Iron Hydride Detection and Intramolecular Hydride Transfer in a Synthetic Model of Mono-Iron Hydrogenase with a CNS Chelate

Article abstract of DOI:10.1021/acs.inorgchem.5b01733

We report the identification and reactivity of an iron hydride species in a synthetic model complex of monoiron hydrogenase. The hydride complex is derived from a phosphine-free CNS chelate that includes a Fe-C^NH(=O) bond (carbamoyl) as a mimic of the active site iron acyl. The reaction of [(^O=C^HNN^pyS^Me)Fe(CO)₂(Br)] (1) with NaHBEt₃ generates the iron hydride intermediate [(^O=C^HNN^pyS^Me)Fe(H)(CO)₂] (2; δ_Fe-H = -5.08 ppm). Above -40 °C, the hydride species extrudes CH₃S^- via intramolecular hydride transfer, which is stoichiometrically trapped in the structurally characterized dimer μ₂-(CH₃S)₂-[(^O=C^HNN^Ph)Fe(CO)₂]₂ (3). Alternately, when activated by base (^tBuOK), 1 undergoes desulfurization to form a cyclometalated species, [(^O=C^NHNC^Ph)Fe(CO)₂] (5); derivatization of 5 with PPh₃ affords the structurally characterized species [(^O=C^NHNC)Fe(CO)(PPh₃)₂] (6), indicating complex 6 as the common intermediate along each pathway of desulfurization.

Full text of DOI:10.1021/acs.inorgchem.5b01733

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Iron Hydride Detection and Intramolecular Hydride Transfer in a
Synthetic Model of Mono-Iron Hydrogenase with a CNS Chelate
†
†
Gummadi Durgaprasad, Zhu-Lin Xie, and Michael J. Rose*
Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, United States
*
S Supporting Information
ABSTRACT: We report the identification and reactivity of an iron hydride species in a synthetic model complex of monoiron
NH
hydrogenase. The hydride complex is derived from a phosphine-free CNS chelate that includes a Fe−C (O) bond
O HN py Me
(
carbamoyl) as a mimic of the active site iron acyl. The reaction of [(
C
N S )Fe(CO) (Br)] (1) with NaHBEt generates
2
3
O HN py Me
the iron hydride intermediate [(
C
N S )Fe(H)(CO) ] (2; δ
= −5.08 ppm). Above −40 °C, the hydride species
2
Fe−H
−
extrudes CH S via intramolecular hydride transfer, which is stoichiometrically trapped in the structurally characterized dimer μ -
3
2
O HN Ph
t
(
CH S) -[(
C
N )Fe(CO) ] (3). Alternately, when activated by base ( BuOK), 1 undergoes desulfurization to form a
3
2
2 2
O NH
C NC )Fe(CO) ] (5); derivatization of 5 with PPh affords the structurally characterized species
2 3
Ph
cyclometalated species, [(
O NH
C NC)Fe(CO)(PPh ) ] (6), indicating complex 6 as the common intermediate along each pathway of desulfurization.
3 2
[
(
he enzyme monoiron hydrogenase (HMD) catalyzes a
reduction has spurred the synthesis of structural models of a
3
4
T
hydride transfer from dihydrogen (H ) to tetrahydrome-
HMD active site by Hu et al. and Song et al., as well as
2
+
5
thenylmethanopterin (H MPT ), which serves as a C carrier
during the methanogenic reduction of carbon dioxide (CO ).
functional studies by Meyer et al.
