Dioxygen activation by a dinuclear thiolate-ligated Fe(ii) complex

Article abstract of DOI:10.1039/C8DT04491K

Dioxygen activation by Fe^II thiolate complexes is relatively rare in biological and chemical systems because the sulfur site is at least as vulnerable as the iron site to oxidative modification. O₂ activation by Fe^II-SR complexes with thiolate bound trans to the O₂ binding site generally affords the Fe^IV═O intermediate and oxidized thiolate. On the other hand, O₂ activation by Fe(ii)-SR complexes with thiolate bound cis to the O₂ binding site generates Fe^III-O-Fe^III or S-oxygenated complexes. The postulated Fe^IV═O intermediate has only been identified in isopenicillin N synthase recently. We demonstrated here that O₂ activation by a dinuclear Fe^II thiolate-rich complex produces a mononuclear Fe^III complex and water with a supply of electron donors. The thiolate is bound cis to the postulated dioxygen binding site, and no Fe^III-O-Fe^III or S-oxygenated complex was observed. Although we have not detected the transient intermediate by spectroscopic measurements, the Fe^IV═O intermediate is suggested to exist by theoretical calculation, and P-oxidation and hydride-transfer experiments. In addition, an unprecedented Fe^III-O₂-Fe^III complex supported by thiolates was observed during the reaction by using a coldspray ionization time-of-flight mass (CSI-TOF MS) instrument. This is also supported by low-temperature UV-vis measurements. The intramolecular NHO═Fe^IV hydrogen bonding, calculated by DFT, probably fine tunes the O₂-activation process for intramolecular hydrogen abstraction, avoiding the S-oxygenation at cis-thiolate.

Full text of DOI:10.1039/C8DT04491K

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Dioxygen activation by a dinuclear thiolate-ligated
Fe(II) complex†
Cite this: Dalton Trans., 2019, 48,
379
Chang-Chih Hsieh,a Yu-Chiao Liu,b Mei-Chun Tseng,b Ming-Hsi Chiang b and
Received 12th November 2018,
Accepted 26th November 2018
a
Yih-Chern Horng
*
DOI: 10.1039/c8dt04491k
rsc.li/dalton
Dioxygen activation by FeII thiolate complexes is relatively rare in with a mononuclear active site, Fe-superoxo, -peroxo or high
biological and chemical systems because the sulfur site is at least valent oxo complexes have been implicated as reactive inter-
as vulnerable as the iron site to oxidative modification. O2 acti- mediates.2 In such an oxidizing environment, cysteine (Cys) is
vation by FeII–SR complexes with thiolate bound trans to the O2 thought to be an inappropriate coordinating ligand because
binding site generally affords the FeIVvO intermediate and oxi- the sulfur site is at least as vulnerable as the iron site to oxi-
dized thiolate. On the other hand, O2 activation by Fe(II)–SR com- dative modification. Cytochrome P450 and NO synthase rep-
plexes with thiolate bound cis to the O2 binding site generates resent the only examples of heme-containing enzymes for the
FeIII–O–FeIII or S-oxygenated complexes. The postulated FeIVvO activation of dioxygen with Cys residue ligation.3 In the well-
intermediate has only been identified in isopenicillin N synthase studied cytochrome P450, Cys coordinates axially and facili-
recently. We demonstrated here that O2 activation by a dinuclear tates the heterolytic O–O bond cleavage of the FeIII–OOH inter-
FeII thiolate-rich complex produces a mononuclear FeIII complex and mediate to produce an FeIVvO species.4 The other thiolate-
water with a supply of electron donors. The thiolate is bound cis to ligating Fe enzymes, for example cysteine dioxygenase (CDO)5
the postulated dioxygen binding site, and no FeIII–O–FeIII or and isopenicillin N synthase (IPNS),6 enable thiolate binding
S-oxygenated complex was observed. Although we have not cis to the O2 binding site on the substrate prior to O2 activation
detected the transient intermediate by spectroscopic measurements, and substrate oxidation. The postulated FeIVvO catalytic inter-
the FeIVvO intermediate is suggested to exist by theoretical calcu- mediate of these enzymes7 was detected in IPNS only recently.8
lation, and P-oxidation and hydride-transfer experiments. In Delicate control over S oxidation is governed by these Fe
addition, an unprecedented FeIII–O2–FeIII complex supported by enzymes, particularly those enzymes with a nonheme active
thiolates was observed during the reaction by using a coldspray site. There is a lack of thorough understanding, and this is an
ionization time-of-flight mass (CSI-TOF MS) instrument. This is also interesting process to explore. Relatively rare non-heme FeII thio-
supported by low-temperature UV-vis measurements. The intra- late complexes employed for inner-sphere O2 activation have
molecular NH⋯OvFeIV hydrogen bonding, calculated by DFT, prob- been reported, where the reaction has only generated
ably fine tunes the O2-activation process for intramolecular hydro- S-oxygenated9 or FeIII–O–FeIII complexes.10 Besides, whether O2-
gen abstraction, avoiding the S-oxygenation at cis-thiolate.
