Synthesis and reactivity of mononuclear iron models of [Fe]-hydrogenase that contain an acylmethylpyridinol ligand

Article abstract of DOI:10.1002/chem.201304290

[Fe]-hydrogenase has a single iron-containing active site that features an acylmethylpyridinol ligand. This unique ligand environment had yet to be reproduced in synthetic models; however the synthesis and reactivity of a new class of small molecule mimics of [Fe]-hydrogenase in which a mono-iron center is ligated by an acylmethylpyridinol ligand has now been achieved. Key to the preparation of these model compounds is the successful Ci￡O cleavage of an alkyl ether moiety to form the desired pyridinol ligand. Reaction of solvated complex [(2-CH₂CO-6-HOC₅H₃N)Fe(CO) ₂(CH₃CN)₂]⁺(BF₄) ^- with thiols or thiophenols in the presence of NEt₃ yielded 5-coordinate iron thiolate complexes. Further derivation produ Copyright

Full text of DOI:10.1002/chem.201304290

DOI: 10.1002/chem.201304290
Full Paper
&
Enzyme Models
Synthesis and Reactivity of Mononuclear Iron Models of [Fe]-
Hydrogenase that Contain an Acylmethylpyridinol Ligand
Bowen Hu,[a] Dafa Chen,*[a] and Xile Hu[b]
Abstract: [Fe]-hydrogenase has a single iron-containing
active site that features an acylmethylpyridinol ligand. This
unique ligand environment had yet to be reproduced in syn-
thetic models; however the synthesis and reactivity of a new
class of small molecule mimics of [Fe]-hydrogenase in which
a mono-iron center is ligated by an acylmethylpyridinol
ligand has now been achieved. Key to the preparation of
these model compounds is the successful CÀO cleavage of
an alkyl ether moiety to form the desired pyridinol ligand.
Reaction of solvated complex [(2-CH2CO-6-HOC5H3N)Fe(CO)2-
(CH3CN)2]+(BF4)À with thiols or thiophenols in the presence
of NEt3 yielded 5-coordinate iron thiolate complexes. Further
derivation
produced
complexes
and
[(2-CH2CO-6-
[(2-CH2CO-6-
HOC5H3N)Fe(CO)2(SCH2CH2OH)]
HOC5H3N)Fe(CO)2(CH3COO)], which can be regarded as
models of FeGP cofactors of [Fe]-hydrogenase extracted by
2-mercaptoethanol and acetic acid, respectively. When the
derivative complexes were treated with HBF4·Et2O, the sol-
vated complex was regenerated by protonation of the thio-
late ligands. The reactivity of several models with CO, isocya-
nide, cyanide, and H2 was also investigated.
Introduction
cofactor is mixed with the apoen-
zyme, an active [Fe]-hydrogenase
would be reconstituted. The struc-
tures of the protein-free cofactors
were proposed accordingly as in
Figure 2, and they were confirmed
Hydrogenases are enzymes that catalyze the production or
consumption of H2. Based on the metal atoms in the active
site, hydrogenases are classified in three types, namely [FeFe]-,
[NiFe]-, and [Fe]-hydrogenases.[1–5] Unlike the other two types
of hydrogenases, [Fe]-hydrogenase, which is also called H2-
forming methylene-tetrahydromethanopterin dehydrogenase
(Hmd), does not contain a redox-active site and a [Fe4S4] clus-
ter, and can only activate H2 in the presence of methenyltetra-
hydromethanopterin (methenyl-H4MPT+).[1,2]
In the active site of [Fe]-hydrogenase, a FeII center is coordi-
nated with two cis-CO, a cysteine sulfur atom (Cys 176), and
a bidentate acylmethylpyridinol ligand. The sixth position,
which is regarded as the H2-binding position, is probably occu-
pied by a labile water molecule (Figure 1).[6–8]
by mass spectrometry.[12,13]
Figure 1. The active site of
[Fe]-hydrogenase.
