Active-site models for iron hydrogenases: Reduction chemistry of dinuclear iron complexes

Article abstract of DOI:10.1021/ic0610381

Reduction of Fe₂(μ-S₂C₃H ₆)(CO)₆ (1) in tetrahydrofuran with 1 equiv of decamethylcobaltocene (Cp*₂Co) affords a tetranuclear dianion 2. The IR spectra of samples of 2 in solution and in the solid state exhibit a band at 1736 cm^-1, suggestive of the presence of a bridging carbonyl (CO) ligand. X-ray crystallography confirms that the structure of 2 consists of two Fe₂ units bridged by a propanedithiolate moiety formulated as [Fe₂(μ-S₂C₃H₆)(CO) ₅-(SCH₂CH₂CH₂-μ-S)Fe ₂(μ-CO)(CO)₆]^2-. One of the Fe₂ units has a bridging CO ligand and six terminal CO ligands. The second subunit exhibits a bridging propanedithiolate moiety. One CO ligand has been replaced by a terminal thiolate ligand, replicating the basic architecture of Fe-only hydrogenases. The reduction reaction can be reversed by treatment of 2 with 2 equiv of [Cp₂Fe][PF₆], reforming complex 1 in near-quantitative yield. Complex 2 can also be oxidized by acids such as p-toluenesulfonic acid, regenerating complex 1 and forming H₂.

Full text of DOI:10.1021/ic0610381

Inorg. Chem. 2006, 45, 8000−8002
Active-Site Models for Iron Hydrogenases: Reduction Chemistry of
Dinuclear Iron Complexes
Inigo Aguirre de Carcer,† Antonio DiPasquale,‡ Arnold L. Rheingold,‡ and D. Michael Heinekey*,†
Department of Chemistry, UniVersity of Washington, Seattle, Washington 98195-1700, and
Department of Chemistry and Biochemistry, UniVersity of California at San Diego,
La Jolla, California 92093-0332
Received June 9, 2006
Reduction of Fe2(
µ
-S2C3H6)(CO)6 (1) in tetrahydrofuran with 1 equiv
Computational studies4 favor the latter possibility in that a
smooth pathway for heterolysis of bound H2 is possible via
proton transfer to the adjacent N atom. More recent crystal-
lographic work is also consistent with this hypothesis.5
Several model systems for this active site based on well-
studied organometallic precursors have been investigated.6
Darensbourg and co-workers reported the crystal structure
of Fe2(µ-S2C3H6)(CO)6 (1) and pointed out its close structural
resemblance to the enzyme active site.7 Rauchfuss and co-
workers have reported that reaction of 1 with CN affords
[Fe2(µ-S2C3H6)(CO)4(CN)2]2-. This dicyano species is readily
oxidized to insoluble materials.8 A very promising Fe2S3
model system that mimics the active site with a pendant
thioether moiety attached to the central C atom of a
propanedithiolate bridging ligand has been reported by
Pickett and co-workers. Interestingly, with this ligand system,
a transient bridging CO species is formed upon reaction with
CN.9 This is a very significant observation because the
existence of a bridging CO ligand in some redox states of
the enzyme has been clearly demonstrated by IR spectros-
copy.2,5 Definitive evidence for bridging CO ligands in model
complexes has been very limited, with the only isolable
complexes being isonitrile10 and cyanide11 derivatives re-
ported by Rauchfuss and co-workers. Interesting model
of decamethylcobaltocene (Cp*2Co) affords a tetranuclear dianion
2. The IR spectra of samples of 2 in solution and in the solid
state exhibit a band at 1736 cm-1, suggestive of the presence of
a bridging carbonyl (CO) ligand. X-ray crystallography confirms
that the structure of 2 consists of two Fe2 units bridged by a
propanedithiolate moiety formulated as [Fe2(
µ-S2C3H6)(CO)5-
(SCH2CH2CH2- -S)Fe2(
µ
µ
-CO)(CO)6]2-. One of the Fe2 units has
a bridging CO ligand and six terminal CO ligands. The second
subunit exhibits a bridging propanedithiolate moiety. One CO ligand
has been replaced by a terminal thiolate ligand, replicating the
basic architecture of Fe-only hydrogenases. The reduction reaction
can be reversed by treatment of 2 with 2 equiv of [Cp2Fe][PF6],
reforming complex 1 in near-quantitative yield. Complex 2 can also
be oxidized by acids such as p-toluenesulfonic acid, regenerating
complex 1 and forming H2.