mediated generation of S-oxygenated products [Fe–S(O)xR]
(x = 1, 2, or 3) is Fe(II) based O2-capture or not still remains
elusive.11 Here we report O2 activation by dinuclear FeII thiolate-
rich complex 1 with NNS ligands (LNHS−) in the presence of
(LNHS)2 to produce a mononuclear FeIII complex (2), a 1,2-benz-
isothiazolin-3-one derivative12 (LN-S), and H2O (Scheme 1). The
reaction mechanism of this process and the observation of an
FeIII–O2–FeIII intermediate are also described.
Introduction
Dioxygen activation for the preparation of an oxidized organic
substrate through a redox reaction is generally utilized by iron
metalloenzymes.1 During the catalytic cycles of these enzymes
aDepartment of Chemistry, National Changhua University of Education,
Changhua 50058, Taiwan. E-mail: ychorng@cc.ncue.edu.tw
bInstitute of Chemistry, Academia Sinica, Taipei 11528, Taiwan, Republic of China
†Electronic supplementary information (ESI) available: Additional spectroscopic
and single-crystal data. CCDC 1838290 (1), 1838291 (2), 1838292 [(LNHS)2] and
1838293 (LN-S). For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c8dt04491k
Experimental
General procedures
Commercially available chemicals were purchased from
Aldrich or Acros, and used as received. The organic compound,
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electrodes. Cyclic voltammograms were obtained from solu-
tions containing
1 mM analytes in DMF using 0.1 M
[n-Bu4N][PF6] as the supporting electrolyte. Elemental analyses
and MS spectrometry were performed on a Heraeus CHN-OS
Rapid Elemental Analyzer and JEOL JMX-SX/SX 102A Mass
Spectrometer at the Instruments Center of National Chung
Hsing University, Taiwan.
Synthesis of (LNHS)2. The synthesis procedure of (LNHS)2 is
the same as the published report.15 1H NMR (300 MHz,
d6-DMSO, 25 °C): δ 9.31 (2H, t), 8.54 (2H, d), 8.03 (2H, d), 7.78
(2H, t), 7.69 (2H, d), 7.48 (2H, t), 7.43 (2H, d), 7.35 (2H, t), 7.28
(2H, t), 4.61 (4H, d). The only product (LNHS)2 with no trace of
LN-S was obtained when LNHSH or LNHS− was stirred in
DMSO at 90 °C for 3 h. The air-stable yellow crystals of
(LNHS)2 suitable for X-ray crystallographic analysis were
obtained by layering the THF solution with pentane at 4 °C for
1 week.
Scheme 1 Summary of the reactions for the syntheses of complexes 1,
2, LN-S, and reduction of O2 to H2O.