Since the elucidation of the
structure of [Fe]-hydrogenase,
a
number of model complexes
have been reported.[14–35] Recently we synthesized some five-
coordinate mononuclear iron complexes with a 2-acylmethyl-6-
methoxy-pyridyl ligand, which was a mimic to the acylmethyl-
pyridinol ligand in the enzyme. However, the hydroxy group of
the pyridinol ligand in the enzyme might carry a crucial func-
tion for H2 activation.[36,37] The faithful reproduction of such
secondary ligand environment in a model complex is therefore
a desirable goal in biomimetic chemistry. However, only a dinu-
clear iron complex with an acylmethylpyridinol ligand has
been reported; such a complex does not mimic the mononu-
The iron guanylylpyridinol (FeGP) cofactor of [Fe]-hydroge-
nase can be extracted by denaturation of the enzyme in the
presence of 2-mercaptoethanol or acetic acid.[9–13] If the FeGP
[a] Dr. B. Hu, Prof. Dr. D. Chen
School of Chemical Engineering and Technology
Harbin Institute of Technology
Harbin 150001 (China)
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)
ISIC-LSCI, BCH 3305
1015 Lausanne (Switzerland)
Fax: (+41)21-693-9305
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201304290.
Figure 2. The proposed structure of the FeGP cofactor extracted with 2-mer-
captoethanol (A) and extracted with acetic acid (B).
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clear nature of [Fe]-hydrogenase and is not suitable for further
reactivity study.[35] Herein, we report the synthesis and reactivi-
ty of the first mononuclear model complexes of [Fe]-hydroge-
nase that contain the previously elusive acylmethylpyridinol
ligand.
Results and Discussion
Iron complexes with a 2-acylmethyl-6-tert-butoxy-pyridyl
ligand
To install a pyridinol ligand, we first decided to incorporate
a pyridyl alkoxyl group from which the alkyl ether moiety
might be cleaved at a later stage. To this end, [(2-CH2CO-6-
tBuOC5H3N)Fe(CO)3I] (1) was prepared by dropwise addition of
lithiated 2-tert-butoxy-6-methylpyridine to [Fe(CO)5], followed
1
by treatment of I2 (Scheme 1). The H NMR spectrum of 1 in
Figure 3. Solid-state structure of 2.[41] Ellipsoids are set at 30% probability;
hydrogen atoms are omitted for clarity. Selected bond lengths [ꢁ] and
angles [o]: Fe1ÀN1 1.953(9), Fe1ÀS1 2.219(4), Fe1ÀC7 1.827(13), Fe1ÀC20
1.773(13), Fe1ÀC21 1.761(15), C20ÀO4 1.137(14), C21ÀO3 1.156(16), C7ÀO1
1.220(15); C21-Fe1-C20 90.8(6), C20-Fe1-N1 175.5(5), C7-Fe1-N1 86.3(5), C21-
Fe1-S1 163.5(4).
CH2CO-6-MeOC5H3N)Fe(CO)2{S-(2,6-Me2-C6H3)}].[28] The C21-Fe1-
S1 angle is 163.5(4)8, and the C20-Fe1-N1 angle is 175.5(5)8.
Thus, the coordination geometry of the Fe ion is best de-
scribed as distorted square-pyramidal. The bidentate acylme-
thylpyridyl ligand coordinates with Fe by the pyridyl nitrogen
and acyl carbon donors. The two CO and the acyl ligands are
all mutually cis. The sulfur ligand is cis to the acyl and pyridyl
ligands, and the position trans to the acyl ligand is unoccu-
pied. The IR spectrum of 2 shows two equally intense n(CO)
absorptions at 2013 and 1948 cmÀ1 in the solid state, which is
consistent with the existence of two cis-CO ligands (Table 1).
Scheme 1. Synthesis of complex 1.