4
1
1
2
One key intermediate in the catalytic cycle has been
6
This metalloenzyme (also called Hmd: H MPT dehydrogen-
proposed as an iron(II) hydride, although such a species has
4
ase) plays an obligate role in the metabolism of CO to
not yet been detected in any enzymatic study. Thus, the
identification and study of such a reactive species is of keen
interest. Recent reports in the iron catalysis literature contain
2
methane (CO → CH ) in the absence of bioavailable nickel
2
4
(
i.e., in the absence of [NiFe] hydrogenase). Although there are
other H -activating enzymes, there are no other known
2
several examples of H activation and hydride transfer, wherein
2
biological examples of H activation by a mononuclear iron
2
the catalytically active iron(II) is supported by ligation of one
or two carbonyl ligands. The reported hydride transfer catalysts
likely proceed through intermediates analogous to a putative
fac-{Fe(H)(CO)2}+ fragment possibly encountered during
site. The active site of HMD exhibits a unique array of
nonproteinaceous ligands (Scheme 1), including the cis-
Scheme 1. Possible Mechanism of Heterolytic Splitting of H
Performed by HMD
2
enzymatic catalysis, although a concerted H cleavage
2
6
6b
mechanism is also possible. The iron dicarbonyl hydride
motif has been observed in the nonbiomimetic pincer system in
NH NH
+
7
the complex [(P
N P)Fe(H)(CO) ] . However, there are
2
+
no reports of a biomimetic, phosphine-free {Fe(H)(CO)2}
unit. Herein, we report the identification of such a complex.
In relation to the iron acyl motif found in the enzyme active
site, we have utilized the related carbamoyl ligation of type
8
{
Fe−C(O)NH}, in which the organometallic Fe−C(O)
unit is retained. Pickett and co-workers reported complexes
containing a “ferracyclic carbamoyl” unit,
9
,10
dicarbonyls and the bidentate pyridone−acyl unit, which
which served as
2
presents an organometallic Fe−C σ bond. The active site
exhibits no redox activity, and only activates H in the presence
of a substrate. The exact role of each donor moiety remains
unclear, although the dicarbonyl motif enforces a low-spin,
iron(II) configuration. The desire to develop inexpensive iron-
based catalysts for hydrogenation, hydride transfer, and CO2
2
Special Issue: Small Molecule Activation: From Biological Principles
to Energy Applications Part 3
1
Received: July 30, 2015
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.inorgchem.5b01733
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Forum Article
structural models of the active site. To provide a more robust
and stable framework for reactivity and hydride transfer studies,
the ligand used herein presents a biomimetic CNS donor set in
a single chelate. Reaction of the amino-appended N/S ligand
with [Fe(CO) (Br) ] in Et O from −25 to −5 °C generates a
Scheme 2. Reactivity of Characterized Complexes 1−3, 5,
and 6, as Well as Proposed Intermediate [4]
4
2
2
copious yellow precipitate, accompanied by vigorous extrusion
of carbon monoxide (CO) gas. Purification of this solid by
chromatography through Al O affords the carbamoyl bromide
2
3
O HN py Me
C N S )Fe(CO) (Br)] (1). The solid-state IR
2
adduct [(
of 1 exhibits ν(CO) features at 2034 and 1974 cm
−
1
−
1
(
enzyme = 2011 and 1944 cm ). Solutions of 1 in
tetrahydrofuran (THF)-d are remarkably stable in the presence
8
of air or moisture (hours to days) and exhibit features (δN−H
.96 ppm; δS−CH3 = 2.60 ppm) consistent with the ligand
coordinated to low-spin iron(II).
=
9
To emulate an iron hydride intermediate as proposed for the
enzymatic mechanism, complex 1 was treated directly with a
8
hydride source. A pale-yellow THF-d solution of 1 was mixed
1
with ∼1 equiv of NaHBEt at −70 °C. The resulting H NMR
3
spectrum obtained at −70 °C (Figure 1) exhibits a notable peak
Figure 2. ORTEP diagram (30% ellipsoids) of 3. Hydrogen atoms
except NH are omitted for clarity. Selected bond distances (Å) and
angles (deg): Fe2−C1 = 1.939(2), Fe2−N2 = 2.083(2), Fe2−S1 =
2
1
.3287(7), Fe2−S2 = 2.3679(7), Fe2−C14 = 1.751(3), Fe−C13 =
.763(3); N1−C1−O1 = 119.0(2), Fe2−C1−N1 = 109.90(17), Fe2−
C1−O1 = 130.9(2).