Preparation of 1. A solution of [Et4N][HFe(CO)4] (0.3 g,
1.0 mmol) and (LNHS)2 (0.97 g, 2.0 mmol) in CH3CN (20 mL)
was stirred at room temperature overnight under a N2 atmo-
2,2′-dithiobenzoyl chloride, was prepared under aerobic con- sphere. THF was added to the resulting solution (50 mL) to
ditions.13 The inorganic compound [Et4N][HFe(CO)4] was syn- afford yellow precipitates. The precipitates were collected with
thesized under anaerobic conditions by following the pub- a filter, washed with THF (15 mL) three times and dried under
lished procedures14 and stored in a N2-filled glovebox. The vacuum to afford 1 (yield: 0.3 g, 55%). The yield was calculated
syntheses of iron complexes were performed under a dry nitro- from the number of Fe moles of [Et4N][HFe(CO)4] divided by
gen atmosphere according to standard Schlenk techniques or the number of Fe moles of 1. The air-unstable yellow crystals
performed in a glove box. All solvents except for DMSO were of 1 suitable for X-ray crystallographic analysis were obtained
distilled, dried, and stored in N2-filled reservoirs containing by layering the yellow MeCN solution of 1 with ether at room
4 Å molecular sieves before use. THF and hexane were distilled temperature for 1 week. IR (KBr): 3419 (w; νN–H), 1610, 1525 (s,
under nitrogen using sodium–benzophenone as a drying νCvO) cm−1; UV/Vis (DMF) [λmax, nm (ε, M−1 cm−1)]: 361
reagent. Ether and DMF were distilled under nitrogen using (18 540); anal. calcd for: C 57.57, H 4.09, N 10.33; found: C
CaH2 as a drying reagent. Dichloromethane was distilled 57.70, H 4.46, N 9.95.
under nitrogen using P2O5 as a drying reagent. DMSO was
Synthesis of 2. A solution of [Et4N][HFe(CO)4] (0.31 g,
purged under nitrogen and then stored in dried N2-filled reser- 1.0 mmol) and (LNHS)2 (1.02 g, 2.1 mmol) in CH3CN (25 mL)
voirs containing 4 Å molecular sieves. 1H, 13C and 31P NMR was stirred at room temperature overnight under a N2 atmo-
spectra were obtained on an Avance 300 spectrometer. sphere. The resulting yellow solution was changed to a dark-
Chemical shifts for 1H and 13C{1H} spectra were recorded in green solution immediately by exposure to oxygen. The dark-
ppm relative to the residual proton and 13C of CDCl3 green solution was further stirred in air for 8 h. The solution
(1H: δ 7.24; 13C: δ 77.0) and DMSO-d6 (1H: δ 2.50; 13C: δ 39.5). was then filtered and concentrated to 10 mL under vacuum
UV-vis spectra were obtained on a GBC 202 spectrophotometer, and ether (35 mL) was added to precipitate the products. The
while infrared spectra were recorded on a Bruker Alpha instru- upper solution was removed using a cannula, and the dark-
ment using ZnSe discs (0.2 mm, KBr windows). The low- green precipitates were dried under vacuum to afford 2 (yield:
temperature UV-vis spectra were obtained with an Agilent 8453 0.37 g, 66%). The dark-green crystals of 2 suitable for X-ray
spectrophotometer. The UV cell was loaded with 0.1 mM of 1 crystallographic analysis were obtained by layering the MeCN
in DMF and cooled to 0 °C or −50 °C, and O2 was injected to solution with ether at room temperature for
1 week.