CDCl3 exhibits three signals at d=7.73, 7.11, and 6.99 ppm for
the pyridyl rings, two doublets at d=5.42 and 4.29 ppm for
the diastereotopic methylene hydrogen atoms, and one singlet
at d=1.70 ppm for the tert-butoxy group.[38] The results indi-
cate a single isomer in the solution. The IR spectrum of
1 shows three n(CO) absorptions in CH2Cl2; in the solid state,
1 displays five absorptions,[38] which might be caused by inter-
actions between molecules in the solid lattice. Similar phenom-
enon has been found in complex [Fe(S2C2H4)(CO)2(PMe3)2].[39]
Reaction of 1 with NaS(2,6-Me2C6H3) gave a five-coordinate
complex [2-CH2CO-6-tBuOC5H3N)Fe(CO)2{S-(2,6-Me2-C6H3)}] (2)
(Scheme 2), which was characterized by X-ray crystallography
(Figure 3). The structure of 2 is similar to that of complex [2-
1
The H NMR spectrum of 2 in CD3CN exhibits four signals at
d=7.97, 7.24–7.20, 7.07, and 6.96 ppm for the pyridyl and
phenyl rings, two doublets at d=4.44 and 4.04 ppm for the
diastereotopic methylene hydrogen atoms, one singlet at d=
2.30 ppm for the methyl group, and one singlet at d=
1.58 ppm for the tert-butoxy group.[38] No reactivity with H2
1
was detected by monitoring with H NMR spectroscopy. How-
ever, CO could occupy the open position in complex 2, giving
a tricarbonyl complex [2-CH2CO-6-tBuOC5H3N)Fe(CO)3{S-(2,6-
Me2-C6H3)}] (3) (Scheme 2). Compound 3 was characterized by
1
1H NMR, 13C NMR, and IR spectroscopy. The H NMR spectrum
exhibits two doublets at d=5.18 and 4.05 ppm for the diaste-
reotopic methylene hydrogen atoms, and the 13C NMR spec-
trum shows one signal at d=260.9 ppm for the acyl carbon
and three signals at d=210.3, 208.3, and 205.8 ppm for termi-
nal carbonyl carbon atoms. The IR spectrum of 3 shows three
intense n(CO) absorption bands (Table 1). The third CO ligand
in 3 is labile. When a solution of 3 was purged with N2, com-
plex 2 was regenerated (Scheme 3).
Attempts to remove the tBu group in 2 with Me3SiI were un-
successful, and some unidentified species were formed. Com-
Scheme 2. Synthesis of complex 2.
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Iron complexes with an acylmethylpyridinol ligand
Table 1. Selected IR spectroscopy data.
Complex n(CO) [cmÀ1
]
Complex
n(CO) [cmÀ1
]
The difficulty in the deprotection of the tBu group in complex
2 might be due to the instability of the targeted complex, so
we next attempted to deprotect the tBu group in the more
stable complex 1. This proved successful. Reaction of 1 with an
excess of Me3SiI (3.5 equiv) followed by addition of H2O yielded
[(2-CH2CO-6-HOC5H3N)Fe(CO)3I] (5) (Scheme 5). In CH3CN, the IR
2[a]
2013, 1948
9a[b]
2074, 2020,
1989
2017, 1956
3[b]
2078, 2027,
2001
10[b]
4[a]
6[a]
6[b]
7[b]
7a[b]
2047, 1988
2057, 1999
2065, 2010
2011, 1944
2063, 2011,
1983
11[b]
2008, 1947
2006, 1937
2042, 1972
2051, 1986
1996, 1928
12[b]
13[a]
13 in CH2Cl2
Hmd[c]
8[a]
8[b]
2014, 1953
2013, 1953
Hmd[d]
CO-inhibited Hmd[d]
2011, 1944
2074, 2020,
1981
9[a]
9[b]
2024, 1960
2020, 1956
2022, 1958
Mercaptoethnol-FeGP cofac- 2004, 1934
tor[e]
Mercaptoethnol-FeGP cofac- 2031, 1972
tor[d]
Scheme 5. Synthesis of complex 5.