Recent crystallographic studies of the iron hydrogenase
enzymes1 show that the active site contains a novel Fe2
moiety. Unidentified diatomic ligands were ultimately shown
to be carbonyl (CO) and cyanide (CN) ligands by IR
spectroscopy.2 Activation of H2 is believed to occur at a
vacant site formed by loss of weakly bound water. Inhibition
of enzymatic activity by CO binding to this site has been
demonstrated, and the structure of the CO-bound form has
been determined.3 The proposed dithiolate bridge cannot be
definitively characterized from the crystallographic data on
the enzymes. A propanedithiolate or an azapropanedithiolate
structure with a central N atom has been suggested.
(4) Fan, J.-H.; Hall, M. B. J. Am. Chem. Soc. 2001, 123, 3828-3829.
(5) Nicolet, Y.; de Lacey, A. L.; Vernede, X.; Fernandez, V. M.;
Hatchikian, E. C.; Fonticella-Camps, J. C. J. Am. Chem. Soc. 2001,
123, 1596-1601.
(6) For a summary of early work in this area, cf.: Darensbourg, M. Y.;
Lyon, E. J.; Smee, J. J. Coord. Chem. ReV. 2000, 206, 533-543. For
a more recent review, see: Liu, X.; Ibrahim, S. K.; Tard, C.; Pickett,
C. J. Coord. Chem. ReV. 2005, 249, 1641-1652.
(7) Lyon, E. J.; Georgakaki, I. P.; Reibenspies, J. H.; Darensbourg, M.
Y. Angew. Chem., Int. Ed. 1999, 38, 3178-3179.
(8) Schmidt, M.; Contakes, S. M.; Rauchfuss, T. B. J. Am. Chem. Soc.
1999, 121, 9736-9737.
(9) Le Cloirec, A.; Best, S.; Borg, S.; Davies, S. C.; Evans, D. J.; Hughes,
D. L.; Pickett, C. J. J. Chem. Soc., Chem. Commun. 1999, 2285-
2286. Razavet, M.; Davies, S. C.; Hughes, D. L.; Pickett, C. J. J.
Chem. Soc., Chem. Commun. 2001, 847-848. George, S. J.; Cui, Z.;
Razavet, M.; Pickett, C. J. Chem.sEur. J. 2002, 8, 4037-4046.
(10) Boyke, C. A.; Rauchfuss, T. B.; Wilson, S. R.; Rohmer, M.; Benard,
M. J. Am. Chem. Soc. 2004, 126, 15151-15160.
(11) Boyke, C. A.; van der Vlugt, J. I.; Rauchfuss, T. B.; Wilson, S. R.;
Zampella, G.; De Gioia, L. J. Am. Chem. Soc. 2005, 127, 11010-
11018.
* To whom correspondence should be addressed. E-mail: heinekey@
chem.washington.edu.
† University of Washington.
‡ University of California at San Diego.
(1) Clostridium pasteurianum: Peters, J. W.; Lanzilotta, W. N.; Lemon,
B. J.; Seefeldt, L. C. Science 1998, 282, 1853-1858. DesulfoVibrio
desulfuricans: Nicolet, Y.; Piras, C.; Legrand, P.; Hatchikian, C. E.;
Fontecilla-Camps, J. C. Structure 1999, 7, 13-23.
(2) Pierek, A. J.; Hulstein, M.; Hagen, W. R.; Albracht, S. P. J. Eur. J.
Biochem. 1998, 258, 572-578.
(3) Lemon, B. J.; Peters, J. W. Biochemistry 1999, 38, 12969-12973.
8000 Inorganic Chemistry, Vol. 45, No. 20, 2006
10.1021/ic0610381 CCC: $33.50
© 2006 American Chemical Society
Published on Web 09/01/2006

COMMUNICATION
Scheme 1
Figure 1. Partial IR spectra (CO stretching region) of complex 2: (a)
solid state; (b) solution in THF.
complexes with azadithiolate bridging ligands have recently
been prepared by a novel synthetic approach.12 Model
complexes with azadithiolate and phosphine ligands have
been shown to form a briding hydride and protonate at the
bridiging N atom.13
Several reports have described the reduction chemistry of
1, with somewhat conflicting results. A reversible two-
electron reduction of complex 1 in dimethylformamide under
CO was previously reported based on cyclic voltammetry
(CV) studies.14 A recent report by Darensbourg and co-
workers using CV and bulk electrolysis studies in CO-
saturated CH3CN is consistent with an initial one-electron
reduction at -1.34 V (vs NHE), with a subsequent one-
electron reduction to a dianion occurring only at -1.95 V.15
Darensbourg also reported that the reduced species led to
H2 evolution in the presence of acetic acid. Pickett and co-
workers recently reported that H2 evolution from protic media
catalyzed by complex 1 under reducing conditions is
comprised of two processes with measured onsets at -1.34
and -1.56 V.16
Pickett and co-workers also reported the detailed study of
a one-electron-reduction product formulated as 1a (see
Scheme 1) and the subsequent chemistry of this complex,
which includes a proposed disproportionation/ligand redis-
tribution reaction that affords a dimeric species containing
four Fe atoms. The structure of this molecule depicted below
as 2 was proposed based on limited spectroscopic data
because the complex could not be isolated.
