O2 Activation by Non-Heme Thiolate-Based Dinuclear Fe Complexes

Article abstract of DOI:10.1021/acs.inorgchem.9b03633

Iron centers featuring thiolates in their metal coordination sphere (as ligands or substrates) are well-known to activate dioxygen. Both heme and non-heme centers that contain iron-thiolate bonds are found in nature. Investigating the ability of iron-thiolate model complexes to activate O₂ is expected to improve the understanding of the key factors that direct reactivity to either iron or sulfur. We report here the structural and redox properties of a thiolate-based dinuclear Fe complex, [Fe^II₂(LS)₂] (LS^2- = 2,2′-(2,2′-bipyridine-6,6′-iyl)bis(1,1-diphenylethanethiolate)), and its reactivity with dioxygen, in comparison with its previously reported protonated counterpart, [Fe^II₂(LS)(LSH)]⁺. When reaction with O₂ occurs in the absence of protons or in the presence of 1 equiv of proton (i.e., from [Fe^II₂(LS)(LSH)]⁺), unsupported μ-oxo or μ-hydroxo Fe^III dinuclear complexes ([Fe^III₂(LS)₂O] and [Fe^III₂(LS)₂(OH)]⁺, respectively) are generated. [Fe^III₂(LS)₂O], reported previously but isolated here for the first time from O₂ activation, is characterized by single crystal X-ray diffraction and M?ssbauer, resonance Raman, and NMR spectroscopies. The addition of protons leads to the release of water and the generation of a mixture of two Fe-based oxygen-free species. Density functional theory calculations provide insight into the formation of the μ-oxo or μ-hydroxo Fe^III dimers, suggesting that a dinuclear μ-peroxo Fe^III intermediate is key to reactivity, and the structure of which changes as a function of protonation state. Compared to previously reported Mn-thiolate analogues, the evolution of the peroxo intermediates to the final products is different and involves a comproportionation vs a dismutation process for the Mn and Fe derivate, respectively.

Full text of DOI:10.1021/acs.inorgchem.9b03633

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O2 Activation by Non-Heme Thiolate-Based Dinuclear Fe Complexes
́
́
Lianke Wang, Marcello Gennari,* Fabian G. Cantu Reinhard, Sandeep K. Padamati, Christian Philouze,
David Flot, Serhiy Demeshko, Wesley R. Browne, Franc Meyer, Sam P. de Visser,* and Carole Duboc*
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ABSTRACT: Iron centers featuring thiolates in their metal
coordination sphere (as ligands or substrates) are well-known to
activate dioxygen. Both heme and non-heme centers that contain
iron-thiolate bonds are found in nature. Investigating the ability of
iron−thiolate model complexes to activate O2 is expected to
improve the understanding of the key factors that direct reactivity
to either iron or sulfur. We report here the structural and redox
properties of a thiolate-based dinuclear Fe complex, [FeII (LS)2]
2
(LS2− = 2,2′-(2,2′-bipyridine-6,6′-iyl)bis(1,1-diphenylethanethiolate)), and its reactivity with dioxygen, in comparison with its
previously reported protonated counterpart, [FeII (LS)(LSH)]+. When reaction with O2 occurs in the absence of protons or in the
2
presence of 1 equiv of proton (i.e., from [FeII (LS)(LSH)]+), unsupported μ-oxo or μ-hydroxo FeIII dinuclear complexes
2
([FeIII2(LS)2O] and [FeIII2(LS)2(OH)]+, respectively) are generated. [FeIII2(LS)2O], reported previously but isolated here for the
̈
first time from O2 activation, is characterized by single crystal X-ray diffraction and Mossbauer, resonance Raman, and NMR
spectroscopies. The addition of protons leads to the release of water and the generation of a mixture of two Fe-based “oxygen-free”
species. Density functional theory calculations provide insight into the formation of the μ-oxo or μ-hydroxo FeIII dimers, suggesting
that a dinuclear μ-peroxo FeIII intermediate is key to reactivity, and the structure of which changes as a function of protonation state.
Compared to previously reported Mn−thiolate analogues, the evolution of the peroxo intermediates to the final products is different
and involves a comproportionation vs a dismutation process for the Mn and Fe derivate, respectively.
In this context, chemists have developed a broad range of
synthetic non-heme iron−thiolate model complexes. They can
be divided into three main classes based on their reactivity with
dioxygen: (i) those leading to the production of S-oxygenated
species, such as sulfenic, sulfinic, and sulfonic acid deriva-
tives;17−24 (ii) those promoting sulfur oxidation to generate
disulfide;25−27 and (iii) those forming iron−oxygen adducts, in
which the thiolate ligand remains unmodified. The last case
includes mono- or dinuclear FeII-thiolate precursors that
invariably generate unsupported μ-oxo bridged FeIII dimers
in the presence of O2.28−30
Efforts continue to expand the library of O2-reactive Fe−
thiolate complexes in view of preferentially directing the
reactivity to iron or sulfur, and in the last case to control the
selectivity, i.e., sulfoxygenation vs disulfide formation. Such an
objective requires the complete understanding of the various
reaction mechanisms and the identification of the key factors,
in terms of ligand design, metal spin state, and position of the
metal-bound thiolate with respect to the O2 activation site.