9 in
Acetic acid-FeGP cofactor[e]
2029, 1957
CH2Cl2
spectrum of 5 exhibits three n(CO) absorptions, which is con-
sistent with its structure.[38] In the solid state, its IR spectrum
shows four n(CO) absorptions, which is probably due to the
same reason proposed for complex 1 (see above).
[a] Spectrum of a solid sample on KBr disk. [b] Spectrum of a sample dis-
solved in CH3CN. [c] Spectrum of a solid sample; data from Ref. [7].
[d] Spectrum of a sample dissolved in water; data from Ref. [40]. [e] Spec-
trum of a solid sample; data from Ref. [13].
1
The H NMR spectrum of 5 in CD3CN exhibits one singlet at
d=10.17 ppm for the hydroxy group, three signals at d=7.81,
7.08, and 6.87 ppm for the pyridyl ring, and two doublets at
d=4.46 and 4.08 ppm for the CH2 group. No tBu group is
shown, which is in agreement with the cleavage of the tBu
group.[38]
After the synthesis of 5, we set out to install a thiolate
ligand on the Fe center. Reactions of 5 with PhSNa, 2,6-
Me2C6H3SNa, 4-NO2-C6H4SNa, and C6F5SNa did not yield isolable
complexes.
An alternative route was developed to synthesize the de-
sired iron thiolate model complexes. Complex 5 was treated
with AgBF4 in CH3CN, giving [(2-CH2CO-6-HOC5H3N)Fe(CO)2-
(CH3CN)2]+(BF4)À (6) (Scheme 6). The two intense n(CO) absorp-
Scheme 3. Reversible reaction of 2 with CO.
pound 2 was also treated with CF3COOH/CH3CN, but only an
ionic
product
[(2-CH2CO-6-tBuOC5H3N)Fe(CO)2(CH3CN)2]+
(CF3COO)À (4) was generated in a quantitative yield in CH3CN
(Scheme 4). Complex 4 is not stable in other solvents such as
CH2Cl2 and THF. The IR spectrum of 4 in the solid state shows
two intense n(CO) absorption bands at 2047 and 1988 cmÀ1
(Table 1), which are comparable with the known ionic complex
[(2-CH2CO-6-MeOC5H3N)Fe(CO)2(CH3CN)2]+(BF4)À,[30] and much
higher than that of 2 and [Fe]-hydrogenase. The structure of 4
Scheme 6. Synthesis of complex 6.
1
was further confirmed by a H NMR spectrum and elemental
analysis.
tion bands in its IR spectra (2057 and 1999 cmÀ1 in the solid
state; 2065 and 2010 cmÀ1 in CH3CN) are comparable to that
of 4, and confirm its ionic nature (Table 1). Compound 6 was
treated with a series of thiols and thiophenols in the presence
of NEt3 at À308C to give the targeted thiolate complexes
(Scheme 7).
Complexes [(2-CH2CO-6-HOC5H3N)Fe(CO)2{S-(2,6-Me2-C6H3)}]
(7) and [(2-CH2CO-6-HOC5H3N)Fe(CO)2{S-(4-NO2-C6H4)}] (8) are
highly unstable, and they decomposed completely in 10 min in
the dark at À308C. The instability made it impossible to obtain
Scheme 4. Reaction of 2 with CF3COOH.
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converted into the tris(carbonyl) complexes.[40] It is worth
noting that both the n(CO) absorption bands of 7a and 9a are
close to those of CO-inhibited [Fe]-hydrogenase (Table 1).
One of the decomposition products of 7 was identified as
the tricarbonyl complex 7a (Supporting Information, Fig-
ure S12).[38] This decomposition pathway was earlier found for
complex
[(2-CH2CO-6-MeOC5H3N)Fe(CO)2{S-(4-NO2-C6H4)}]2.[33]
After 2 min at À308C, two new peaks at 2063 and 1983 cmÀ1
appeared, which were attributed to 7a. After about 10 min,
the decomposition of 7 was complete.[38]
Scheme 7. Synthesis of thiolate iron complexes.