the solution. The coldspray ionization time-of-flight mass Alternatively, complex 2 can be obtained from 1 and (LNHS)2
(CSI-TOF MS) spectral data were collected on a JMS-T100CS in CH3CN. Pure O2 (2.3 mL, 0.1 mmol) was injected to a solu-
(JEOL) mass spectrometer equipped with a CSI source. Typical tion containing pure 1 (0.11 g, 0.1 mmol) and (LNHS)2 (0.05 g,
measurement conditions are as follows: needle voltage, 0 kV; 0.1 mmol) in CH3CN (25 mL) and the solution was stirred at
orifice current, 50–500 nA; orifice voltage, 0 to 20 V; ring lens room temperature for 4 h. 20% tetraethylammonium hydrox-
voltage, 30 V; and spray temperature, −50 °C. EPR spectra were ide aqueous solution (0.15 g, 0.2 mmol) was added to the
monitored at X-band frequencies by using a Bruker EMSplus above solution and stirred for 10 min. The resulting solution
spectrometer with an 8″ magnet and 2.7 kW power supply. was concentrated to 5 mL under vacuum and ether (40 mL)
Electrochemical measurements were performed with
a
was added to precipitate the products. The upper solution was
CH-611C electrochemical analyzer utilizing 3 mm glassy removed using a cannula, and the dark-green precipitates were
carbon working, Ag/AgCl reference, and platinum auxiliary dried under vacuum to afford 2 (yield: 0.098 g, 72%). IR (KBr):
380 | Dalton Trans., 2019, 48, 379–386
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1514 (s, νCvO) cm−1; UV/Vis (CH3CN) [λmax, nm (ε, M−1 cm−1)]: Computational details
361 (4370), 454 (1900), 571 (960), 721 (320); anal. calcd for: C
60.27, H 5.98, N 10.65; found: C 60.04, H 5.77, N 10.40.
DFT calculations were performed on the Gaussian 03
program.16 Geometry optimizations were conducted using the
BP86 functional and 6-31G** basis sets. The spin states of the
intermediates A and B, and complex 1 were assigned as S = 0.
The spin states of the intermediate C and the transition state
(TS) were assigned as S = 2. The spin state of the intermediate
D was assigned as S = 1. The spin states of complex 2 were
assigned as S = 1/2 supported by EPR measurements.
Synthesis of 2-(pyridin-2-ylmethyl)benzisothiazol-3(2H)-one
(LN-S). The resulting green solution for the synthesis of
complex 2 in DMSO was dried under vacuum at 60 °C to afford
a dark green mixture. The dark green powder was dissolved in
DMF, and dark green and yellow crystals were obtained by
layering the DMF solution with ether at room temperature for
2 weeks. The yellow crystals of LN-S were collected for X-ray
crystallographic analysis and other analyses. 1H NMR Crystallography
(300 MHz, CDCl3, 25 °C): δ 8.55 (1H, d), 8.03 (1H, d), 7.62 (1H,
The crystals suitable for structure analysis were mounted on a
t), 7.56 (1H, t), 7.85 (1H, d), 7.36 (1H, t), 7.27 (1H, d), 7.18 (1H,
d), 5.14 (2H, s). 13C NMR: δ 165.33, 155.68, 140.57, 137.02,
131.88, 126.71, 125.40, 123.95, 122.86, 122.45, 120.31, 49.00.
1H NMR (300 MHz, d6-DMSO, 25 °C): δ 8.54 (1H, d), 7.96
(1H, d), 7.91 (1H, d), 7.78 (1H, t), 7.68 (1H, t), 7.44 (1H, t), 7.31
(1H, t), 7.29 (1H, d), 5.12 (2H, s). 13C NMR: δ 164.94, 155.03,
147.82, 141.17, 139.68, 132.36, 126.00, 125.86, 123.92, 123.73,
123.08, 122.21, 47.22. IR (KBr): 1658 (s, νCvO) cm−1. Anal. calcd
for: C 64.44, H 4.16, N 11.56; found: C 64.31, H 3.69, N 11.53.
glass fiber with silicone grease and placed in the cold stream
of a Bruker APEX II with graphite monochromated Mo Kα radi-
ation (λ = 0.71073 Å) at 150(2) K. All structures were solved by
direct methods using SHELXS-97 and refined by full-matrix
least squares methods against F2 with SHELXL-97.17 Tables of
neutral atom scattering factors, f′ and f″, and absorption coeffi-
cients are from a standard source.18 All atoms except for hydro-
gen atoms were refined with anisotropic displacement para-
meters. In general, hydrogen atoms were fixed at calculated
positions, and their positions were refined using a riding
model. Crystallographic data collection and refinement para-
meters are given in Table S0.†
In situ NMR experiment for complex 1 reacting with oxygen
In a glove-box, a mixture of pure 1 (0.022, 0.02 mmol) and
(LNHS)2 (0.010 g, 0.02 mmol) in d6-DMSO (15 mL) was stirred
at room temperature overnight, and the overnight solution was
transferred to a J. Young NMR tube. After collecting the first
NMR spectrum of the overnight solution, the J. Young NMR
Results and discussion
tube was degassed with a vacuum system and filled with The isolation of 1 was determined based on early reports.19
oxygen gas to conduct the in situ NMR experiment.