INTRODUCTION
■
Iron centers play a key role in dioxygen binding and activation,
in both enzymes and synthetic complexes.1−5 Apart from the
most classical N- and O-based donor ligands, a subclass of iron
centers that activate O2 features thiolates in the metal
coordination sphere, whether as supporting ligands or as
substrates. In nature, Fe−S(cysteinate) bonds are found in the
heme centers present in cytochromes P450,6,7 which enable
monoxygenation of inert C−H bonds. The structurally
analogous nitric oxide synthase8 releases the cellular signaling
molecule nitric oxide (NO) through a reaction of dioxygen
with L-arginine on a heme center. Regarding biological non-
heme Fe centers, several enzymes are able to carry out
reactions between O2 and thiolate-based substrates through
Fe−S bond formation. These include thiol oxygenases, among
which are the cysteine dioxygenase9−15 responsible for the
oxidation of cysteine to cysteine sulfinic acid, and the
isopenicillin N synthase,16 which enables the oxidation of the
thiolate-containing tripeptide δ-(L-α-aminoadipoyl)-L-cystein-
yl-D-valine to form isopenicillin N. In addition to the reactivity
of these two families of Fe-based metalloenzymes, the
coordination mode of the thiolate to the metal center is also
different: in non-heme systems, the thiolate binds in the cis
position with respect to the O2 coordination site,17 while in
heme centers it binds in the axial position, trans to the O2
binding site.
Received: December 13, 2019
https://dx.doi.org/10.1021/acs.inorgchem.9b03633
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Scheme 1. Synthesis of [Fe2 ] and [Fe2 ]
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Article
S
O
Scheme 2. Dioxygen Reactivity of the Fe−Thiolate Complexes Discussed Depends on the Presence of Protons (Simplified
Representation)
O
We recently reported a study on a dinuclear FeII−thiolate
dimers ([FeIII2(LS)2O], [Fe2 ], and [FeIII2(LS)2(OH)]+,
[Fe2OH]+, starting from [Fe2 ] and [Fe2SH]+, respectively; see
Schemes 1 and 2). Finally, through density functional theory
(DFT) calculations, we have investigated the O2 activation
S
complex, [FeII (LS)(LSH)]BF4 ([Fe2SH]+, LS2− = 2,2′-(2,2′-
2
bipyridine-6,6′-iyl)bis(1,1-diphenylethanethiolate), Scheme 1),
active for proton-assisted O2 reduction catalysis, whose
selectivity varies as a function of the experimental conditions.
Hydrogen peroxide is the main product in the presence of a
chemical reducing agent, whereas water is the major product
under electrochemical conditions.31 The peculiarity of this
complex is the presence of an unusual metal-bound thiol
group, proposed to be involved in proton relay during catalysis
and to be responsible for the reaction bifurcation.
S
mechanism of [Fe2 ] and compared the structure, thermody-
namics, and mechanistic scenarios with those reported for the
SH +
protonated counterpart [Fe2
] as well as the previously
reported analogous MnII complexes.33,34
RESULTS
■
Synthesis and Crystal Structure of the FeII-Thiolate
S
In the present work, we describe the reactivity with dioxygen
Dimer [Fe2 ]. The previously reported dimercapto-bridged
of the [Fe2SH]+ complex in the absence of additional protons,
FeII dinuclear complex [FeII (LS)(LSH)]BF4 ([Fe2SH]+)
2
and of the parent deprotonated complex [FeII (LS)2] ([Fe2 ]).
S
2
displayed an unusual metal-bound thiol. This complex was
obtained by reacting the LS2− ligand35 with Fe(BF4)2·6H2O
(1.2 equiv) in tetrahydrofuran under inert atmosphere.31 In the
We investigate the mechanism of the O2 activation process and
evaluate the role of the metal-bound thiol present only in
[Fe2SH]+. The full characterization of [Fe2 ] is also reported
S
SH
+
present work, [Fe2
]
was deprotonated to afford the
dimercapto-bridged FeII dimer [FeII (LS)2] ([Fe2 ]) in the
S
together with its redox properties. The electrochemical
oxidation of both dimercapto-bridged FeII complexes results
in the oxidation of both sulfur and metal with the formation of
two previously reported complexes in equilibrium:32 the
2
presence of NaH in MeCN.
S
The single-crystal X-ray diffraction structure of [Fe2 ],
shown in Figures 1 and S1 (crystallographic data with bond
distances and angles in Tables S1 and S2 of the Supporting
Information, respectively), displays two crystallographically
disulfide complex [FeII (LSSL)]2+ ([Fe2SS]2+, (LSSL)2−
=
2
disulfide form of the LS2− ligand) and the complex
[FeIII(LS)(MeCN)]+ ([FeMeCN]+). Remarkably, in the pres-
independent, but chemically identical, [FeII (LS)2] dimers.
2
ence of O2, the iron-bound thiolates of [Fe2SH]+ and [Fe2 ] are
S
Both units (A and B) display a quasi-planar28 diamond core
(deviations from the S2Fe1AS3Fe2A and S2Fe1BS3Fe2B
planes are less than 0.2 and 0.1 Å, respectively). The two
iron sites are not equivalent, with each FeII center being
unreactive toward O2. However, the iron(II) ions react with O2
by an inner sphere mechanism, affording rare examples of
thiolate-ligated unsupported μ-oxo and μ-hydroxo bridged FeIII
B
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quasi-reversible oxidation at E1/2 = −0.58 V vs Fc+/Fc (ΔEp =
110 mV). Bulk electrolysis at −0.50 V of an acetonitrile
S
solution of [Fe2 ] (corresponding to an exchange of
approximately one electron per iron atom) results in a mixture
of two species, i.e., the mononuclear [FeIII(LS)(MeCN)]+
([FeMeCN]+) and the dinuclear [FeII (LSSL)]2+ ([Fe2SS]2+,
2
(LSSL)2− = disulfide form of the LS2− ligand) in a 2:1 ratio.
