Cationic and anionic dinuclear nickel complexes [Ni(N2S 2)Ni(dtc)]n (n=-1, +1) modeling the active site of acetyl-CoA synthase

Article abstract of DOI:10.1246/cl.2009.184

Two dinuclear nickel complexes (Et₄N)[Ni(mbpa)-Ni(dtc ^Et)] (1) (dtc^Et=diethyldithiocarbamate) and [Ni(dadt ^Et)-Ni(dtc^Me)](BPh₄) (2) (dtc ^Me=dimethyldithiocarbamate) have been syn

Full text of DOI:10.1246/cl.2009.184

184
Chemistry Letters Vol.38, No.2 (2009)
Cationic and Anionic Dinuclear Nickel Complexes [Ni(N2S2)Ni(dtc)]n (n ¼ ꢀ1, +1)
Modeling the Active Site of Acetyl-CoA Synthase
Yumei Song, Mikinao Ito, Mai Kotera, Tsuyoshi Matsumoto,ꢀ and Kazuyuki Tatsumiꢀ
Research Center for Materials Science, and Department of Chemistry, Graduate School of Science,
Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8602
(Received October 24, 2008; CL-081022; E-mail: i45100a@nucc.cc.nagoya-u.ac.jp)
2–
Two dinuclear nickel complexes (Et4N)[Ni(mbpa)-
O
O
O
Et
Et
S
S
Br
–
Ni(dtcEt)] (1) (dtcEt = diethyldithiocarbamate) and [Ni(dadtEt)-
Ni(dtcMe)](BPh4) (2) (dtcMe = dimethyldithiocarbamate) have
been synthesized as models for the active site of acetyl-CoA syn-
thase (ACS). Cyclic voltammograms show that each complex
exhibits a reduction wave, in which the reduction potential of
the anion 1 exhibits a significant negative shift from that of
the cation 2.
Ni
C
N
S
S
N
N
S
S
N
N
Et
Et
Ph3P
S
S
Ni
C
N
Ni
Ni
CH3CN
O
1
[Ni(mbpa)]2–
Et
+
Me
Me
S
Br
Et
Et
Ni
C
N
N
S
S
Me
N
N
S
Ph3P
S
Ni
Ni
Ni
C
N
N
S
S
S
NaBPh4/ MeOH
Me
Acetyl-CoA synthase (ACS)/carbon monoxide dehydrogen-
ases (CODH) are bifunctional metalloenzymes, playing signifi-
cant roles for CO2 fixation in various microorganisms.1,2 Crys-
tallographic results reported for ACS from Moorella themoace-
tia and Carboxydothermus hydrogenoformans have revealed that
the A-cluster, the active site of ACS, is composed of a [Fe4S4]
cluster and a dinuclear Nid–Nip unit as shown in Figure 1,3,4
where the two nickels designated as Nid and Nip occupy distal
and proximal positions to the [Fe4S4] cluster, respectively. The
geometry around Nid is square planar composed of two cysteine
sulfurs and two carboxyamide nitrogens of the tripeptide Cys–
Gly–Cys from the protein backbone. The proximal nickel ion,
Nip, carries an unidentified ligand X and the three bridging cys-
teine sulfurs, two from the aforementioned tripeptide, and one
from the [Fe4S4] cluster.5–9
Since the elucidation of the ACS crystal structure, several
thiolate-bridged dinuclear nickel complexes modeling the active
site of ACS have been reported.10 However, among these, only a
single complex [NiII(dadtEt)NiII(SCH2CH2PPh2)]þ reported by
Holm and co-workers (dadtEt = N,N0-diethyl-3,7-diazanonane-
1,9-dithiolate) has a third thiolate ligand at the Nip site.10a Re-
cently, we have found that the trinuclear cluster, [{Ni(dadtEt)}2-
Ni](NiBr4), serves as a useful precursor of dinuclear nickel com-
plexes of the type, Ni(dadtEt)Ni(X)2 and [Ni(dadtEt)Ni(L)2]2þ
(X = arenethiolates, L = tmtu, t-BuNC).11 To improve insight
into the function of the dinuclear nickel site in the A-cluster,
we have extended our studies to the dianionic dicarboxyami-
do–dithiolato nickel(II), [Ni(mbpa)]2ꢁ (H4mbpa = [N,N0-bis-
(3-methyl-3-sulfanylbutyryl)-o-phenylenediamine]),12 as a Nip
site model (see Scheme 1). The mbpa ligand has two properties
superior to the dadtEt ligand; (1) carboxyamido nitrogens of the
Et
Ni(dadtEt
2
)
Scheme 1.
mbpa ligand structurally more closely resemble the donors found
in the A-cluster than the amino donors of the dadtEt ligand, (2)
the mbpa ligand carries a 4ꢁ charge as does the Cys–Gly–Cys
ligand in the A-cluster, whereas the dadtEt ligand is dianionic.
Herein we report the synthesis of (Et4N)[Ni(mbpa)Ni(dtcEt)]
(1) (dtcEt = diethyldithiocarbamate) and [Ni(dadtEt)Ni(dtcMe)]-
(BPh4) (2) (dtcMe = dimethyldithiocarbamate), and discuss
their structures and redox properties.
(Et4N)2[Ni(mbpa)] was synthesized by the reaction of
H4mbpa and Ni(OAc)2 4H2O in the presence of KOH followed
.
by cation exchange with Et4NCl.13 The X-ray crystallography
reveals that the geometry and metric parameters around the
nickel of (Et4N)2[Ni(mbpa)] compare well with those of
Ni(dadtEt) reported previously.14 Although the bond angles
around the nickels of [Ni(mbpa)]2ꢁ and Ni(dadtEt) are somewhat
different owing to the different chelate ring-size, the nickels of
both [Ni(mbpa)]2ꢁ and Ni(dadtEt) assume a regular square-
planar geometry.
Treatment of (Et4N)2[Ni(mbpa)] with Ni(PPh3)(dtcEt)Br in
acetonitrile afforded the dinuclear nickel anion 1 in 87% yield
as green crystals (Scheme 1). A similar reaction using Ni(dadtEt)
in methanol and successive anion-exchange with NaBPh4 gave
the analogous dinuclear nickel cation 2 in 90% yield as brown
crystals.
X-ray crystallographic analysis confirms the formation of
the dinuclear nickel complexes 1 and 2 as shown in Figure 2.15
Their structures compare well with that of the dinuclear nickel
site in the A-cluster of ACS shown in Figure 1. The two
square-planar nickels of each complex are bridged by the two
thiolato sulfurs of the N2S2 ligand to form a folded Ni2S2 quad-
rangle; the dihedral angles along ꢀS(1)–ꢀS(2) vectors are 102.6
and 105.5ꢂ for 1 and 2, respectively, whereas the corresponding
angle for the dinuclear nickel site in the A-cluster is somewhat
Cys
S
Cys
X
O
S
Cys
Nid
S
Fe
S
Cys
Nip
Fe
S
Fe
N
O
S
S
Fe
S
S
Gly
N
O
S
Cys
Cys
larger, 138ꢂ. Accordingly, Ni(1)–Ni(2) distances for
1
(2.6839(8) A) and 2 (2.6706(3) A) are shorter than the value
˚ ˚
Figure 1. Drawing of the active site of ACS.
Copyright Ó 2009 The Chemical Society of Japan