Treatment of two equiv. of (LNHS)2 with [HFe(CO)4]− in
CH3CN at RT led to the generation of 1 with the liberation of
LNHSH and LNHS− via the formation of the intermediates
In situ NMR experiment for (LNHS)2 reacting with oxygen
A solution of (LNHS)2 (0.003 g) dissolved in d6-DMSO (0.4 mL) [(LNHS)Fe0(CO)4]− and fac-[(LNHS)3FeII(CO)3]−. Subsequent
in air was transferred to a J. Young NMR tube for in situ NMR dimerization occurs with a release of all carbon monoxide
experiment.
moieties. The yellow complex 1 (55% yield) in the solid state is
stable for weeks and transforms into a green species gradually
within months in air. The crystal structure of 1 was studied
Preparation of oxygenated complex 1 for IR measurement
A solution of 1 (0.022 g) in DMF (5 mL) at −50 °C was injected using X-ray diffraction, and the molecular structure is shown
with limited excess O2 and stirred for 1 min. Ether (50 mL) was in Fig. 1 (selected bond lengths and angles in Table S1, ESI†).
added to the green solution to precipitate the oxygenated
Complex 1 has an inversion center in the middle of two
complex 1. The upper solution was removed using a cannula, metal ions. Each six-coordinated FeII ion is ligated by two
and the green precipitates were collected and dried under LNHS− and they are bridged by two thiolato-S donors. Each
vacuum for solid IR experiment.
FeII ion is coordinated by three thiolato sulfurs, two nitrogens
from pyridino and amido moieties, and one carbonyl oxygen.
A distal pyridine arm is pointing away from each iron site in
P-Oxidation experiment
4 equiv. of PPh3 and 1 equiv. of complex 1 were loaded into a both halves of the dimer. The structure of the di-iron(II) core in
flask prior to adding DMF (20 ml) in a glove box. The mixture in 1 is significantly different from several reported complexes
the flask was exposed to air for 20 min, and the solution was with similar FeII–FeII(μ-SR)2 motifs (Table S2, the ESI†).10a,20
transferred to an NMR tube to conduct 31P {1H} NMR experiment. The relatively long Fe⋯Fe (3.548 Å), short S⋯S (3.490 Å), and
long averaged Fe–Sbridged (2.488 Å) distances in 1 indicate that
Hydride-transfer experiment
complex 1 tends to dissociate into mononuclear fragments in
4 equiv. of 9,10-dihydroanthracene and 1 equiv. of complex 1 solution. A one-step oxidation or reduction process in cyclic
were loaded into a flask prior to adding DCM (20 ml) in a voltammetry analyses (Fig. S1, ESI†) and the detection of
glove box. The mixture in the flask was exposed to air for monomeric 1 in the coldspray ionization time-of-flight mass
30 min, and the solution was loaded into a microtube for high (CSI-TOF MS) spectrum (Fig. S11, ESI†) also suggested the
resolution mass spectrometry analysis.
existence of mononuclear 1 in solution. Interestingly, hydro-
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Fig. 2 ESI-MS spectrum of the solution containing pure 1 and one equiv.
of (LNHS)2 exposed to oxygen for synthesizing complex 2 in DMSO.