The same mixture, called Feox for the sake of simplicity, was
previously generated by electrochemical oxidation of the
protonated complex, [Fe2SH]+, and its physical properties
were investigated earlier.31
S
Comparing the CVs of [Fe2 ] with those of [Fe2SH]+ leads to
S
the conclusion that protonation of [Fe2 ] induces notable
redox changes. More specifically, the oxidation becomes
irreversible after protonation of the dimer, with a 330 mV
S
positive shift in Epa compared to that of [Fe2 ] (−0.19 V and
S
Figure 1. Molecular structure of [Fe2 ]·0.5CH3CN·0.75Et2O
determined by single-crystal X-ray diffraction. The thermal ellipsoids
of the metal cores are drawn at 30% probability level. All hydrogen
atoms and solvent molecules are omitted for clarity.
−0.52 V, respectively). A similar shift of 300 mV was observed
for the Mn-based complexes ([Mn2 ] and [Mn2SH]+). The
S
S
substitution of Mn for Fe in [M2 ] induces a shift of about
−130 mV for the “M2 /M2III” redox process (E1/2 = −0.58 V
II
for Fe vs E1/2 = −0.45 V for Mn),33 similar to that observed
between the [Mn2SH]+ and [Fe2SH]+ complexes.
pentacoordinated and surrounded by an N2S3 donor set in a
distorted square pyramidal geometry (τ5 = 0.44 for Fe1A/τ5 =
0.44 for Fe2A and τ5 = 0.46 for Fe1B/τ5 = 0.43 for Fe2B).36 In
each dimeric unit, the two Fe−Sterminal distances are
comparable (e.g., Fe1A−S1A = 2.3382(15) Å and Fe2A−
S4A = 2.3632(17) Å), in agreement with the presence of two
terminally bound thiolates, and in contrast to what is observed
in [Fe2SH]+ (Fe1−S1 = 2.3566(11) Å and Fe2−S4(thiol) =
2.5387(11) Å).31 The loss of the intramolecular S−H···S
hydrogen-bond interaction present in [Fe2SH]+ leads to a slight
increase of the Fe···Fe distance (3.2179(13) and 3.2544(12) Å
for the two crystallographically independent molecules vs
3.1107(7) Å in [Fe2SH]+) as well as an increase of the S···S
distance (5.060 and 4.816 Å for the two crystallographically
S(H) 0/+
Reaction of [Fe2
]
with O2. The reactivity of the
[Fe2 ] and [Fe2SH]+ complexes with dioxygen, in the absence
or presence of protons (2,6-lutidinium, LutH+), is summarized
in Scheme 2. When a dilute (∼0.1 mM) green solution of
S
S
[Fe2 ] in acetonitrile is exposed to air or O2 at room
temperature, the color changes rapidly to brown. The UV−vis
absorption spectrum of the final product displays an absorption
band at 455 nm (ε ≈ 8600 M−1·cm−1), that can be assigned to
a thiolate → FeIII charge transfer band,32,37 and a shoulder at
535 nm (Figure 3). The 1H NMR spectrum at 298 K identifies
independent molecules of [Fe2 ] vs 3.594 Å in [Fe2SH]+).
Redox Properties of [Fe2 ]. The signal at 1291.2 m/z in
S
S
the electrospray ionization mass (ESI-MS) spectrum of an
S
acetonitrile solution of [Fe2 ] is assigned to the sodium adduct
of [FeII (LS)2] (Figure S2, Supporting Information) and
2
S
suggests that [Fe2 ] mostly remains dinuclear in solution. The
cyclic voltammogram (CV, see Figure 2) of [Fe2 ] shows a
S
S
Figure 3. UV−vis absorption spectrum of [Fe2 ] (0.1 mM, 1 cm path
length, scan every 0.5 s) in acetonitrile before (red) and after over
time (to violet) injection of O2.
two characteristic paramagnetically shifted signals at 14.65 and
21.11 ppm (Figure 4). Based on these features, the iron−
oxygen species generated has been assigned as the μ-oxo
bridged FeIII dimer [(FeIII2(LS)2O] ([Fe2 ]). Indeed, this
O
structure has been proposed previously as the product of the
reaction of the chloride adduct [FeIII(LS)Cl] with Bu4NOH.35
In this latter report, the assignment was based on UV−vis
absorption and NMR spectroscopic data alone. Here, the
presence of an isosbestic point at 617 nm (see Figure 3) is
S
O
consistent with the direct conversion from [Fe2 ] to [Fe2 ]
without detectable intermediates (i.e., intermediates were not
detected even when the experiments are carried out at low
temperature up to −40 °C).
Figure 2. CVs of 0.5 mM solutions (MeCN, 0.1 M Bu4NClO4) of
S
[Fe2 ] (red line) and [Fe2SH]+ (black line). GC working electrode,
100 mV·s−1.
C
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S
Figure 4. (a) UV−vis spectra (0.1 mM, 1 cm path length) and (b) 1H NMR (500 MHz) spectra of [Fe2SH]+ (black), [Fe2 ] (red), [Fe2O] (violet),
[Fe2OH]+ (green), and Feox (blue) in CH3CN/CD3CN ( indicates the main species).