The decomposition reaction of 9 was similar to that of 7,
and 9a was also formed (Supporting Information, Fig-
ure S19).[38]
1
satisfying H NMR spectra of these complexes. Their IR spectra
To model the isocyanide- and cyanide-inhibited [Fe]-hydro-
genase,[37,40] the reactions of 9 with p-toluenesulfonylmethyli-
socyanide and [NEt4]CN were explored. Treatment of 9 with p-
toluenesulfonylmethylisocyanide gave an unstable dicarbonyl
product.[38] Treatment of 9 with [NEt4]CN gave unidentified
products. Installation of a 2-mercaptoethanol ligand onto the
Fe center was also attempted to model the protein-free FeGP
cofactor extracted with 2-mercaptoethanol. When 6 was treat-
ed with 2-mercaptoethanol in the presence of NEt3, [(2-CH2CO-
in CH3CN and in the solid state show two intense n(CO) ab-
sorption bands, indicating their existence as monomers both
in solution and in the solid state (Table 1).
The complex [(2-CH2CO-6-HOC5H3N)Fe(CO)2{S-(C6F5)}] (9) is
much more stable. It has a lifetime of about 1 h at room tem-
perature in the dark. Ambient light accelerates its decomposi-
tion (lifetime of about 30 min). From the reaction of 6 with
C6F5SNa, the 1H NMR spectrum of 9 could be obtained, al-
though the resolution was not high owing to the existence of
some paramagnetic impurities. The two characteristic doublets
of the diastereotopic methylene hydrogen atoms at d=4.66
and 3.91 ppm were evident. The reaction of 9 with H2 (1 atom-
6-HOC5H3N)Fe(CO)2(SCH2CH2OH)]
(12)
was
produced
(Scheme 9). The IR spectrum of 12 shows two absorptions at
1
sphere) was monitored by H NMR spectroscopy; however, no
reaction was found. The result is consistent with the essential
role of methenyl-H4MPT+ for H2 activation by [Fe]-hydroge-
nase. It also suggests that replacing the methoxyl group in 2
and its analogues by a hydroxy group as in 9 does not result
in a dramatic change in the reactivity towards H2.
Like 7 and 8, complexes [(2-CH2CO-6-HOC5H3N)Fe(CO)2(S-
tBu)] (10) and [(2-CH2CO-6-HOC5H3N)Fe(CO)2(SCH2CH2CH3)] (11)
could only be identified by IR spectroscopy owing to their
high instability. From the two intense absorptions (2017 and
1956 cmÀ1 for 10; 2008 and 1947 cmÀ1 for 11) (Table 1), both
10 and 11 exist as monomers in CH3CN. The lifetime of 10 and
11 is only about 3 min at À308C.
Scheme 9. Synthesis of complex 12.
2006 and 1937 cmÀ1 in CH3CN, within several cmÀ1 of those of
2-mercaptoethanol extracted FeGP cofactor in the solid state
(Table 1). In contrast to the five-coordinate models 7 and 9,
compound 12 did not react with CO, which is similar to the
FeGP cofactor extracted with 2-mercaptoethanol.[40] This sug-
gests that 12 is a six-coordinate complex, with OH group of 2-
mercaptoethanol coordinating to Fe.
Compounds 7 and 9 were further selected to study the reac-
tivity with CO. Unexpectedly, upon exposure to CO, the con-
version
into
tricarbonyl
products
[(2-CH2CO-6-
HOC5H3N)Fe(CO)3{S-(2,6-Me2-C6H3)}] (7a) and [(2-CH2CO-6-
HOC5H3N)Fe(CO)3{S-(C6F5)}] (9a) was not complete (33% for 7
and 38% for 9) (Scheme 8).[38] This behavior is different from
that of 2 and [Fe]-hydrogenase, which could be completely
Unlike
the
dinuclear
complexes
[(2-CH2CO-6-
[(2-CH2CO-6-
[33]
MeOC5H3N)Fe(CO)2{S-(4-NO2-C6H4)}]2
and
MeOC5H3N)Fe(CO)2{SCH2CH2OH)}]2,[31] 7–12 all exist as mono-
mers (Table 1). The results demonstrate that the 6-hydroxy
group in the pyridyl ring has certain influences over their struc-
tures and possibly activities.