ducts as determined by electronspray ionization mass spec-
trometry (ESI-MS) (Fig. 2). However, 1 without adding (LNHS)2
in DMSO supplied with a slight excess of O2 consecutively for
at least 2 h at RT afforded EPR-silent species. The initial green
solution gradually turned yellow with the detection of
−
LNHSO3 (m/z 291.0) and no trace of 2 by ESI-MS after 5 h
(Fig. 3). Therefore, the organic ligand (LNHS)2 must exist for
the formation of 2 during the reaction between 1 and O2. The
molecular structure of 2 (Fig. 1, bottom) was obtained success-
fully and the selected bond lengths and angles are listed in
Table S3, ESI.† Two similar Fe–S, Fe–N(amido) or Fe–N(pyri-
dino) bond distances indicate that the two ligands contribute
to the electron density equally on the iron ion. The hydrogens
of the carboxamido NH moieties disappeared in 2. The X-band
EPR spectrum of 2 in 50% DMSO aqueous solution at 77 K dis-
plays an axial signal with g values at 2.19 and 1.95 (Fig. S3, the
ESI†), indicating the low-spin nature of the FeIII center with
an asymmetric coordination environment in solution. The
Fig. 1 ORTEP diagrams of 1 (top) and 2 (bottom) with thermal ellipsoids
with 50% probability. The NH⋯S intramolecular hydrogen bond inter-
actions are shown as dashed lines, and the cation in 2 and hydrogen
atoms bound to carbon atoms have been omitted for clarity.
gen in the Fe-bound carboxamido NH moiety has an intra-
molecular NH⋯S hydrogen bond interaction with the terminal
thiolato sulfur bound on the other iron. The N⋯S contact dis-
tance of 3.379 Å is comparable to those of other complexes
with hydrogen-bond interactions.21 In addition, the inter-
molecular NH⋯N hydrogen bond interactions utilizing carbox-
amido NH and pyridino nitrogen on the distal pyridine arm
were revealed to occur between molecules forming the 1D
polymer (Fig. S2, ESI†).
Interestingly, when a solution containing pure 1 and one
equiv. of (LNHS)2 was exposed to oxygen in CH3CN, the solu-
tion color changed immediately from yellow to dark-green. 2
was isolated from the solution with 72% yield. Due to the low
solubility of 1 in CH3CN, the studies of the reaction process
during the transformation of 1 into 2 were performed in
DMSO or DMF. The reaction of 1 and limited O2 in the pres-
Fig. 3 ESI-MS spectrum of pure 1 without adding (LNHS)2 reacted with
ence of (LNHS)2 in DMSO shows no trace of S-oxygenation pro- a slight excess of O2 in DMSO for 5 h.
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FeIII–O–FeIII or S-oxygenated species that were observed in the transient green species with a half-life of 2.5 and 5 h at RT,
similar O2-activation by FeII–SR complexes were not found in respectively. It is known that the typical metal-bound sulfinate
the O2-activation by 1.
(–SO2) and sulfenate (–SO) stretches are in the range of
respectively. This
The in situ 1H NMR experiments in d6-DMSO were 1000–1150 cm−19d,22 and 900–1000 cm−1 23
,
employed to monitor the reaction process during the trans- green species show no obvious peak corresponding to sulfur
formation of 1 into 2 in the presence of (LNHS)2. The chemical oxidation in either range from solid IR measurements (Fig. S7,
shifts of pure complexes 1 and 2 were not observed in d6- ESI†). Thus, the possibility of this species derived from the
DMSO due to the inherent paramagnetism. Therefore, the S-oxygenated reaction can be exclusively ruled out. As shown
1
peaks that appeared in the in situ H NMR spectra correspond in Fig. 5, the reaction of 1 with a slight excess of O2 led to the
to the chemicals without Fe complexes. As expected, the initial appearance of three new absorption bands at λmax = 460 nm,
reaction mixture contained mostly (LNHS)2 before being 570 nm, and 670 nm for the green species, and they decayed
exposed to dioxygen. After the reaction proceeded for 2 h, the gradually after 20 h. The reactivity of 1 with O2 at −50 °C nearly
intensity of the peak corresponding to the chemical shift of mirrored that at RT except for the apparent absorption at 730 nm,
water (δ 3.40 ppm) increased with time, and the intensity of and this green chromophore (λmax = 570 nm, and 730 nm) was
the chemical shifts corresponding to (LNHS)2 (CH2 at stable for at least 5 h at this low temperature (Fig. 6). The absorp-
δ 4.60 ppm) decreased with the generation of a benzisothiazol- tion band with λmax at 570 nm (ε ∼ 2300 M−1 cm−1) is assigned to
3(2H)-one derivative (LN-S, CH2 at δ 5.11 ppm) simultaneously
(Fig. S4, ESI†). It was known that (LNHS)2 or LNHSH cannot
be oxidized in DMSO to generate LN-S even in the presence of
oxygen with 90 °C reflux for 5 days (see Fig. S5, ESI.† The X-ray
structures of (LNHS)2 and LN-S are shown in Fig. S6, ESI†).
