A novel acylmethylpyridinol ligand containing dinuclear iron complex closely related to [Fe]-hydrogenase

Article abstract of DOI:10.1021/om400240e

On synthesizing the PMB-protected mononuclear iron complexes [2-C(O)CH ₂-6-PMBOC₅H₃N]Fe(CO)₃I (6) and [2-C(O)CH₂-6-PMBOC₅H₃N]Fe(CO) ₂(2-SC₅H₄N) (7), the novel acylmethylpyridinol ligand containing dinuclear iron complex [2-C(O)CH₂-6-HOC ₅H₃N]Fe₂(CO)₄[2′-C(O)CH ₂-6′-OC₅H₃N](2-SC₅H ₄N) (9), which is closely related to the active site of [Fe]-hydrogenase, has been prepared unexpectedly via removal of the PMB protecting group from 7 under the action of excess trifluoroacetic acid. The [Fe]-hydrogenase-related complex 9 and its precursor complexes 6 and 7 have been fully characterized by elemental analysis, spectroscopy, and X-ray crystallography.

Full text of DOI:10.1021/om400240e

Communication
pubs.acs.org/Organometallics
A Novel Acylmethylpyridinol Ligand Containing Dinuclear Iron
Complex Closely Related to [Fe]-Hydrogenase
Li-Cheng Song,* Gao-Yu Zhao, Zhao-Jun Xie, and Ji-Wei Zhang
Department of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, People’s
Republic of China
S
* Supporting Information
ABSTRACT: On synthesizing the PMB-protected mononuclear iron complexes [2-
C(O)CH2-6-PMBOC5H3N]Fe(CO)3I (6) and [2-C(O)CH2-6-PMBOC5H3N]Fe-
(CO)2(2-SC5H4N) (7), the novel acylmethylpyridinol ligand containing dinuclear iron
complex [2-C(O)CH2-6-HOC5H3N]Fe2(CO)4[2′-C(O)CH2-6′-OC5H3N](2-SC5H4N)
(9), which is closely related to the active site of [Fe]-hydrogenase, has been prepared
unexpectedly via removal of the PMB protecting group from 7 under the action of excess
trifluoroacetic acid. The [Fe]-hydrogenase-related complex 9 and its precursor complexes
6 and 7 have been fully characterized by elemental analysis, spectroscopy, and X-ray
crystallography.
Scheme 2. Active Site of [Fe]-Hydrogenase
n nature, there are three kinds of hydrogenases, namely
I[FeFe]-, [NiFe]-, and [Fe]-hydrogenases. Although the
three enzymes are phylogenetically unrelated, they all can
catalyze H2 metabolism in various microorganisms.1−4
However, unlike the [FeFe]- and [NiFe]-hydrogenases,4
[Fe]-hydrogenase (Hmd)1,2 is not redox-active and catalyzes
the reversible reduction of methenyltetrahydromethanopterin
(methenyl-H4MPT+) with H2 to methylenetetrahydrometha-
nopterin (methylene-H4MPT) and H+ (Scheme 1). This
catalytic process is an intermediary step in the reduction of
CO2 to methane using H2 by methanogens grown under nickel-
deficient conditions.5
previously reported. It is worth noting that an [Fe]-hydro-
genase model complex with a natural 2-acylmethyl-6-pyridinol
ligand is of particular interest, since the hydroxy group that is
directly attached to the pyridine ring of the natural ligand in
[Fe]-hydrogenase plays an important role in the heterolytic
cleavage of dihydrogen.25 Therefore, in order to further
understand the active site structure of [Fe]-hydrogenase and
its catalytic mechanism, we initiated a study aimed at
synthesizing the 2-acylmethyl-6-pyridinol ligand containing
[Fe]-hydrogenase model complex. As a result, in contrast to
our original expectation, we did not get such a mononuclear
iron model complex; instead, we obtained a novel dinuclear
iron complex in which the acylmethylpyridinol ligand is
coordinated to one of its two iron atoms and a deprotonated
acylmethylpyridinol ligand is coordinated to both of its iron
atoms. In this communication, we report the synthesis and
structural characterization of this novel dinuclear complex,
which is closely related to the active site of [Fe]-hydrogenase.
The synthetic route for preparation of such a dinuclear
complex, namely 9, is shown in Schemes 3 and 4. First, as
shown in Scheme 3, the methoxycarbonyl-substituted pyridinol
2-MeO2C-6-HOC5H3N (1) reacted with 4-MeOC6H4CH2Cl in
MeCN in the presence of K2CO3/NaI to give the p-
Scheme 1. Catalytic Function of [Fe]-Hydrogenase
Recent X-ray crystallographic6−8 and spectroscopic9−12
studies have demonstrated that the active site of [Fe]-
hydrogenase contains a unique iron atom ligated by a cysteine
S atom, two cis carbonyls, a 2-acylmethyl-6-pyridinol, and an as
yet unknown ligand, which is presumably a molecule of water
(Scheme 2).
So far, a number of biomimetic models for [Fe]-hydrogenase
have been synthesized, but none of them contain the natural 2-
acylmethyl-6-pyridinol ligand,13−24 although some model
complexes with a similar ligand of acylmethyl(methoxy)-
pyridine20−22 or acylmethyl(hydroxymethyl)pyridine24 were
Received: March 21, 2013
Published: April 30, 2013
© 2013 American Chemical Society
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complex 8 was not obtained; instead, the novel dinuclear iron
complex [2-C(O)CH2-6-HOC5H3N]Fe2(CO)4[2′-C(O)CH2-
6′-OC5H3N](2-SC5H4N) (9), which contains the natural
acylmethylpyridinol ligand, was obtained in 36% yield,
unexpectedly. It should be noted that according to the proton
acid catalyzed ether cleavage mechanism27 and the Lewis acid
catalyzed PMB-removed mechanism,28 complex 7 might be first
converted to the initially expected 8, and then 9 was generated
via the in situ self-assembly of 8 in the presence of excess
CF3CO2H (the suggested pathway for formation of the
unexpected 9 is shown in Scheme S1 of the Supporting
Information).
Scheme 3. Synthesis of the PMB-Protected Pyridinol
Derivatives 2−4
These three complexes were fully characterized by elemental
analysis, spectroscopy, and X-ray crystallography. The solid-
state IR spectrum of 6 showed three absorption bands in the
range 2085−2005 cm−1 for its three terminal CO ligands,
whereas 7 and 9 displayed two absorption bands in the regions
2022−1958 and 2031−1977 cm−1 for their two and four
terminal CO ligands, respectively. The IR spectra of 6, 7, and 9
also displayed one strong absorption band in the range 1672−
1653 cm−1 for their acyl groups, which are very close to those
of the previously reported acylmethylpyridinyl ligand contain-
ing model complexes.20,24
Scheme 4. Synthesis of the Mono- and Dinuclear Complexes
6, 7, and 9
The 1H NMR spectra of 6, 7, and 9 showed two doublets in
the range 3.75−5.12 ppm for the two diastereotopic H atoms in
their acylmethyl groups, whereas their 13C NMR spectra
displayed one or two singlets in the region 258−265 ppm for
their acyl C atoms. These NMR data are also very close to
those of the previously reported acylmethylpyridinyl ligand
containing model complexes.20,24 It is particularly noteworthy
1
that the IR and H NMR spectra of 9 all showed the presence
of the hydroxy group of the acylmethylpyridinol ligand by
having a weak band at 3469 cm−1 and a singlet at 13.58 ppm,
respectively (see the Supporting Information).
The molecular structures of 6, 7, and 9 have been
unambiguously confirmed by X-ray crystal diffraction analysis.
As can be seen in Figures 1 and 2, the Fe1 centers of 6 and 7
are six-coordinate and their acylmethyl/PMBO-disubstituted
pyridine ligands each construct a five-membered ferracycle with
their Fe1 centers, respectively. The three terminal CO ligands
methoxybenzyl (PMB)-protected pyridinol derivative 2-
MeO2C-6-PMBOC5H3N (2). Then, the methoxycarbonyl
group of 2 was reduced to a hydroxymethyl group by NaBH4
in THF/MeOH to produce 2-HOCH2-6-PMBOC5H3N (3).
Furthermore, 3 reacted in THF with 4-toluenesulfonyl (Ts)
chloride in the presence of KOH to afford the corresponding
disubstituted pyridine derivative 2-TsOCH2-6-PMBOC5H3N
(4) in a nearly quantitative yield. All three new PMB-protected
pyridinol derivatives 2−4 were fully characterized by elemental
analysis and IR and NMR spectroscopic methods (see the
Supporting Information).
Then as shown in Scheme 4, when the PMBO/TsOCH2-
disubstituted pyridine 4 reacted with Na2Fe(CO)4·1.5(1,4-
dioxane) in MeCN, similar to the case for its HOCH2/
TsOCH2-disubstituted analogue,24 the intermediate iron(0)
complex salt Na(2-CH2-6-PMBOC5H3N)Fe(CO)4 (5) was
first formed and the in situ CO migratory insertion/oxidation
reaction of 5 in the presence of iodine26 afforded the PMB-
protected acylmethylpyridinol ligand containing iron(II) iodide
complex [2-C(O)CH2-6-PMBOC5H3N]Fe(CO)3I (6). Further
treatment of 6 with potassium 2-mercaptopyridinate, via
displacement of iodide by 2-mercaptopyridinate and subse-
quent coordination of the pyridyl N atom and loss of one CO
ligand, yielded the corresponding iron(II) mercaptopyridinate
complex [2-C(O)CH2-6-PMBOC5H3N]Fe(CO)2(2-SC5H4N)
(7). It is particularly worth pointing out that when we
attempted to use CF3CO2H to remove the protecting group
PMB from 7, the initially expected mononuclear model
Figure 1. Molecular structure of 6 with 50% probability level
ellipsoids. Key bond lengths (Å) and angles (deg): Fe(1)−C(1) =
1.893(5), Fe(1)−C(4) = 1.989(4), Fe(1)−N(1) = 2.035(3), Fe(1)−
I(1) = 2.6582(11), O(4)−C(4) = 1.198(4); C(1)−Fe(1)−C(4) =
175.50(16), C(3)−Fe(1)−N(1) = 167.90(17), C(2)−Fe(1)−C(1) =
94.43(19), C(1)−Fe(1)−I(1) = 87.25(13).
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by the 2-mercaptopyridinate S1 atom, two cis carbonyls, and
the deprotonated pyridinol O4 atom, whereas the Fe2 center of
9 is coordinated by the corresponding ligand atoms such as S1,
C21/C20, and N1. It follows that (i) the Fe1 center of complex
9 has a complete set of coordinated atoms of the active site of
[Fe]-hydrogenase and (ii) the Fe1 and Fe2 centers both have a
formal oxidation state of +2 achieved by coordination of the
corresponding negative ligands around the Fe1 and Fe2
centers. Although early studies indicate the Fe center in [Fe]-
hydrogenase to be either low-spin Fe(0) or low-spin Fe(II),11
recent studies show that the Fe center of [Fe]-hydrogenase is
most likely low-spin Fe(II).14,31 Therefore, the formal oxidation
state assigned to the Fe1 and Fe2 centers of the dinuclear
complex 9, as well as that assigned to the Fe1 centers of
mononuclear complexes 6 and 7 as mentioned above, are all
consistent with that recent assignment of Fe(II) for the Fe
center of [Fe]-hydrogenase.14,31 Finally, it should be noted that
in molecular structure of 9 there exists an intramolecular
hydrogen bond between the hydroxy H2 atom of the
acylmethylpyridinol ligand and the O4 atom of the
deprotonated pyridinol ligand (O2−H2- - -O4 = 2.483 Å,
∠O2−H2- - -O4 = 173.71°). Such a type of hydrogen bond
might be helpful in understanding the natural hydrogen
bonding present in [Fe]-hydrogenase.5,8
In summary, we have prepared the novel dinuclear iron
complex 9 via a multistep synthetic route involving starting
compound 1, PMB-protected derivatives 2−4, and PMB-
protected complexes 6 and 7. It is particularly noteworthy that
the final step of the multistep synthetic route includes the
unexpected reaction of 7 with CF3CO2H to give 9. The most
striking feature of 9 is that it has one Fe(II) center with a
natural 2-acylmethyl-6-pyridinol ligand and a complete set of
coordinated atoms of the active site of [Fe]-hydrogenase.