■
O
Here, we were able to isolate [Fe2 ] from the reaction
donor set in two distinct geometries, i.e., in distorted square-
pyramidal (τ5 = 0.33 for Fe1) and trigonal bipyramidal (τ5 =
0.59 for Fe2) environments.36 The Fe−O distances (Fe1−O1
= 1.780(7) Å, Fe2−O1 = 1.803(8) Å) and Fe1−O1−Fe2 angle
S
between [Fe2 ] and O2 in good yield (81%) and to resolve its
structure by single crystal X-ray diffraction (Figure 5a),
confirming the previous assignment. In the structure, both
Fe centers are pentacoordinated and surrounded by a N2S2O
(145.1(5)°) are in the reported ranges for μ-oxo di-FeIII
57
̈
complexes. The zero-field powder Fe Mossbauer spectrum
recorded at 80 K (Figure 5b) displays a single doublet (δ =
0.42 mm·s−1, line width Γexp = 0.39 mm·s−1, and ΔEQ = 1.22
mm·s−1) typical of high-spin (S = 5/2) FeIII ions.
ESI mass spectrometry and Raman spectroscopy with 16O2
and 18O2 were carried out to identify the origin of the oxygen
O
atom. The ESI mass spectrum of [Fe2 ] (generated in situ in
MeCN) shows a signal at 1323.2 m/z, corresponding to the
potassium adduct of [(Fe2(LS)2O] (Figure 6a). When the
complex is synthesized from 18O2, the corresponding 18O-
labeled compound is observed in the ESI mass spectrum with
the expected shift of +2, thus demonstrating that a single
oxygen atom of O2 is incorporated into the complex and that
the μ-oxo bridge derives from dioxygen. Consistent with these
O
data, the powder Raman spectrum of [Fe2 ] (λexc = 633 nm,
Figure 6b) shows a band at 804 cm−1 that downshifts to 771
cm−1 for the 18O-labeled compound, i.e., an isotopic shift of
Δν = 33 cm−1. This band can be assigned to an Fe−O−Fe
stretch vibration,38 based on the calculated isotopic shift (Δν =
37 cm−1 using a two atom approximation) and on previously
reported data on μ-oxo-bridged diiron complexes. The DFT-
O
calculated vibrational frequencies of the [Fe2 ] complex match
those obtained from experiment well, namely, 813 cm−1, being
predicted for the vibration due to the Fe−16O−Fe stretching
mode (see the Supporting Information).
Addition of air to the thiol-containing [Fe2SH]+ complex in
acetonitrile leads to the formation of a new stable species
observed by UV−vis absorption spectroscopy (Figure 7). The
ESI-MS spectrum of the generated product displays a single
peak at 1285.3 m/z (Supporting Information, Figure S3)
O
corresponding to the protonated form of [Fe2 ]. Consistently,
1
the UV−vis and H NMR spectra of this monoxygenated
adduct (see Figure 4) match those obtained by addition of 1
equiv of LutH+ to [Fe2 ] (Figure 8). These experiments
O
demonstrate that the reaction of [Fe2SH]+ with O2 affords the
O
protonated form of [Fe2 ]. DFT calculations propose that the
protonation occurs on the bridging oxygen atom (resulting in a
hydroxo-bridged complex [FeIII2(LS)2(OH)]+, i.e., [Fe2OH]+)
rather than on the thiolate. The UV−vis absorption spectrum
Figure 5. Solid state characterization of [Fe2O]: (a) Molecular
structure (thermal ellipsoids of the metal core drawn at 10%
probability level, hydrogen atoms omitted for clarity) and (b) zero-
O
57
̈
field Fe Mossbauer spectrum (80 K).
of [Fe2OH]+ differs from that of [Fe2 ], with only one thiolate
D
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S
Figure 8. UV−vis spectra of [Fe2O] (generated from 0.1 mM [Fe2 ]
with O2 in MeCN, 1 cm path length, scan every 1 s) in MeCN before
(violet) and after addition of 1 (green) and 2 (blue) equiv of LutH+.
weaker antiferromagnetic coupling between the two ferric ions
in Fe2OH]+.39−41
While both [Fe2 ] and [Fe2OH]+ are stable in acetonitrile in
O
the absence of protons, they react instantaneously with LutH+.
Indeed, the addition of 2 and 1 equiv of LutH+ to acetonitrile
solutions of [Fe2 ] and [Fe2OH]+, respectively, leads to the
O
quantitative formation of Feox as indicated by the presence of
two isosbestic points: one at 486 nm for the conversion of
O
OH +
[Fe2 ] into [Fe2
] and the second at 502 nm for the
conversion of [Fe2
speciation behavior is observed when the addition of proton(s)
]
into Feox (Figure 8).32 The same
OH +
S(H) 0/+
occurs before exposing [Fe2
]
to dioxygen (Figure S6).
The conversion of [Fe2 ] into Feox occurs through two well-
separated steps, corresponding to the successive additions of
one proton as indicated by the overall NMR and UV−vis data.
Mechanistic Investigation. DFT calculations were then
performed to gain insight into the mechanistic details of the O2
O
activation processes by [Fe2 ] and [Fe2SH]+. Individual
S
structures along the proposed mechanism (Schemes 3−5)
S
Figure 6. (a) Experimental and simulated ESI-MS ([(Fe2(LS)2OK]+
were calculated for the reaction initiated with [Fe2 ] using two
S
peak, MeCN) and (b) Raman spectra of [Fe2O] generated from [Fe2 ]
different models that differ from their size but give comparable
results. Only thermodynamic data obtained with the larger
model are discussed in the text.
and either 16O2 or 18O2.