1
Thus, from the H NMR experiments, (LNHS)2 acts as an elec-
tron donor driving the reaction of 1 and O2 to form 2 and H2O.
Without the addition of (LNHS)2, the reaction product of 1 and
O2 gradually decomposed and S-oxygenated species were
−
formed as evidenced by the detection of LNHSO3
.
The delay of LN-S formation (∼5 h) during the O2 activation
process using pure 1 and (LNHS)2 in DMSO at RT provides an
opportunity to explore the nature of possible intermediates.
Actually, pure 1 in DMSO supplied with a slight excess of O2 in
the presence of 5 equiv. of ferrocene produced 2 within 1 min,
which was confirmed by EPR (Fig. 4). This implies that the
electron-transfer reaction is the rate-limiting step for the pro-
duction of H2O and 2. In good correlation with the EPR
Fig. 5 UV-vis spectral changes for the reaction of 1 with a limited
results, UV-vis spectra revealed that 1 with and without excess of O2 in DMSO at RT, leading to the formation of an FeIII–O2–FeIII
intermediate. The inset shows the time-dependent increase and
decrease of the absorption band at 570 nm. The decaying curves are
(LNHS)2 in DMSO reacting with O2 initially yielded the same
shown in Fig. S8, ESI.†
Fig. 6 UV-vis spectral changes for the reaction of 1 with a limited
Fig. 4 X-band EPR spectra of pure 1 in DMSO after adding an excess of
O2 at various time points in the absence and presence of ferrocene at
room temperature.
excess of O2 in DMF at −50 °C, leading to the formation of an FeIII–O2–
FeIII intermediate. The inset shows the time-dependent increase of the
absorption band at 730 nm.
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the sulfur-to-Fe(III) charge transfer band and the one with λmax at
730 nm (ε ∼ 1900 M−1 cm−1) is very similar to those observed in
the reported FeIII–O2–FeIII complexes with N- and O-based
ligands.24 CSI-TOF MS analysis at −50 °C also suggested the
formation of an FeIII–O2–FeIII product, as shown by the peak at
m/z 1139 (Fig. S9, ESI†). The HRMS data along with the isotopic
distribution pattern (Fig. S10, ESI†) can correspond to an ion with
the composition of [1 + O2 + Na]+, identical to the FeIII–O2–FeIII
intermediate with the sodium ion. To our knowledge, this is
the first time the FeIII–O2–FeIII complex with thiolate ligation is
detected. Attempts to obtain suitable crystals of the green
species for X-ray characterization have been unsuccessful so far.
To detect other intermediates in the 1-mediated O2 acti-
vation process, the oxygenation of 1 was conducted in the pres-
ence of ferrocene at 0 °C and monitored using a UV-vis
spectrometer. However, no new peak can be obviously
observed except for the formation of 2 (Fig. 7). P-Oxidation,
S-oxidation and hydride-transfer experiments using PPh3,
PhSMe, and 9,10-dihydroanthracene, respectively, were con-
ducted to test the existence of the intermediate with the
FeIVvO functional group in the reaction process.2d,25 This
green species converted 30% PPh3 to OvPPh3 after 20 min
(Fig. S12, ESI†) and anthracene was detected by high resolu-
tion mass spectrometry (HRMS) after 30 min (Fig. S13, ESI†).
