Reversible dimerization of mononuclear models of [Fe]-hydrogenase

Article abstract of DOI:10.1002/chem.201300495

Enzyme models on the catwalk! A series of new model complexes of the active site of [Fe]-hydrogenase have been synthesized and characterized. These complexes are monomeric in solution, but dimeric in the solid state. Copyright

Full text of DOI:10.1002/chem.201300495

COMMUNICATION
DOI: 10.1002/chem.201300495
Reversible Dimerization of Mononuclear Models of [Fe]-Hydrogenase
Bowen Hu,[a] Dafa Chen,*[a] and Xile Hu*[b]
[Fe]-Hydrogenase, which can activate H2 in the presence
of methenyltetrahydromethanopterin (methenyl-H4MPT+),
is the only mononuclear hydrogenase known.[1–3] In its active
site, there are two cis-CO, a cysteine sulfur atom (Cys 176),
and a bidentate pyridinol acyl ligand (Figure 1, A).[4,5] The
coordination position trans to the acyl group is regarded as
the H2-binding position.[6]
were obtained, both in the solid state and in solution.[27]
Herein, we describe the equilibrium between the dimeric
complexes and their monomeric components in solution.
Reaction of [Fe(2-CH2CO-6-MeOC5H3N)(CO)3I] (2)[25]
with (4-NO2-C6H4)SNa gave a dinuclear complex that has a
formula of [{Fe(2-CH2CO-6-MeOC5H3N)(CO)2{S-(4-NO2-
C6H4)}}2] (3a) in the solid state, as revealed by X-ray crystal-
lography (Scheme 1). Complex 3a has a C2 symmetry
À
(Figure 2). The C2 axis passes through the midpoint of Fe1
Fe2 and is perpendicular to the plane of Fe1-S1-Fe2-S2.
Each iron ion is coordinated in an octahedral geometry by
two cis-CO, two thiolate ligands, and the acylmethylpyridin-
yl moiety. The IR spectrum of 3a in the solid state shows
four intense n(CO) absorption bands.
Figure 1. The active site structure of [Fe]-hydrogenase (A) and the pro-
posed structure of the protein-free FeGP cofactor extracted with 2-mer-
captoethanol (B).
[Fe]-Hydrogenase also contains an iron guanylylpyridinol
(FeGP) cofactor, which can be extracted by denaturation of
the enzyme in the presence of 2-mercaptoethanol.[7,8] The
protein-free cofactor is too unstable to be identified;
however, its structure was proposed based on the active site
structure of [Fe]-hydrogenase (Figure 1, B).[9–11]
Following the elucidation of the active site of [Fe]-hydro-
genase, a number of synthetic models have been synthe-
sized.[12–28] Recently, we prepared a five-coordinate model
complex
[Fe(2-CH2CO-6-MeOC5H3N)(CO)2{S-(2,6-
Me2C6H3)}] (1) with an open site.[25] However, 1 did not
react with H2 under ambient conditions. In continuation of
this work, similar mononuclear models with alkyl thiolate li-
gands were targeted. However, only dimeric complexes
Figure 2. Solid-state structure of 3a. The thermal ellipsoids are displayed
À
at a 50% probability. Selected bond lengths [ꢁ] and angles [8]: Fe1 N1
À
À
À
2.069(11), Fe1 C8 1.947(13), Fe1 C29 1.754(14), Fe1 C30 1.794(15),
À
À
[a] Dr. B. Hu, Prof. Dr. D. Chen
School of Chemical Engineering & Technology
Harbin Institute of Technology
Harbin 150001 (P.R. China)
Fe1 S1 2.367(4), Fe1 S2, 2.469(4); C29-Fe1-C30 90.4(6), C8-Fe1-N1,
82.9(5).
The 1H NMR spectrum of 3a in CD3CN exhibits three sig-
nals at 7.83, 7.06, and 6.82 ppm for the pyridyl rings, two sig-
nals at 7.79 and 7.29 ppm for the phenyl rings, and one dou-
blet at 4.52 and one multiplet at 3.88 ppm for the diastereo-
topic methylene hydrogen atoms and the methoxy groups.[29]
In the previously reported dinuclear complex [{Fe(6-MeO-
C5H3N-2-CH2CO)(CO)2(SCH2CH2OH)}2] (4),[27] four mul-
tiplets were found for -CH2CH2OH groups because the
E-mail: dafachen@hit.edu.cn
[b] Prof. Dr. X. Hu