S
The [Fe2 ] optimized geometry matches the crystallo-
graphically determined structure shown in Figure 1 well with
similar Fe−Sterminal distances of 2.381/2.372 Å. In the
computational structure, the two iron centers are further
apart than seen in the crystal (3.469 Å calculated versus
3.2179(13)−3.2544(12) Å in the crystal), which is probably
due to the fact that the calculations were run in the gas phase.
Changing the density functional from B3LYP to BLYP gives
little change to the Fe−Fe distance and reduces it slightly to
3.454 Å, and therefore, the calculations show little sensitivity to
the choice of the density functional method.
The paradigm mechanism for dioxygen activation by diiron
complexes implies the coordination of O2 to one of the metal
1
S
Figure 7. UV−vis absorption spectra of [Fe2SH]+ (0.1 mM, 1 cm path
length, scan every 1 s) in MeCN before (black) and after (green)
injection of O2.
sites to afford a superoxo intermediate. In the case of [Fe2 ],
DFT calculations predict the formation of a dinuclear FeIIFeIII-
superoxo species, [Fe2OO•], with the superoxo terminally
bound to one Fe ion (see Scheme 3). The strongly endergonic
character of this step (ΔG = +27.3 kcal·mol−1) is comparable
with the first O2-activation step for the protonated form of the
complex, [Fe2SH]+ (ΔG = +21.0 kcal·mol−1).
→ FeIII CT transition (at 458 nm, ε ≈ 10 800 M−1·cm−1) and
1
the paramagnetically shifted signals in the H NMR spectrum
between −6.26 and 19.69 ppm (Figure 4). The larger width of
Subsequently, [Fe2OO•] evolves into a trans-μ-1,2-peroxo
diiron(III) complex, [Fe2OO] (see Scheme 3). The highly
exergonic character of the second step for the formation of the
1
O
the paramagnetic H NMR peaks in [Fe2OH]+ vs [Fe2 ] is
consistent with a stronger paramagnetism, as expected for a
E
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Scheme 3. First Steps of the Dioxygen Activation Process with [Fe2 ] (Top) and [Fe2SH]+ (Bottom) Predicted by DFT
S
a
Calculations
a
S
Energies in red are in kcal·mol−1 relative to [Fe2 ] + O2 (or [Fe2SH]+ + O2) for the (small) and [large] models and are calculated at the UB3LYP/
BS2//UB3LYP/BS1+ZPC level in Gaussian.
O
Scheme 4. Two Possible Reaction Pathways for the Conversion of [Fe2OO] to [Fe2 ] Either as a Dismutation Reaction (Top)
a
or As a Comproportionation Process with the Reactant (Bottom)
a
Reaction free energies (ΔG0, kcal·mol−1) have been calculated using DFT at the BLYP/BS2//BLYP/BS1 level of theory for the (small) and
[large] models.
[Fe2OO] intermediate (−14.7 kcal·mol−1 vs only −2.2 kcal·
mol−1 for the formation of the protonated counterpart
[Fe2OO/SH]+) is proposed to drive the entire reaction process
and thus should overcome the thermodynamically uphill first
step. The most stable structure of the peroxo complex consists
of an unsupported trans-μ-1,2 peroxo dinuclear FeIII unit. It
notably differs from the structure calculated for the reaction of
[Fe2SH]+ with O2 (see Scheme 3):31 [Fe2OO/SH]+ was found to
be less symmetric, with a rare μ-η1:η2-peroxo coordination
mode. The protonation state of the iron−peroxo intermediate
has thus an important effect on its structure, with a potential
impact on its reactivity. Unsupported peroxo dinuclear FeIII
complexes have been predominantly characterized with heme
subunits.42 In the case of non-heme dinuclear FeIII peroxo
complexes, they mainly display the cis-μ-1,2 coordination
mode in the presence of one or more additional bridges (e.g.,
carboxylate, phenolato) to stabilize such species.43−45 The
report of the first unsupported dinuclear trans-μ-1,2 peroxo
FeIII complexes from O2 and non-heme FeII complexes has
been recently published and the complex contains the
(S2SiMe2)2− ligand.46 Such unsupported peroxo species with
a trans-μ-1,2 coordination mode has been also isolated and
fully characterized from the reaction of a mononuclear MnII-
thiolate complex with O2,47 demonstrating that the presence of
thiolates can help in the stabilization of such species.
We then considered the generation of the μ-oxo bridged Fe
O
dimer [Fe2 ] from the μ-peroxo bridged Fe dimer [Fe2OO], for
which two possible mechanistic scenarios were tested (Scheme
4):42,48 (i) the dismutation of two [Fe2OO] complexes to afford
O
two molecules of [Fe2 ] and O2 (pathway A), and (ii) the
S
reaction between [Fe2OO] and the initial reactant [Fe2 ] to
O
afford two molecules of [Fe2 ] through a comproportionation
process (pathway B). Both pathways are strongly exergonic
with close values of −91.0 and −84.0 kcal mol−1, respectively,
precluding conclusions being drawn as to the preferred
pathway.
For both pathways, the cleavage of the O−O bond of
[Fe2OO] is required. When calculating the evolution of the
peroxo [Fe2OO] intermediate via O−O rupture, the exergonic
formation of a bis μ-oxo bridged FeIV dimer, [Fe2(O)2] is
predicted (Scheme 5). This type of species is definitively
accepted in the literature with a number of such highly active
F
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Scheme 5. Breaking of the O−O Bond in [Fe2OO] Is
Regarding the O2 activation pathway, DFT calculations
a
predict a similar process for the fully deprotonated [FeII (LS)2]
Predicted to Afford the [Fe2(O)2] Intermediate
2
and the thiol-containing [FeII (LS)(LSH)]+ complexes. The
2
main difference arises from the structure of the FeIII−peroxo
intermediate, with the presence of the thiol inducing a loss of
symmetry in the Fe2O2 moiety. Interestingly, this process is
different from that proposed for the analogous manganese
complexes.33 While for Mn the mechanism includes a
comproportionation step involving the starting complex and
a MnIV bis μ-oxo adduct, in the Fe system the final product is
predicted to be generated by dismutation of two FeIII−peroxo
complexes.