1
Figure 1. Variable-temperature H NMR spectra (−70 to −10 °C, 400
8
MHz) for the reaction of 1 in THF-d with ∼1 equiv of NaHBEt to
phenyl ring is twisted away from the core of the dimer. Notably,
3
NH
form the iron hydride species 2.
the Fe−C(O) carbamoyl unit [Fe−C = 1.939(2) Å] and
the cis-dicarbonyl fragments remain essentially undisturbed.
The bridging methyl thiolate units arrange the Fe−S distances
at 2.3287(7) and 2.3679(7) Å, which fixes the two iron(II) ions
at a distance of ∼3.54 Å within the Fe S diamond core. The
at −5.08 ppm, attributable to a Fe−H species. This resonance
exhibits an intermediate value compared with other reported
NH NH
P)Fe(H)(CO)2]+
N
iron(II) carbonyl hydrides, such as [(P
2
2
(
δFe−H = −7.47 ppm) and [(PNNP)Fe(H)(CO)] (δ
=
solid-state IR exhibits four red-shifted ν(CO) features at 2013,
Fe−H
7
,11
−1
−
2.25 ppm).
The Fe−H resonance is accompanied by a
1991, 1965, and 1923 cm (see the Supporting Information,
downfield shift in the NH feature to 11.66 ppm (parent 1; δ
Figure S2) due to conversion of the neutral thioether(s) to the
anionic thiolate(s). It is important to note that the conversion
from the hydride species 2 to dimeric 3 is stoichiometric,
suggesting a controlled reaction pathway of intramolecular
hydride transfer, followed by dimerization.
N−H
=
9.96 ppm). The presence of the shifted (but not absent) NH
resonance provides evidence that H2 is not eliminated,
precluding the formation of a dearomatized intermediate at
low temperature. On this basis, we assign the structure of the
O NH Py Me
iron hydride intermediate as [(
2 in Scheme 2).
The variable-temperature NMR study indicates that the
hydride species 2 is stable between −70 and −40 °C. Above
C
N S )Fe(H)(CO) ]
To investigate the possibility of the hydride acting as a base
(NH-activating agent) in the reaction, complex 1 was treated
with a strong base. The reaction of a yellow solution of 1 in
2
(
t
THF with BuOK at room temperature rapidly generates a
−
40 °C, the Fe−H resonance decreases, indicating trans-
formation to another species; this product was not readily
identified by H NMR spectroscopy. To remedy this problem, a
dark-red solution and a beige precipitate (KBr). Subsequently,
1
extraction of the product into C D6 affords a H NMR
6
1
spectrum (Figure 3, inset) indicative of a single species in
solution. The resulting stable, yellow solid exhibits a red-shifted
IR spectrum consistent with cis-dicarbonyl ligation, evidenced
THF solution of 1 was treated with ∼1 equiv of NaHBEt at
3
room temperature. Following the removal of THF and
extraction into C D , the yellow product was redissolved in
−1
by ν(CO) = 2003 and 1940 cm (Figure 3). The observation
6
6
1
fluorobenzene/pentane to afford the dimeric species μ -
of a NH proton in the H NMR spectrum of this isolated
2
O NH Ph
(
CH S) -[(
C
N )Fe(CO) ] (3) as a structurally charac-
terized complex (Figure 2). In this complex, the C −S bond
found in 1 has been cleaved, and the resulting (protonated)
species shifted upfield to 7.35 ppm (for 1, δNH = 9.96 ppm in
THF-d ), as well as the lack of a thioether resonance near δ
3
2
2 2
Ar
8
CH3
≈ 2.60 ppm and the aforementioned desulfurization, led to
B
DOI: 10.1021/acs.inorgchem.5b01733
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Inorganic Chemistry
Forum Article
the precursor [(iPr2PNHNNHPiPr2)Fe(CO) ] with zinc dust.