Figure 2. ORTEP diagram of the anionic portion of 2 (50% thermal
ellipsoids). Selected bond distances (Å): Fe1-Fe2, 2.5075; Fe2-S4, 2.280;
Fe3-Fe4, 2.5224.
Reduction of tetrahydrofuran (THF) solutions of complex
1 with 1 equiv of Cp*2Co leads to clean formation of a new
species 2 in seconds at room temperature. Complex 2 was
isolated as the bis-Cp*2Co+ salt by the addition of diethyl
ether.17 The IR spectrum of 2 in the CO region consists of
five intense bands at 2014, 1967, 1950, 1934, and 1919 cm-1
corresponding to terminal CO ligands and one lower energy
band at 1736 cm-1 consistent with the presence of a bridging
CO group (see Figure 1).
Crystals of 2 suitable for X-ray diffraction were obtained
by filtration of the THF solution described above followed
by layering with diethyl ether.18 The structure of 2 consists
of two Fe2 units connected by a propanedithiolate bridge.
One of the Fe2 units has a bridging CO ligand and six
terminal CO ligands, while the other has five CO ligands, a
(15) Chong, D.; Georgakaki, I. P.; Mejia-Rodriguez, R.; Sanabria-
Chinchilla, J.; Soriaga, M. P.; Darensbourg, M. Y. J. Chem. Soc.,
Dalton. Trans. 2003, 4158-4163.
(16) Borg, S. J.; Behrsing, T.; Best, S. P.; Razavet, M.; Liu, X.; Pickett,
C. J. J. Am. Chem. Soc. 2004, 126, 16988-16999. Borg, S. J.; Bondin,
M. I.; Razavet, M.; Liu, X.; Pickett, C. J. Biochem. Soc. Trans. 2005,
33, 3-6.
(17) Elem anal. Calcd for C58H72Co2Fe4O12S4: C, 48.68; H, 5.08; S, 8.96.
Found: C, 48.50; H, 5.30; S, 8.99.
We report herein our studies of the chemical reduction of
1, which allows for the isolation and structural characteriza-
tion of the previously postulated complex 2.
(18) Crystal data for 2: C58H72Co2Fe4O12S4, brown plate, 20 × 20 × 5
µm, triclinic, P1 (No. 2), Z ) 2, a ) 9.163(6) Å, b ) 19.047(13) Å,
c ) 20.123(14) Å, V ) 3064(4) Å3, µ ) 1.645 mm-1, Dcalc ) 1.550
g/cm3, R1 ) 0.0467, wR2 ) 0.0890. Data collection: Bruker Smart
CCD system, T ) 100 K, Mo KR (λ ) 0.710 73 Å), 31 845 reflections,
10 761 unique reflections. The data were corrected for absorption; the
structure was solved by direct methods; all non-H atoms were refined
anisotropically by full-matrix least squares (SHELXL-97); all H atoms
were placed using a riding model and their positions constrained
relative to their parent atom.
(12) Li, H.; Rauchfuss, T. B. J. Am. Chem. Soc. 2002, 124, 726-727.
(13) Schwartz, L.; Eilers, G.; Eriksson, L.; Gogoll, A.; Lomoth, R.; Ott, S.
J. Chem. Soc., Chem. Commun. 2006, 520-521.
(14) Darchen, A.; Mousser, H.; Patin, H. J. Chem. Soc., Chem. Commun.
1988, 968-970.
Inorganic Chemistry, Vol. 45, No. 20, 2006 8001

COMMUNICATION
Scheme 2
propenedithiolate bridge, and a terminal thiolate ligand (see
Figure 2).