As found in the active site of enzymes that activate O2 with a
non-heme Fe center, in the present system, the O2 binding site
is in the cis position with respect to a thiolate ligand. While
such enzymes are involved in the oxygenation of the metal-
bound thiolate, here such reactivity is not observed. It can thus
be concluded that the binding mode of O2 with respect to the
thiolate position cannot be strictly correlated to S-centered
reactivity.
a
S
Energies in red are in kcal·mol−1 relative to [Fe2 ] + O2 for the
(small) and [large] models and are calculated at UB3LYP/BS2//
UB3LYP/BS1+ZPC in Gaussian.
intermediates fully characterized in different environments.49
In the case of the isostructural Mn-thiolate complex,33 the
corresponding bis μ-oxo bridged MnIV dimer ([Mn2(O)2]) was
stable enough to be isolated and fully characterized. It was
shown experimentally that the dinuclear μ-oxo MnIII complex
forms through subsequent comproportionation. Indeed,
depending on the experimental conditions (temperature,
relative concentrations between the complex and O2), either
the dinuclear di-μ-oxo MnIV complex or the dinuclear μ-oxo
MnIII complex is generated. In the case of the Fe system, we
were unable to trap and characterize the dinuclear di-μ-oxo
FeIV complex, [Fe2(O)2], despite many attempts. Besides, in
pursuit of experimental evidence for the dismutation process,
EXPERIMENTAL SECTION
■
General. [Fe2SH]BF4 was synthesized as previously reported,31 and
all other reagents were used as received. Acetonitrile was distilled over
CaH2 and degassed prior to use. The synthesis and isolation of [Fe2 ]
S
was carried out under argon (in a glovebox with less than 5 ppm of
O2). The infrared spectra were recorded on a Thermo Scientific
Nicolet iS10 FT-IR spectrometer (equipped with ATR accessory) as
neat solids. 1H NMR spectra were recorded on Bruker Avance III 500
MHz spectrometers. The elemental analyses were carried out with a
C, H, N analyzer (SCA, CNRS). The ESI-MS spectra were registered
on a Bruker Esquire 3000 Plus or Amazon speed ion trap
spectrometer equipped with an electrospray ion source (ESI). The
samples were analyzed in positive ionization mode by direct perfusion
in the ESI-MS interface (ESI capillary voltage= 2 kV, sampling cone
voltage= 40 V). The electronic absorption spectra were recorded on a
ZEISS MC5601 absorption spectrophotometer in quartz cells (optical
path length: 1 cm).
S
the reaction between [Fe2 ] and a mixture of 16O2 and 18O2
was monitored by GC-MS of the headspace of the reaction
vessel. Indeed, a peak at m/z = 34 assigned to 16O18O evolved,
but its intensity was barely higher than that in a blank
experiment. Hence, the results of these experiments were
inconclusive. However, due to the lack of evidence for a di-μ-
oxo FeIV dimer, we propose that [Fe2 ] is more likely
O
generated through the dismutation pathway (Scheme 4,
pathway A). Similarly, we also did not succeed in observing
the protonated form of the bis μ-oxo FeIV complex, i.e.,
[Fe2(O)2/SH]+.31 Consequently, we propose that a dismutation
process also occurs between two protonated peroxo complexes
([Fe2OO/SH]+) to generate [Fe2OH]+.
S
Synthesis of [FeII(LS)]2 ([Fe2 ]). Solid NaH (60% in mineral oil,
8.0 mg, 0.200 mmol) was suspended in MeCN (8 mL) at 293 K, and
the powder of [Fe2SH]BF4 (28.0 mg, 0.020 mmol) was added under
stirring. The color of the reaction mixture turned from brown to green
with time. After 10 min, the excess NaH was filtered off. X-ray suitable
S
dark-green crystals of [Fe2 ]·0.5CH3CN·0.75Et2O (14 mg, 0.010
mmol, 57%) were obtained by slow diffusion of diethyl ether into the
green filtrate at 293 K. ESI-MS (CH3CN, m/z,): 1291.2,
[Fe2(LS)2Na]+. 1H NMR (CD3CN, 500 MHz): δ 51.10, 34.25,
−1.25.
CONCLUDING REMARKS
■
In this work, we report the inner-sphere reactivity of the
thiolate-based dinuclear Fe complex, [FeII (LS)2], with O2.
2
Synthesis of [(FeIII2(LS)2O] ([Fe2O]). Dry dioxygen (3 mL, 1 atm)
Depending on the number of proton equivalents, the final Fe-
based product varies. When the reaction occurs in the absence
of protons or in the presence of 1 equiv of proton, an
unsupported μ-oxo or μ-hydroxo FeIII dinuclear complex is
isolated, respectively. The addition of a second proton leads to
the generation of a mixture of “oxygen-free” complexes, i.e., a
disulfide FeII dinuclear complex and a thiolate FeIII
mononuclear complex, with the concomitant release of a
water molecule. In no case, however, has cysteine oxygenase
activity with sulfur oxygenation been observed.