To model the acetic acid extracted FeGP cofactor, acetate
ligand was also installed by reacting 5 with CH3COOAg in
CH2Cl2 (Scheme 10).
1
The H NMR spectrum of the product in CDCl3 exhibits three
signals at d=7.67, 6.86, and 6.68 ppm for the pyridinol ring,
two doublets at d=4.01 and 3.92 ppm for the ÀCH2 group,
and one singlet at d=2.41 ppm for the acetate group. The IR
spectrum displays two intense n(CO) absorptions both in the
Scheme 8. Reversible reactions of 7 and 9 with CO.
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An acetate ligand was installed
in complex 13, which serves as
a model of the acetic acid ex-
tracted FeGP cofactor. The lack
of reactivity of these new
models towards H2 echoes that
of [Fe]-hydrogenase, and sug-
gests that methenyl-H4MPT+
and the enzymatic environment
are essential for H2 activation.
Scheme 10. Reaction of 5 with CH3COOAg.
solid state and in CH2Cl2 (Table 1).[38] The ESI-MS (negative
mode) shows an intense peak at 305.9706. All the data are
consistent with the formulation of the product as [(2-CH2CO-6-
HOC5H3N)Fe(CO)2(CH3COO)] (13) (calculated mass: 305.9701).
Interestingly, two species with a ratio of about 2:1 were de-
tected when 13 was dissolved in CH3CN, according to the four
characteristic peaks in the 1H NMR spectrum at d=4.20, 4.05,
3.85, and 3.82 ppm for the CH2 groups in CD3CN. The IR spec-
Experimental Section
Synthesis of [(2-CH2CO-6-HOC5H3N)Fe(CO)3I] (5)
Me3SiI (610.0 mg, 3.05 mmol) was added into
a solution of
1 (400.0 mg, 0.871 mmol) in CH2Cl2 (10 mL) under stirring at room
temperature. After 12 h, H2O (20 mL) was added into the mixture.
The water phase was washed with CH2Cl2 (3ꢂ20 mL) and ether
(10 mL), respectively. The combined organic phase was washed
with H2O (20 mL). After drying the organic phase over Na2SO4 and
evaporation of the solvent, the residue was extracted with ether
(10 mL), and the filtrate was dried in vacuum. The residue was
washed with hexane (40 mL) and CH2Cl2 (1 mL), respectively. The
solid residue was then extracted with ether (10 mL) again, and the
filtrate was dried in vacuum. The residue was washed with hexane
(20 mL) and recrystallized from ether/hexane to afford 5 (110.0 mg,
0.273 mmol; yield: 31%) as a red solid.
1
trum is also consistent with the H NMR result, and shows four
n(CO) absorption bands.[38] We propose that a second species
formed when 13 is dissolved in CH3CN, and this species is [(2-
CH2CO-6-HOC5H3N)Fe(CO)2(CH3CN)2]+(CH3COO)À
(Scheme 10).
(13a)
Complex 13 could react with C6F5SH/NEt3 to generate 9.
When CH2Cl2 was used as the solvent for this reaction, two in-
tense n(CO) absorptions at 2022 and 1958 cmÀ1 were observed
in the IR spectrum of the product, nearly identical to those of
9 produced according to Scheme 7 (Table 1).[38] The reaction of
9 produced from 13 with CH3CN (20 equiv) was monitored in
CH2Cl2, but no reaction was found. This result indicates that 9
is five-coordinate and CH3CN does not coordinate to Fe, as
proposed in Scheme 7.