The structure of complex 2 is most conveniently consid-
ered in two parts, labeled as 2a and 2b in the representation
below. If we assume that each Fe dimer moiety carries a
single negative charge, then 2a consists of two formally FeI
atoms at a bond distance of 2.5075(16) Å. This Fe-Fe bond
distance and all other structural parameters in 2a are very
similar to those from X-ray crystallography for the active
site of the Fe-only hydrogenase enzymes.1 With five terminal
diatomic ligands and differential S ligation at the Fe atoms,
2a is a rare example of an anionic monosubstituted thiolate
diiron pentacarbonyl that replicates the basic architecture of
the enzyme.
rearrangement involved in the formation of 2, it is quite
surprising that these reactions are readily reversible upon
oxidation. The very rapid formation of 2 upon reduction of
1 and the facile oxidation of complex 2 to yield 1 suggest
that the electrode chemistry of 1 may also be affected by
the formation of complex 2. We find that complex 2 can
also be oxidized by p-toluenesulfonic acid (pKa ) 8 in
CH3CN),20 regenerating complex 1 and forming H2. This
observation suggests a possible role for complex 2 in the
reported electrocatalytic evolution of H2 observed in the
presence of 1.15,16
We find that reduction of the closely related bridging
azadithiolate complex Fe2(µ-SCH2NPhCH2S-µ)(CO)6 (3)
gives similar results21 (Scheme 2). Complex 3 differs from
1 in that the central CH2 moiety of the propyl bridge is
replaced with a NPh group. Reaction of 3 with Cp*Co affords
a new complex 4. The IR spectrum of 4 consists of five
intense bands at 2021, 1969, 1960, 1936, and 1920 cm-1
A complex closely related to the heptacarbonyl moiety
2b has been previously isolated by Pickett and co-
workers by reduction of 1 under CO with Li(HBEt3).16
By this procedure, a propanethiol salt [Fe2(µ-CO)(CO)6(µ-
SCH2CH2CH2SH][Li] was prepared. The spectroscopic simi-
larity of this complex to the electrode reduction product is
apparent.16 Like 2b, the Pickett complex is diamagnetic with
both Fe atoms formally in the zero oxidation state.
Complex 2 is readily oxidized using a ferricenium ion.
Thus, reaction of dianion 2 in THF with 2 equiv of
[Cp2Fe][PF6] affords complex 1. The complete reaction
sequence can be conveniently monitored by IR spectroscopy
(see the Supporting Information), which indicates a 90%
yield for the overall reaction (Scheme 1).
Rapid CO substitution reactions of hexacarbonylmetal-
bridged dimers of Co and Fe have been reported upon
chemical or electrochemical reduction.14,19 The initial reduc-
tion of these complexes populates an antibonding metal-
metal orbital; odd electron metal fragments are generated
and can be readily substituted in the presence of a suitable
ligand. Consistent with the electrochemical studies of Pickett
and co-workers, we postulate that an initial one-electron
reduction of 1 leads to a very short-lived species 1a.
Formation of 2 from 1a on the time scale observed requires
rapid substitution of a CO ligand by a thiolate and efficient
capture of the CO ligand, accompanied by electron transfer
between the Fe dimers.
1
and a bridging band at 1738 cm-1. The H NMR spectrum
of 3 exhibits aromatic resonances (10H) and aliphatic
resonances (8H) due to the methylene bridges (see the
Supporting Information). The spectroscopic data for 4 suggest
a structure similar to that of 2.
Oxidation of 4 with 2 equiv of [Cp2Fe][PF6] affords
complex 3 in 70% yield. Complex 4 can also be oxidized
by p-toluenesulfonic acid, regenerating complex 3 and H2
gas. The yield of 3 in these reactions is consistently inferior
to the yield of 1 obtained by oxidation of 2. Oxidation of 4
is accompanied by substantial decomposition reactions to
unidentified products.
We conclude that insights as to the active-site structure
of the iron hydrogenases can be gained by the study of simple
analogues such as 1, but the reduction chemistry of these
complexes is much more complicated than previously
thought. We are continuing to study related molecules with
the goal of developing efficient catalysts for the electrocata-
lytic production of H2.
Acknowledgment. We thank the donors of the Petroleum
Research Fund, administered by the American Chemical
Society, for partial support of this research. Support was also
provided by the University of Washington Royalty Research
Fund.
Supporting Information Available: Experimental details and
X-ray crystallographic data (CIF) for 2. This material is available
free of charge via the Internet at http://pubs.acs.org.
Our observations support the proposal of Pickett and co-
workers that one-electron reduction of 1 can be followed by
a rapid bimolecular disproportionation reaction accompanied
by extensive ligand redistribution. Given the extensive ligand
IC0610381
(19) Bezems, G. J.; Reiger, P. H.; Visco, S. J. J. Chem. Soc., Chem.
Commun. 1981, 265-266. Arewgoda, M.; Robinson, B. H.; Simpson,
J. J. Am. Chem. Soc. 1983, 105, 1893-1903.
(20) Izutsu, K. Acid-Base Dissociation Constants in Dipolar Aprotic
SolVents; Blackwell Scientific Publications: Oxford, U.K., 1990.
(21) Li, H.; Rauchfuss, T. B. J. Am. Chem. Soc. 2002, 124, 726-727.
8002 Inorganic Chemistry, Vol. 45, No. 20, 2006