S
was injected into a green solution of [Fe2 ], prepared as described
above (starting from the same amounts of reactants and directly used
before the crystallization step), under stirring. The solution turned
from green to brown, and a brown precipitate was formed after a few
minutes. After 10 min, the precipitate was separated by filtration,
washed with CH3CN (5 mL), dried, and collected as a brown powder
([Fe2O], 15.3 mg, 0.012 mmol, 58%). Anal. Calcd for
C76H60N4S4Fe2O·0.2MeCN·4.2H2O: C, 67.02; H, 5.08; N, 4.30.
Found: C, 66.97; H, 4.99; N, 4.33. IR (cm−1): 1599 (s), 1571 (m),
1488 (s), 1469 (m), 1442 (s), 1314 (vw), 1271 (w), 1184 (w), 1159
(vw), 1083 (s), 1026 (m), 808 (w), 791 (vw), 746 (s), 696 (vs), 666
(m), 651 (m), 622 (m), 600 (m), 585 (w). ESI-MS (CH3CN, m/z):
1307.2, [Fe2(LS)2ONa]+, 1323.2, [Fe2(LS)2OK]+. 1H NMR
(CD3CN, 500 MHz): δ 21.11, 14.65. X-ray suitable black single
crystals of [Fe2O] were obtained by slow diffusion of diethyl ether into
a solution of the product in DMF/MeCN (1:1) at 293 K.
The detection of a μ-hydroxo FeIII dinuclear complex is not
trivial, since it is known that the acidity of a bridging hydroxide
increases with the iron oxidation state.50 For example,
protonation of the thiolate-containing μ-oxo FeIII dimer
reported by the group of Kovacs29 leads to the direct release
of water, without transient formation of a μ-hydroxo FeIII
dimer.
S
X-ray Crystallography. Single-crystal diffraction data for [Fe2 ]·
0.5CH3CN·0.75Et2O were measured on an Nonius-Bruker 4 circles
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Inorg. Chem. XXXX, XXX, XXX−XXX

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Article
diffractometer with a APEXII CCD detector and an Incoatec high
brilliance microsource with multilayer mirrors to monochromatize the
Mo Kα radiation (λ = 0.71073 Å) at 200 K. Eval, Sadabs, and Xprep
(Nonius-Bruker) were used for cell refinements, integration,
absorption correction, and data reduction. Single-crystal diffraction
data for [Fe2O] were collected at beamline Gemini151 of the ESRF
synchrotron (Grenoble, France) using a Dectris Pilatus 6 M detector
and a Maatel 2 circles Mini-diffractometer at 100 K with a toroidal Si
111 mirror monochromator at λ = 0.7293 Å. Integration of the data
was performed using the XDS Package.52 Absorption correction and
scaling were performed with Sadabs and Xprep. Subsequent steps
were run under Olex2 for the two complexes: the molecular structures
relative energies between models 1 and 2 are obtained though. We
employed two different unrestricted density functional methods,
namely, UBLYP60,61 and UB3LYP,61,62 for geometry optimizations
and frequencies: all geometries were fully minimized without
constraints in antiferromagnetic spin states. Initial geometry
optimizations and frequencies were performed with a double-ζ
quality LANL2DZ basis set on Fe (with core potential) and 6-31G*
on the rest of the atoms: basis set BS1.63,64 Energies were improved
by single point calculations utilizing a triple-ζ quality LACV3P+ basis
set on Fe (with core potential) and 6-311+G* on the rest of the
atoms: basis set BS2. Finally, a single point calculation with a
polarized continuum model included with a dielectric constant
mimicking acetonitrile was done at the BLYP/BS2 level of theory.65
Raman and vibrational frequencies were calculated in Gaussian 09
from an analytical frequency calculation, and unscaled values are
reported here unless otherwise mentioned.
S
of [Fe2 ]·0.5CH3CN·0.75Et2O was solved by charge flipping methods
and refined on F2 by full matrix least-squares techniques using the
SHELXL package.53 For [Fe2O], we decided not to refine the solvents
using a mask procedure and cctbx to refine instead of SHELXL; it has
sense from a physical point of view since there are solvent channels
inside the crystal and a dynamical disorder inside them preventing the
solvents molecules to be set properly. All non-hydrogen atoms were
refined anisotropically for the three complexes. All hydrogen atoms
were set geometrically and constrained to ride on their carrier atoms.
Raman Spectroscopy. Raman spectra at 632.8 nm (12 mW at
source, Cobolt Lasers, typically 0.15 mW at sample) using an
Olympus BX51 uptight microscope and 50× long working distance
objective. The excitation light was passed through a polarizing beam
splitter, and the power was controlled via a half wave plate and second
polarizing beam splitter. The light was directed into the optical path
using a dichroic filter, and the Raman scattering was collected through
a long pass filter to reject the Rayleigh line. The Raman scattering was
focused into a multicore fiber (100 μm, round) to line arrangement
and feed into a Shamrock163 spectrograph with an effect slit of ca. 70
μm onto an idus-416 CCD camera (Andortechnology). Data were
recorded using Solis (Andor Technology) with spectral calibration
performed using the Raman spectrum of polystyrene.54 Spectral
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.inorgchem.9b03633.