+
7
2
Relatedly, Milstein and Huang individually reported the
isolation of dearomatized complexes of the type [(PNP)M-
+
(
CO)(H)(L)] (M = Fe, Ru) by analogous treatment with a
12,13
base.
It was desirable to prove that the five-coordinate cyclo-
metallate 5 served as a common intermediate for both
structurally characterized products (3 and 6). As such, a THF
solution of 5 was treated with ∼1 equiv of thiophenol (PhSH)
at room temperature. Following solvent exchange to C D , the
6
6
1
H NMR spectrum (see the Supporting Information, Figure
S6) and the characteristic four-peak IR spectrum [ν(CO) =
−1
2
017, 1998, 1964, 1932 cm ; see the Supporting Information,
Figure S2] were similar to structurally characterized 3,
O NH Ph
C N )Fe(CO) ]
2 2
1
indicating the formation of μ -(PhS) -[(
Figure 3. IR and H NMR (inset) spectra for 5 in the aromatic region.
2
2
HN
py
(3′). This reaction confirms 5 as the common intermediate
IR: ν(CO) 2003, ν(CO) 1940, ν( CO) 1606, ν(CN )
t
1579.
along each pathway of desulfurization ( BuOK or NaHBEt ).
3
In conclusion, we have studied the reactivity of an iron
hydride intermediate (2) in a synthetic model of HMD. This
Fe−H species promotes C−Sthioether bond cleavage and the
formation of an iron(II) cyclometalate. However, the equatorial
arrangement of the present CNS donor set is distinct from the
facial CNS motif found in the active site. Future work will
address this issue and incorporate the biomimetic thiolate and
methylene−acyl unit to more accurately model the active site.
formulation of this species as the putative five-coordinate CNC
pincer [(
To confirm the ligand binding mode of the putative
O NH
C NC )Fe(CO) ] (5).
2
Ph
cyclometalate 5, the complex was derivatized with PPh for
3
14
structural characterization. The reaction of 5 with excess PPh3
O NH
C NC)Fe(CO)-
in benzene afforded yellow crystals of [(
PPh ) ] (6; Figure 4). Crystallographic analysis confirms (i)
(
3
2
ASSOCIATED CONTENT
Supporting Information
■
*
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.5b01733.
X-ray crystallographic data in CIF format (CIF)
Spectra and synthetic details (PDF)
AUTHOR INFORMATION
Corresponding Author
E-mail: mrose@cm.utexas.edu.
■
Figure 4. Two ORTEP views (50% ellipsoids) of 6. PPh is truncated
3
*
for clarity; all hydrogen atoms except NH are omitted for clarity.
Selected bond distances (Å) and angles (deg): Fe−C11 = 2.009(2),
Fe−C12 = 2.008(2), Fe−C13 = 1.725(2), Fe−N1 = 1.9540(18), Fe−
P1 = 2.2531(6), Fe−P2 = 2.2525(6); C11−Fe−C12 = 159.36(9),
N1−Fe−C13 = 174.36(9), P1−Fe−P2 = 174.92(3).
Author Contributions
These authors contributed equally to this work.
†
Notes
The authors declare no competing financial interest.
desulfurization of the ligand framework and (ii) concomitant
ACKNOWLEDGMENTS
cyclometalation of the former C−S(CH ) carbon directly to the
■
3
iron(II) center. Pseudooctahedral 6 again retains the Fe−C(
The authors gratefully acknowledge the Robert A. Welch
Foundation (F-1822) and the ACS Petroleum Research Fund
(PRF 53542-DN13) for financial support.
O)NH carbamoyl unit, as well as one carbonyl; the remaining
axial sites are occupied by PPh . To determine the fate of the
3
extruded sulfur unit, an analogous reaction was performed in
the presence of PMe as a [S] scavenger. Extraction of the
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