Laboratory of Inorganic Synthesis and Catalysis
Institute of Chemical Sciences and Engineering
Ecole Polytechnique Fꢀdꢀrale de Lausanne (EPFL)
SB-ISIC-LSCI, BCH 3305, Lausanne 1015 (Switzerland)
E-mail: xile.hu@epfl.ch
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201300495.
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which was the product of the
reaction of 3a’ with CO
(Scheme 2).[29] This kind of car-
bonylation was demonstrated
by Rauchfuss et al. before.[16]
Reaction of
C6H4)SNa
2
and
with (2-F-
(2,4-F2-
C6H3)SNa gave [{Fe(2-CH2CO-
6-MeOC5H3N)(CO)2{S-(2-F-
ACHTUNGTRENNUNG
C6H4)}}2] (3b) and [{Fe(2-
CH2CO-6-MeOC5H3N)(CO)2{S-
(2,4-F2-C6H3)}}2] (3c), respec-
tively (Scheme 1). Like 3a,
Scheme 1. Reactions of 2 with sodium aryl thiolate.
bulky ligand environment around the Fe centers restricts the
rotation of the S-CH2 bonds. In principle, the Fe centers in
3a should be more sterically shielded than in 4, so it was
surprising that only two instead of four signals for the
phenyl rings were observed in the solution NMR spectrum.
This abnormality prompted us to record the IR spectrum of
3a in solution as well. Interestingly, only two intense n(CO)
absorption bands were observed in CH3CN and CHCl3
(Table 1). The reaction of 3a with CH3CN was further moni-
Scheme 2. Reaction of 3a’ with CO.
these compounds are dimeric in the solid state. The struc-
ture of 3b was also confirmed by X-ray crystallography.[29]
Both 3b and 3c convert to monomers (3b’ and 3c’) in solu-
tion (Scheme 1), which was confirmed by IR spectroscopy
(Table 1). The half-lives of 3b’ and 3c’ were both about 2 h
in the dark.
Table 1. Selected infrared data.
Complex
n˜CO [cmÀ1
]
3a[a]
2024, 2007, 1977, 1962
2032, 1973
2038, 1977
2031, 2011, 1980, 1965
2036, 1975
2028, 2004, 1986, 1961
2030, 1967
3a’[b]
3a’[c]
3b[a]
3b’[c]
Reaction of 2 with (2-CF3-C6H4)SNa gave a mixture of
[Fe(2-CH2CO-6-MeOC5H3N)(CO)2{S-(2-CF3-C6H4)}] (3d’)
3c[a]
3c’[b]
and
[Fe(2-CH2CO-6-MeOC5H3N)(CO)3{S-(2-CF3-C6H4)}]
3d’[a]
2025, 1962
2030, 1967
3d’[b]
(5d) (Scheme 3). At À308C, two species could be observed
3e[a]
2025, 1994, 1955, 1934
2015, 1951
2083, 2034, 2008
2085, 2035, 2008
2011, 1944
3e’[b]
5a[b]
5d[b]
[Fe]-hydrogenase[d]
FeGP cofactor[d]
2031, 1972
CO-inhibited cofactor[e] 2080 (the other two bands were not identified)
[a] Spectrum of a solid sample on KBr disk. [b] Spectrum of a sample dis-
solved in CH3CN. [c] Spectrum of a sample dissolved in CHCl3. [d] Spec-
trum of a sample dissolved in water; data from reference [30]. [e] Spec-
trum of a sample dissolved in water; data from reference [31].
Scheme 3. Reaction of 2 with (2-CF3-C6H4)SNa.
1
tored in CDCl3 by H NMR spectroscopy, and no reactivity
was found, confirming that CH3CN was not coordinated
with Fe. These observations indicate that a five-coordinate
monomer (3a’) rather than the dimeric 3a is the main spe-
cies in solution (Scheme 1). It is worth noting that the
n(CO) absorptions in CH3CN of 3a’ are almost identical to
that of the FeGP cofactor (Table 1).
with a ratio of 5:4 in the NMR spectrum of the product mix-
ture.[29] At room temperature, the signals from the two spe-
cies coalesced.[29] Thus, 3d’ and 5d were involved in a fast
self-exchange reaction, concomitant with the transfer of a
CO ligand. Unfortunately, pure 3d’ could not be isolated
from the mixture. When CO (1 atm) was added into this
mixture, 3d’ was converted into 5d.[29]
Complex 3a’ is unstable in solution at room temperature;
its half-life was about 1 h in the dark. One of the decompo-
sition products, interestingly, was the tris
[Fe(2-CH2CO-6-MeOC5H3N)(CO)3{S-(4-NO2-C6H4)}] (5a),