However, the green species did not react at all with MeSPh at
RT. The results indicate the involvement of an FeIV oxo species
in the oxygenation process. The FeIVvO intermediate is prob-
ably too transient to be detected using an UV-vis spectrometer
at 0 °C.
Scheme 2 Proposed reaction mechanism for O2 activation by 1.
as the transition state (TS), were also calculated. The reaction
mechanism (Scheme 2) and the energy diagram (Fig. 8) are
shown. The mononuclear FeII resulting from the partial dis-
sociation of dimeric 1 provides a vacant site for oxygen
binding,26 and an O2 molecule can insert into the di-iron(II)
core of 1 to form A or B. The intermediate A (−43.8 kcal mol−1
)
is more energy-favorable than B (−4.5 kcal mol−1). It is inter-
esting to note that the oxygen atoms of the bound peroxide in
A have intramolecular hydrogen bond interactions with the
hydrogens of the coordinated carboxamido NH groups
(Fig. S14, ESI†). The FeIVvO intermediate C is generated
further by homolytic cleavage of the O–O peroxide bond.
Although there are rare examples of FeIV–OH species in the
In order to gain insight into the reaction process, density
functional theory (DFT) calculation was used to examine the
possible candidates. The optimized geometries of the two FeIII
intermediates with two oxygen atoms (A: end-on conformation;
B: side-on conformation) were initially evaluated, and the
ironIV-oxo (C) and ironIV-hydroxide (D) intermediates, as well
nonheme system reported,27
D
with an FeIV–OH group
(−80.7 kcal mol−1) is more stable than C (−51.8 kcal mol−1) in
Fig. 7 Time-dependent UV-vis spectra of oxygenation of 1 in the pres-
ence of two equiv. of ferrocene in DMF at 0 °C (pure 1: black line; the
first time point of 1 exposed to O2: red line). After the addition of oxygen
to 1, the absorption bands at 570 and 730 nm were increased immedi-
ately and decreased by time to form 2. The inset shows the time-depen-
dent increase and decrease of the absorption band at 730 nm.
Fig. 8 BP86/6-31G** free-energy profile for oxygen activation from
complex 1 to form complex 2 and water. All structures are simplified as
Fe atom with bonded atoms, and the atoms with different colors indi-
cate that the atoms belong to different ligands.
384 | Dalton Trans., 2019, 48, 379–386
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our DFT calculation results. The carboxamido hydrogen in
close contact with the oxygen in the FeIVvO motif facilitates
the formation of D by intramolecular hydrogen transfer, and
this prediction was supported by the low activation energy of
the TS (Fig. S15, ESI†). Thus, hydrogen bonding in
NH⋯OvFeIV favors intramolecular hydrogen abstraction and
avoids S-oxygenation at cis-thiolate.28 Consecutively, after the
hydroxyl group of intermediate D abstracts a proton in the
unbound amide to form water dissociated from iron, and the
FeIV center obtains an electron from the organic ligand
(LNHS)2, 2 is formed by structural rearrangement.
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In conclusion, we have shown that a dimeric FeII complex with
NNS chelating ligands, Fe2(LNHS)4 (1), is capable of activating
dioxygen through an inner-sphere mechanism to form water
with a supply of electron donors. Although the crystal structure
has not been obtained, the FeIII–O2–FeIII species is detected to
be the essential intermediate during the reaction. In addition,
the FeIV oxo species is suggested as a transient intermediate
evidenced by P-oxidation and hydride-transfer experiments.
Under limited excess O2 conditions, the intramolecular
NH⋯OvFeIV hydrogen bonding probably fine tunes the O2-
activation process, thus avoiding S-oxygenation at cis-thiolate.
Conflicts of interest
There are no conflicts to declare.
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Acknowledgements
We gratefully acknowledge the financial support from the
Ministry of Science and Technology of Taiwan (MOST 106-
2113-M-018-007 to Y.-C. H.).
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