■
sı
Crystal data, bond lengths, and angles; X-ray crystal
structure; ESI-mass spectra; UV−vis spectra; optimized
structures; absolute energies of antiferromagnetic states
of complexes; relative energies; group spin densities;
B3LYP/BS1 calculated IR spectra; characterization of
frequencies in IR and Raman spectra (PDF)
Cartesian coordinates (PDF)
Accession Codes
CCDC 1971656−1971657 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
analysis was carried out using the program Spectragryph.55
57
̈
̈
Mossbauer Spectroscopy. Fe Mossbauer spectra were
recorded with a 57Co source in a Rh matrix using an alternating
̈
constant acceleration Wissel Mossbauer spectrometer operated in the
transmission mode and equipped with a Janis closed-cycle helium
cryostat. Isomer shifts are given relative to iron metal at ambient
temperature. Simulation of the experimental data was performed with
the Mfit program using Lorentzian line doublets: E. Bill, Max-Planck
AUTHOR INFORMATION
Corresponding Authors
■
Marcello Gennari − Univ. Grenoble Alpes, CNRS UMR 5250,
DCM, F-38000 Grenoble, France; orcid.org/0000-0001-
5205-1123; Email: marcello.gennari@univ-grenoble-alpes.fr
Sam P. de Visser − Manchester Institute of Biotechnology and
Department of Chemical Engineering and Analytical Science,
The University of Manchester, Manchester M1 7DN, United
Kingdom; orcid.org/0000-0002-2620-8788;
Institute for Chemical Energy Conversion, Mulheim/Ruhr, Germany.
̈
Electrochemistry. Electrochemical experiments were performed
in CH3CN solution under an argon-saturated atmosphere (in a
glovebox with less than 5 ppm of O2). The supporting electrolyte
tetrabutylammonium perchlorate (Bu4NClO4) was used as received
and stored in glovebox. Cyclic voltammetry and controlled potential
electrolysis experiments were carried out by using a PGSTAT100N
Metrohm-Autolab potentiostat/galvanostat. A standard three-elec-
trode electrochemical cell was used. Potentials were referred to a Ag/
0.01 M AgNO3 reference electrode in CH3CN + 0.1 M Bu4NClO4,
and measured potentials were calibrated through the use of an
internal Fc/Fc+ standard. The working electrode was a vitreous
carbon disk (3 mm in diameter) polished with 2 μm diamond paste
(Mecaprex Presi) for cyclic voltammetry (Ep,a, anodic peak potential;
Epc, cathodic peak potential; E1/2 = (Epa + Epc)/2; ΔEp = Epa − Epc).
Exhaustive electrolysis was carried out on reticulated vitreous carbon
electrode 45 PPI (the electrosynthesis Co. Inc.; 1 cm3). The auxiliary
electrode was a Pt wire in CH3CN + 0.1 M Bu4NClO4.
Email: sam.devisser@manchester.ac.uk
Carole Duboc − Univ. Grenoble Alpes, CNRS UMR 5250,
DCM, F-38000 Grenoble, France; orcid.org/0000-0002-
9415-198X; Email: carole.duboc@univ-grenoble-alpes.fr
Authors
Lianke Wang − Institutes of Physical Science and Information
Technology, Anhui University, 230601 Hefei, Anhui, P. R.
China; Univ. Grenoble Alpes, CNRS UMR 5250, DCM, F-
38000 Grenoble, France
Computational Details. All calculations were performed using
previously described methods56,57 using density functional theory as
implemented in the ORCA and Gaussian 09 program packages.58,59
́
Fabian G. Cantu Reinhard − Manchester Institute of
́
Biotechnology and Department of Chemical Engineering and
Analytical Science, The University of Manchester, Manchester
M1 7DN, United Kingdom
S
We investigated the oxygen activation by dinuclear [Fe2 ]. Some
calculations used a simplified model (starting from the previously
described structural properties of [Mn2SH]+)33 that has all phenyl
substituents replaced by methyl, model 1, while the full system is
model 2. A detailed study at the B3LYP level of theory for model 1
has been performed and covers a range of different electronic and spin
states for several complexes. No major differences in structure and
Sandeep K. Padamati − Univ. Grenoble Alpes, CNRS UMR
5250, DCM, F-38000 Grenoble, France; Molecular Inorganic
Chemistry, Stratingh Institute for Chemistry, Faculty of Science
and Engineering, University of Groningen, 9747AG Groningen,
The Netherlands
H
https://dx.doi.org/10.1021/acs.inorgchem.9b03633
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Article
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David Flot − ESRF European Synchrotron 71, 38000 Grenoble,
France
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ChemBioChem 2006, 7, 1536−1548.
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Wesley R. Browne − Molecular Inorganic Chemistry, Stratingh
Institute for Chemistry, Faculty of Science and Engineering,
University of Groningen, 9747AG Groningen, The
Netherlands; orcid.org/0000-0001-5063-6961
Franc Meyer − Institute of Inorganic Chemistry, University of
̈
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Gottingen, D-37077 Gottingen, Germany; orcid.org/0000-
0002-8613-7862
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.inorgchem.9b03633
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
The authors gratefully acknowledge research support of this
work by the China Scholarship Council (L.W.), the French
National Agency for Research in the framework of the
“Investissements d’avenir” program (ANR-15-IDEX-02), the
Labex ARCANE, the CBH-EUR-GS (ANR-17-EURE-0003),
the ANR-DFG (ANR-16-CE92_0012_01), the Deutsche
Forschungsgemeinschaft (DFG Me1313/14-1, NiFeMim),
the COST Action CM1305 (EcostBio) especially via the
STSM 34962, and The Netherlands Ministry of Education,
Culture and Science (Gravity Program 024.001.035 to
W.R.B.), and the allocation of beam time for the experiment
at the ID23-1 beamline at the European Synchrotron Radiation
Facility − ESRF, Grenoble. F.G.C.R. thanks the Conacyt
Mexico for a studentship.
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