1H NMR (400.13 MHz, CD3CN): 10.17 (s, 1H), 7.81 (t, J=8.0 Hz, 1H),
7.08 (d, J=8.0 Hz, 1H), 6.87 (d, J=8.0 Hz, 1H), 4.46 (d, J=20.0 Hz,
1H), 4.08 ppm (d, J=20.0 Hz, 1H); IR (nCO, KBr):n˜ =2102 (s), 2048
(s), 2023 (s), 2014 cmÀ1 (s); IR (nCO, CH CN): n=2068 (s), 2050 (s),
˜
3
1996 cmÀ1 (s); elemental analysis calcd (%) for C10H6FeNO5I: C 29.8,
H 1.5, N 3.5; found: C 30.1, H 1.5, N 3.8.
Synthesis of [(2-CH2CO-6-HOC5H3N)Fe(CO)2(CH3CN)2]+(BF4)À
(6)
Similar
to
[2-CH2CO-6-MeOC5H3N)Fe(CO)2{S-(2,6-Me2-
C6H3)}],[30] complexes 7–12 reacted with HBF4·Et2O/CH3CN to
form 6. This reactivity again suggests that the Cys176 thiolate
ligand in [Fe]-hydrogenase might serve as a proton acceptor
after H2 splitting.[30]
AgBF4 (48.1 mg, 0.248 mmol) was added into a solution of 5
(100.0 mg, 0.248 mmol) in CH3CN (5 mL) under stirring. Gas (CO)
was formed immediately. After 1 min, the mixture was filtered and
the filtrate was dried in vacuum. The residue was washed with
ether (10 mL) and dried in vacuum to afford
0.242 mmol; 98%) as a light yellow oily solid.
6 (101.0 mg,
1H NMR (400.13 MHz, CD3CN): 9.33 (s, 1H), 7.83 (t, J=8.0 Hz, 1H),
7.10 (d, J=8.0 Hz, 1H), 6.88 (d, J=8.0 Hz, 1H), 4.66 (d, J=20.0 Hz,
1H), 3.89 (d, J=20.0 Hz, 1H), 1.96 ppm (s, 6H); IR (nCO, KBr): n˜ =
2057 (s), 1999 cmÀ1 (s); IR (nCO, CH3CN): n˜ =2065 (s), 2010 cmÀ1 (s);
elemental analysis calcd (%) for C13H12BF4FeN3O4: C 37.5, H 2.9,
N 10.1; found: C 37.7, H 3.0, N 9.9.
Conclusion
In summary, two mononuclear iron complexes with acylme-
thylpyridinol ligand (5 and 6) were synthesized and fully char-
1
acterized by H NMR and IR spectroscopy and elemental analy-
sis. Starting from 6, a series of iron thiolate complexes (7–12)
were generated and identified by IR and/or H NMR (9) spec-
1
troscopy. These complexes are the first mononuclear iron
models of [Fe]-hydrogenase that contain an acylmethylpyridi-
nol ligand. In contrast to the known complexes with a 2-acyl-
methyl-6-methoxy-pyridyl ligand,[31,33] 7–12 always exist as
monomers and are not subject to dimerization. This is evi-
dence that the 6-hydroxy group in the pyridyl ring can influ-
ence the structures and probably the activity of the model
complexes. Compounds 7–12 reacted with HBF4 to generate 6,
which is consistent with the Cys176 thiolate ligand in [Fe]-hy-
drogenase being a possible proton acceptor after H2 splitting.
General procedure of the synthesis of thiolate complexes 7–
12
Thiol or thiophenol (0.048–0.096 mmol, 1–2 equiv) was added into
a solution of 6 (20.0 mg, 0.048 mmol) in CH3CN (5 mL) under stir-
ring. NEt3 (0.048–0.096 mmol, 1–2 equiv) was added into the mix-
ture at À308C. The IR spectrum was recorded immediately. If
HBF4·Et2O (0.048–0.14 mmol, 1–3 equiv) was added quickly after
the formation of the thiolate product, 6 was regenerated.
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Keywords: carbonyl complexes
hydrogenases · iron · thiolates
·
enzyme models
·
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Published online on January 8, 2014
Chem. Eur. J. 2014, 20, 1677 – 1682
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1682
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim