (O(1)), two hydroxide bridging ligands
(O(2) and O(2′)), an imine nitrogen (N(1)), a tertiary amine
(N(2)), and a pyridine nitrogen (N(3)) (Figure 2). The location
and refinement of a hydrogen atom on each of the bridging
oxygen atoms (O(2)) in the X-ray structure, along with the
−
presence of two PF6 counterions per diiron complex,
conclusively identified the bridging ligands of 2 as hydroxides.
Hydrogen-bonding interactions ((O(2)-H···N(21)) = 2.200 Å;
O(2)−H−N(21)= 171.29°) between the bridging hydroxide
ligands and co-crystallized CH3CH2CN nitrogens (Figure S-4)
further verified this assignment.
in CD3CN. The energies and observed isotopic shift (νO−H/νO−D
=
The hydroxide ligands in 2 are asymmetrically bridging with
Fe(1)−O(2) and Fe(1)-O(2′) bond lengths of 1.9715(13) Å
and 2.0037(14) Å, respectively (Table 2). These distances are
comparable to other structurally characterized Fe(III)2(μ-OH)2 and
Fe(III)2(μ-OH)2(μ-O2CR) complexes (1.88−2.08 Å).35,36,53−64
1.32 vs theoretical = 1.35) for these vibrational features are
consistent with O−H and O−D stretches, respectively.
Implications Regarding the Involvement of a Reactive
Intermediate. Deuterium incorporation (from CD3CN)
suggests that an unobserved intermediate capable of abstracting
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Article
Scheme 3
oxidized to anthracene in 23(3)% yield (Figures S-12, S-13).
Complex 2 was unreactive, however, with organic compounds
containing stronger C−H bonds, such as toluene and cyclo-
hexane (C−H BDFE = 87 kcal·mol−1 and 99 kcal·mol−1,
respectively).78 This reactivity is similar to other Fe(III)-OH
species, such as lipoxygenase79,80 and [FeIII(PY5)(OH)]2+,76
which have been found to abstract hydrogen atoms from
substrates containing relatively weak C−H bonds.
CONCLUSIONS
■
In conclusion, we have described the synthesis and character-
ization of a new coordinatively unsaturated Fe(II) complex (1)
that reacts with O2 to form an Fe(III)2(μ-OH)2 diamond core
(2) in high yield. Isotopic labeling studies suggest that an
unobserved intermediate formed during the conversion of 1 to
2 is capable of oxidizing CH3CN, presumeably via H• atom
transfer. Iodosylbenzene (PhIO, 1.0 equiv) also oxidizes 1 to
afford 2 in high yield in CH3CN. Although low temperature
intermediates were not observed during reactions between 1 and
either O2 or PhIO, an unobserved high-valent Fe(IV)O
intermediate, that is capable of, and responsible for, the observed
solvent oxidation, is proposed in both of these reactions. Reactivity
studies also showed that hydroxo-bridged 2 is itself also capable of
oxidizing the relatively weak C−H bonds of DHA at room
temperature. Efforts toward further exploration of this reactivity, as
well as comparing the properties and reactivity of thiolate-ligated
analogues, are currently underway.
Figure 3. ESI-MS of the cleaved monomeric product observed when
2+
dicationic {[FeIII(OMe2N4(6-Me-DPEN))]2(μ-OH)2 (2), obtained
from (a) the reaction between 1 and 16O2 in CH3CN, (b) the reaction
between 1 and 16O2 in CD3CN, and (c) the reaction between 1 and
18O2 in CH3CN, is placed in the mass spectrometer.
an H-atom from CH3CN forms in the dioxygen reaction
(Scheme 2) en route to 2. Given the high C−H bond
dissociation energy (BDE = 97 kcal/mol) of acetonitrile, this
indicates that this intermediate is a potent oxidant, possibly a
high-valent iron oxo. Consistent with this, iodosylbenzene
(PhIO) also reacts with 1 in CD3CN (Scheme 3) to afford the
deuterated Fe(III)2(μ-OD)2 derivative of 2 (93−96% yield), as
verified by FT-IR (νO−D= 2727 cm−1; Figure S-11) and ESI-MS
(m/z = 427.2; Figure S-10). Intermediates are not spectroscopi-
cally observed in either reaction (O2 and PhIO) even at low
temperatures (−80 °C), indicating that this intermediate has a
very short lifetime, likely due to its highly reactive nature.
Iodosylbenzene (PhIO) would be expected to afford a
Fe(IV)O upon its reaction with Fe(II) (Scheme 3).65−69
High-valent Fe(IV)O species have been shown to be highly
reactive and capable of abstracting H-atoms, especially in the
presence of anionic ligands.68−73 Hydrogen atom abstraction
from acetonitrile has been previously observed during the O2-
ASSOCIATED CONTENT
* Supporting Information
■
S
Cyclic voltammogram, electronic absorption spectrum, and
ESI-MS data for 1, and ESI-MS data for 2, and isotopic (18O
and D) derivatives thereof, derived from O2 and PhIO in
CH3CN or CD3CN. More detailed ORTEP diagram of 2, along
with crystallographic tables of both 1 and 2. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: kovacs@chem.washington.edu. Tel. (206)543-0713.
FAX (206)685-8665.
■
promoted oxidation of [Mn(II)1cyp 1− to [Mn(III)1cyp(OH)]1−
]
via a high-valent Mn-oxo intermediate.74 High-valent iron oxo
compounds [Fe(IV)(O)BnTPEN)]2+,75 [Fe(IV)(PY5)-
(O)]2+,76 and aqueous Fe(IV)O2+ have also been shown to
abstract hydrogen atoms from CH3CN.77
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
NIH funding (#RO1GM45881-20) is gratefully acknowledged.
Reactivity of Dihydroxo-Bridged 2 with Substrates Contain-
ing Weaker C−H Bonds. The reactivity of the dihydroxo-
bridged product 2 toward stoichiometric amounts of substrates
containing relatively weak C−H bonds was explored under anaerobic
conditions in CH3CN at room temperature. Under these conditions,
9,10-dihydroanthracene (C−H BDFE = 76.0 kcal·mol−1)78 was
■
REFERENCES
■
(1) Tinberg, C. E.; Lippard, S. J. Acc. Chem. Res. 2011, 44, 280−288.
(2) Kovaleva, E. G.; Lipscomb, J. D. Science 2007, 316, 453−456.
13329
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Inorganic Chemistry
Article
(3) Feig, A. L.; Lippard, S. J. Chem. Rev. 1994, 94, 759−805.
(4) Costas, M.; Mehn, M. P.; Jensen, M. P.; Que, L. J. Chem. Rev.
2004, 104, 939−986.
(39) Rosenzweig, A. C.; Nordlund, P.; Takahara, P. M.; Frederick, C.
A.; Lippard, S. J. Chem. Biol. 1995, 2, 409−418.
(40) Hagen, K. S.; Lachicotte, R. J. Am. Chem. Soc. 1992, 114, 8741−
8742.
(5) Cho, J.; Jeon, S.; Wilson, S. A.; Liu, L. V.; Kang, E. A.; Braymer, J.
J.; Lim, M. H.; Hedman, B.; Hodgson, K. O.; Valentine, J. S.; Solomon,
E. I.; Nam, W. Nat. Chem. 2011, 478, 502−505.
(41) Kodera, M.; Kawahara, Y.; Hitomi, Y.; Nomura, T.; Ogura, T.;
Kobayashi, Y. J. Am. Chem. Soc. 2012, 134, 13236−13239.
(42) Kim, K.; Lippard, S. L. J. Am. Chem. Soc. 1996, 118, 4914−4915.
(43) Dong, Y.; Menage, S.; Brennan, B. A.; Elgren, T. E.; Jang, H. G.;
Pearce, L. L.; Que, L. J. J. Am. Chem. Soc. 1993, 115, 1851−1859.
(44) Shook, R. L.; Gunderson, W. A.; Greaves, J.; Ziller, J. W.;
Hendrich, M. P.; Borovik, A. S. J. Am. Chem. Soc. 2008, 130, 8888−
8889.