(carbonyl) complex
Analogous reactions of 2 with sodium aryl thiolates with-
out an electron-withdrawing group, for example, PhSNa, (2-
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Enzyme Models
COMMUNICATION
MeC6H4)SNa, (2-EtC6H4)SNa, (2-iPrC6H4)SNa, (2-OMe-
C6H4)SNa, and (4-MeC6H4)SNa, did not yield isolable com-
plexes, because of the instability of the expected products.
To obtain pure 3d’, an alternative route was attempted:
In summary, a series of new iron acyl thiolate complexes
have been synthesized and characterized. These complexes
can be used as structural and reactivity models for the
active site of [Fe]-hydrogenase. With electron-withdrawing
aryl thiolate ligands, five-coordinate mononuclear iron com-
plexes are the dominate species in solution. However, their
dimeric forms are more stable in the solid state. Substitution
at the ortho-position of the aryl thiolate is required to favor
the monomeric form in the solid-state. The first five-coordi-
nate iron acyl model complex with an alkyl thiolate ligand
(3e’) has also been prepared, albeit not isolated. The in-
sights gained from this study are useful for the development
of the next generation of model compounds.
[Fe(2-CH2CO-6-MeOC5H3N)(CO)2ACTHNUTRGNEUNG
(CH3CN)2]BF4 (6)[26] was
treated with (2-CF3-C6H4)SH in the presence of NEt3 at
À308C (Scheme 4). The reaction was fast, indicated by an
instantaneous change of color of the reaction medium from
yellow to red. The IR spectra of 3d, collected in the solid
state and in solution, both show two intense n(CO) absorp-
tion bands (Table 1). This result indicates that 3d’ exists in a
monomeric form even in the solid state. The half-life of 3d’
in solution was about 0.5 h.
Acknowledgements
This work is supported by the National Natural Science Foundation of
China (Nos. 21242012 and 21201049), the Fundamental Research Funds
for the Central Universities (Grant No. HIT. NSRIF. 2013042), and the
Swiss National Science Foundation (project no. 200020_134473/1).
Scheme 4. Reaction of 6 with (2-CF3-C6H4)SH and NEt3.
Keywords: alkyl · enzyme models · hydrogenase · iron ·
thiolate
A similar method was applied for the synthesis of
[{Fe(2-CH2CO-6-MeOC5H3N)(CO)2{S-
(tBu)}}2]
(3e)
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Chem. Eur. J. 2013, 00, 0 – 0
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Received: February 7, 2013
Published online: && &&, 0000
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Chem. Eur. J. 0000, 00, 0 – 0
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These are not the final page numbers!

Enzyme Models
COMMUNICATION
Enzyme models on the catwalk! A
series of new model complexes of the
active site of [Fe]-hydrogenase have
been synthesized and characterized.
These complexes are monomeric in
solution, but dimeric in the solid state.
Enzyme Models
B. Hu, D. Chen,* X. Hu* .. . &&&& — &&&&
Reversible Dimerization of Mononu-
clear Models of [Fe]-Hydrogenase
A unique bidentate pyridinol
cofactor…
… is to be found in [Fe]-hydroge-
nase. In their Communication on
page && ff., D. Chen, X. Hu and
B. Hu demonstrate the synthesis
and reactivities of a series of
mononuclear models, including the
first five-coordinate complex with
an alkyl thiolate ligand, that mimic
the main structure of [Fe]-hydroge-
nase active site. The equilibrium
between these models and their
dimeric components is also
described.
Chem. Eur. J. 2013, 00, 0 – 0
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www.chemeurj.org
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These are not the final page numbers!