Another feature of 9 is to have a deprotonated pyridinol ligand
coordinated to both of its Fe(II) centers. The third feature of 9
is to have an intramolecular hydrogen bond between the
pyridyl hydroxy group and the deprotonated pyridinol O atom.
It follows that the preparation and structural characterization of
9 makes it possible to further study the chemical reactivities of
the pyridyl hydroxy group so as to further understand the
catalytic mechanism assisted by such a hydroxy group in [Fe]-
hydrogenase.
Figure 2. Molecular structure of 7 with 30% probability level
ellipsoids. Key bond lengths (Å) and angles (deg): Fe(1)−C(8) =
1.923(3), Fe(1)−N(2) = 2.057(3), Fe(1)−N(1) = 2.060(2), Fe(1)−
S(1) = 2.3765(11), O(3)−C(8) = 1.211(4), O(4)−C(14) = 1.348(4);
C(2)−Fe(1)−N(2) = 172.13(12), C(1)−Fe(1)−S(1) = 175.56(10),
C(1)−Fe(1)−N(2) = 90.19(12), C(2)−Fe(1)−C(1) = 91.67(16).
in 6 occupy the facial positions of the Fe1 octahedral geometry,
whereas the two terminal CO ligands of 7 lie in positions cis to
its acyl ligand. In addition, in 7 there is also a bidentade
mercaptopyridinate ligand chelated to its Fe1 center.
It can be seen in Figure 3 that complex 9 is indeed a
dinuclear complex, in which the Fe1 center is coordinated by a
ASSOCIATED CONTENT
■
S
* Supporting Information
Figure 3. Molecular structure of 9 with 30% probability level
ellipsoids. Key bond lengths (Å) and angles (deg): O(2)−C(7) =
1.323(3), O(4)−C(14) = 1.306(2), Fe(1)−C(12) =1.927(2), Fe(1)−
N(2) = 2.0484(17), Fe(1)−O(4) = 2.0861(14), Fe(1)−S(1) =
2.3301(6), Fe(2)−C(19) = 1.933(2), Fe(2)−N(3) = 2.0188(17),
Fe(2)−N(1) = 2.0221(17), Fe(2)−S(1) = 2.4837(6); C(23)−Fe(1)−
C(22) = 89.30(9), C(22)−Fe(1)−S(1) = 176.90(7), C(21)−Fe(2)−
N(1) = 178.20(8), C(19)−Fe(2)−S(1) = 159.73(6), C(21)−Fe(2)−
C(20) = 91.40(9).
Text and a scheme giving full experimental details for 2−4, 6, 7,
and 9 and a table and CIF files giving crystallographic data for
6, 7, and 9. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail for L.-C.S.: lcsong@nankai.edu.cn.
2-acylmethyl-6-pyridinol ligand (C7−O2 = 1.323 Å) via its acyl
C12 and pyridyl N2 atoms and the Fe2 center is coordinated by
a deprotonated 2-acylmethyl-6-pyridinol ligand via its acyl C19
and pyridyl N3 atoms (this deprotonated pyridinol ligand
might be also regarded as a deprotonated pyridone ligand, since
the bond lengths of C14−O4 (1.306 Å) and C14−N3 (1.365
Å) are between those of the corresponding single and double
bonds).29,30 In addition, the Fe1 center of 9 is also coordinated
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the NSF (grant numbers 21132001 and
21272122) and 973 (grant number 2011CB935902) of China
for financial support of this work.
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