(6) Krebs, C.; Fujimori, D. G.; Walsh, C. T.; Bollinger, J. M., Jr. Acc.
Chem. Res. 2007, 40, 484−492.
(7) Kovaleva, E. G.; Neibergall, M. B.; Chakrabarty, S.; Lipscomb, J.
D. Acc. Chem. Res. 2007, 40, 475−483.
(8) Que, L., Jr. Acc. Chem. Res. 2007, 40, 493−500.
(9) Kovacs, J. A. Science 2003, 299, 1024−1025.
(10) Solomon, E. I.; Brunold, T. C.; Davis, M. I.; Kemsley, J. N.; Lee,
S. K.; Lehnert, N.; Neese, F.; Skulan, A. J.; Yang, Y. S.; Zhou, J. Chem.
Rev. 2000, 100, 233−349.
(45) MacBeth, C. E.; Golombek, A. P.; Young, V. G., Jr.; Yang, C.;
Kuczera, K.; Hendrich, M. P.; Borovik, A. S. Science 2000, 289, 938−
941.
(11) Price, J. C.; Barr, E. W.; Tirupati, B.; Bollinger, J. M., Jr.; Krebs,
C. Biochemistry 2003, 42, 7497−7508.
(12) Que, L.; Tolman, W. B. Nature 2008, 455, 333−340.
(13) Rittle, J.; Green, M. T. Science 2010, 330, 933−937.
(14) Borovik, A. S. Chem. Soc. Rev. 2011, 40, 1870−1874.
(15) Sono, M.; Roach, M. P.; Coulter, E. D.; Dawson, J. H. Chem.
Rev. 1996, 96, 2841−2887.
(46) Shearer, J.; Scarrow, R. C.; Kovacs, J. A. J. Am. Chem. Soc. 2002,
124, 11709−11717.
(47) Theisen, R. M.; Shearer, J.; Kaminsky, W.; Kovacs, J. A. Inorg.
Chem. 2004, 43, 7682−7690.
(48) Coggins, M. K.; Sun, X.; Kwak, Y.; Solomon, E. I.; Rybak-
Akimova, E. V.; Kovacs, J. A. J. Am. Chem. Soc. 2013, 135, 5631−5640.
(49) Evans, D. A. J. Chem. Soc. 1959, 2005.
(16) Elkins, J. M.; Ryle, M. J.; Clifton, I. J.; Hotopp, J. C. D.; Lloyd, J.
S.; Burzlaff, N. I.; Baldwin, J. E.; Hausinger, R. P.; Roach, P. L.
Biochemistry 2002, 41, 5185−5192.
(50) Van Geet, A. L. Anal. Chem. 1968, 40, 2227−2229.
(51) Waasmaier, D.; Kirfel, A. Acta Crystallogr., Sect. A 1995, 51, 416.
(52) Addison, A. W.; Rao, T. N.; Reedijk, J. J. Chem. Soc., Dalton
Trans. 1984, 1349−1356.
(17) Matthews, M. L.; Krest, C. M.; Barr, E. W.; Vaillancourt, F. H.;
Walsh, C. T.; Green, M. T.; Krebs, C.; Bollinger, J. M., Jr. Biochemistry
2009, 48, 4331−4343.
(53) Matsumoto, K.; Egami, H.; Oguma, T.; Katsuki, T. Chem.
Commun. 2012, 48, 5823−5825.
(18) Xue, G.; Fiedler, A. T.; Martinho, M.; Munck, E.; Que, L., Jr.
Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 20615−20620.
(19) Valentine, A. M.; Stahl, S. S.; Lippard, S. J. J. Am. Chem. Soc.
1999, 121, 3876−3887.
́
(54) Bruijnincx, P. C. A.; Buurmans, I. L. C.; Huang, Y.; Juhasz, G.;
Viciano-Chumillas, M.; Quesada, M.; Reedijk, J.; Lutz, M.; Spek, A. L.;
Munck, E.; Bominaar, E. L.; Gebbink, R. J. M. K. Inorg. Chem. 2011,
̈
50, 9243−9255.
(20) Liu, K. E.; Valentine, A. M.; Wang, D.; Huynh, B. H.;
Edmondson, D. E.; Salifoglou, A.; Lippard, S. J. J. Am. Chem. Soc. 1995,
117, 10174−10185.
(55) Safaei, E.; Sheykhi, H.; Weyhermuller, T.; Bill, E. Inorg. Chim.
̈
Acta 2011, 384, 69−75.
(56) Egami, H.; Matsumoto, K.; Oguma, T.; Kunisu, T.; Katsuki, T. J.
Am. Chem. Soc. 2010, 132, 13633−13635.
(21) Merkx, M.; Kopp, D. A.; Sazinsky, M. H.; Blazyk, J. L.; Muller,
̈
(57) Boudalis, A. K.; Clemente-Juan, J. M.; Dahan, F.; Psycharis, V.;
Raptopoulou, C. P.; Donnadieu, B.; Sanakis, Y.; Tuchagues, J.-P. Inorg.
Chem. 2008, 47, 11314−11323.
J.; Lippard, S. J. Angew. Chem., Int. Ed. 2001, 40, 2782−2807.
(22) Bollinger, J. M., Jr.; Tong, W. H.; Ravi, N.; Huyuh, B. H.;
Edmondson, E. D.; Stubbe, J. J. Am. Chem. Soc. 1994, 116, 8015−8023.
(23) Bollinger, J. M., Jr.; Edmondson, D. E.; Huynh, B. H.; Filley, J.;
Norton, J. R.; Stubbe, J. Science 1991, 253, 292−298.
(24) Cotruvo, J. A., Jr.; Stich, T. A.; Britt, R. S.; Stubbe, J. J. Am.
Chem. Soc. 2013, 135, 4027−4039.
(58) Ghiladi, M.; Larsen, F. B.; McKenzie, C. J.; Sotofte, I.;
Tuchagues, J.-P. J. Chem. Soc., Dalton Trans. 2005, 1687−1692.
(59) Zheng, H.; Zang, Y.; Dong, Y.; Young, V. G.; Que, L. J. J. Am.
Chem. Soc. 1999, 121, 2226−2235.
(25) Younker, J. M.; Krest, C. M.; Jiang, W.; Krebs, C.; Bollinger, J.
M., Jr; Green, M. T. J. Am. Chem. Soc. 2008, 130, 15022−15027.
(26) Xue, G.; Geng, C.; Ye, S.; Fiedler, A. T.; Neese, F.; Que, L., Jr.
Inorg. Chem. 2013, 52, 3976−3984.
(60) Nanda, K. K.; Dutta, S. K.; Baitalik, S.; Venkatsubramanian, K.;
Nag, K. J. Chem. Soc., Dalton Trans. 1995, 1239−1244.
(61) Turowski, P. N.; Armstrong, W. H.; Liu, S.; Brown, S. N.;
Lippard, S. J. Inorg. Chem. 1994, 33, 636−645.
(62) Ou, C.-C.; Lalancette, R. A.; Potenza, J. A.; Schugar, H. J. J. Am.
Chem. Soc. 1978, 100, 2053−2057.
(27) Lee, S.-K.; Nesheim, J. C.; Lipscomb, J. D. J. Biol. Chem. 1993,
268, 21569−21577.
(63) Thich, J. A.; Ou, C. C.; Powers, D.; Vasiliou, B.; Mastropaolo,
D.; Potenza, J. A.; Schugar, H. J. J. Am. Chem. Soc. 1976, 98, 1425−
1433.
(64) Lee, D.; Pierce, B.; Krebs, C.; Hendrich, M. P.; Huynh, B. H.;
Lippard, S. J. J. Am. Chem. Soc. 2002, 124, 3993−4007.
(65) Rohde, J.-U.; In, J. H.; Lim, M. H.; Brennessel, W. W.;
Bukowski, M. R.; Stubna, A.; Munck, E.; Nam, W.; Que, L., Jr. Science
2003, 299, 1037−1039.
(66) Groves, J. T.; Haushalter, R. C.; Nakamura, M.; Nemo, T. E.;
Evans, B. J. J. Am. Chem. Soc. 1981, 103, 2884−2886.
(67) Ye, W.; Ho, D. M.; Friedle, S.; Palluccio, T. D.; Rybak-Akimova,
E. V. Inorg. Chem. 2012, 51, 5006−5021.
(68) Nam, W.; Jin, S. W.; Lim, M. H.; Ryu, J. Y. Inorg. Chem. 2002,
41, 3647−3652.
(69) Sastri, C. V.; Park, M. J.; Ohta, T.; Jackson, T. A.; Stubna, A.;
Seo, M. S.; Lee, J.; Kim, J.; Kitagawa, T.; Munck, E.; Que, L., Jr.; Nam,
W. J. Am. Chem. Soc. 2005, 127, 12494−12495.
(70) Nam, W. Acc. Chem. Res. 2007, 40, 522−531.
(71) Rhode, J.-U.; Que, L., Jr. Angew. Chem., Int. Ed. 2005, 44, 2255−
2258.
(28) Que, L. J.; Tolman, W. B. Angew. Chem., Int. Ed. 2002, 41,
1114−1137.
(29) Brunold, T. C. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 20641−
20642.
(30) Tshuva, E. Y.; Lippard, S. J. Chem. Rev. 2004, 104, 987−1012.
(31) Decker, A.; Solomon, E. I. Angew. Chem., Int. Ed. 2005, 44,
2252−2255.
(32) Xue, G.; Wang, D.; De Hont, R.; Fiedler, A. T.; Shan, X.;
Munck, E.; Que, L., Jr. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 20173−
20178.
(33) Borovik, A. S. Acc. Chem. Res. 2005, 38, 54−61.
(34) Shook, R. L.; Peterson, S. M.; Greaves, J.; Moore, C.; Rheingold,
A. L.; Borovik, A. S. J. Am. Chem. Soc. 2011, 133, 5810−5817.
(35) Lee, D.; Lippard, S. J. J. Am. Chem. Soc. 1998, 120, 12153−
12154.
(36) Lee, D.; Lippard, S. J. J. Am. Chem. Soc. 2001, 123, 4611−4612.
(37) Tinberg, C. E.; Lippard, S. J. Biochemistry 2010, 49, 7902−7912.
(38) Elango, N.; Radhakrishnan, R.; Forland, W. A.; Wallar, B. J.;
Earhart, C. A.; Lipscomb, J. D.; Ohlendorf, D. H. Protein Sci. 1997, 6,
556−568.
13330
dx.doi.org/10.1021/ic4010906 | Inorg. Chem. 2013, 52, 13325−13331

Inorganic Chemistry
Article
(72) Hirao, H.; Kumar, D.; Que, L., Jr.; Shaik, S. J. Am. Chem. Soc.
2006, 128, 8590−8606.
(73) Schlichting, I.; Berendzen, J.; Chu, K.; Stock, A. M.; Maves, S.
A.; Benson, D. E.; Sweet, R. M.; Ringe, D.; Petsko, G. A.; Sligar, S. G.
Science 2000, 287, 1615−1622.
(74) Shirin, Z.; Young, V. G., Jr.; Borovik, A. S. Chem. Commun.
1997, 1967−1968.
(75) Klinker, E. J.; Shaik, S.; Hirao, H.; Que, L., Jr. Angew. Chem., Int.
Ed. 2009, 48, 1291−1295.
(76) Goldsmith, C. R.; Stack, T. D. P. Inorg. Chem. 2006, 45, 6048−
6055.
(77) Pestovsky, O.; Bakac, A. J. Am. Chem. Soc. 2004, 126, 13757−
13764.
(78) Warren, J. J.; Tronic, T. A.; Mayer, J. M. Chem. Rev. 2010, 110,
6961−7001.
(79) Neidig, M. L.; Wecksler, A. T.; Schenk, G.; Holman, T. R.;
Solomon, E. I. J. Am. Chem. Soc. 2007, 129, 7531−7537.
(80) Lehnert, N.; Solomon, E. I. J. Biol. Inorg. Chem. 2003, 8, 294−
305.
13331
dx.doi.org/10.1021/ic4010906 | Inorg. Chem. 2013, 52, 13325−13331