Chemistry Letters Vol.38, No.2 (2009)
185
This research was supported by Grant-in-Aids for Scientific
Research (Nos. 18GS0207 and 18065013) and Nagoya Global
COE Program from the Ministry of Education, Culture, Sports,
Science and Technology, Japan. We are grateful to Prof. Roger
E. Cramer for discussions and careful reading of the manuscript.
a)
b)
S(4)
S(4)
S(3)
Ni(2)
N(2)
Ni(1)
S(3)
This paper is dedicated to Professor Ryoji Noyori on the
occasion of his 70th birthday.
S(2)
Ni(1)
Ni(2)
S(2)
N(2)
S(1)
N(1)
N(1)
S(1)
References and Notes
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3
Figure 2. Molecular structures of (a) the anion in 1 and (b) the
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E / V (vs. Ag/Ag+)
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Figure 3. Cyclic voltammograms of 1 (top) and 2 (bottom).
˚
for the A-cluster (3.0 A). Such structural differences would be
ascribed to the geometrical difference of the N2S2 ligands.
The redox behavior of 1 and 2 is of interest, because the
activation process of ACS involves a one- or two-electron
reduction of the A-cluster although the mechanism has not been
elucidated. The cyclic voltammogram of the cation 2 recorded
in MeCN exhibits an irreversible reduction process at Ea ¼
ꢁ1:42 V (vs. Ag/Agþ) (Figure 3).16 Because Ni(dadtEt) does
not show any redox event in the +0.3– ꢁ1:8 V range, this wave
would correspond to the reduction of the nickel located at the
model Nip site. The reduction wave for 1 was observed at
Ea ¼ ꢁ1:84 V in MeCN as a quasi-reversible reduction process,
which is negatively shifted from 2. This negative shift is under-
standable, considering that 1 is anionic while 2 is cationic.17 As
for 1, an additional reversible oxidation event was observed at
E1=2 ¼ þ0:10 V, which probably corresponds to the oxidation
of the nickel sitting in the mbpa ligand. This oxidation potential
is shifted positively by 0.7 V from that of mononuclear
[Ni(mbpa)]2ꢁ observed at Ep ¼ ꢁ0:6 V, because of the coordi-
nation of the electrophilic [Ni(dtcEt)]þ unit to the [Ni(mbpa)]2ꢁ
of 1.
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15 Crystallographic data for (Et4N)2[Ni(mbpa)], 1, and 2 have been de-
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In summary, we have synthesized two dinuclear nickel com-
plexes 1 and 2 modeling the ACS active site structure. These are
rare examples carrying S-donor ligands at the model Nip site.
Their structural features compare well with that of the ACS di-
nuclear nickel site, as confirmed by X-ray crystallographic anal-
ysis. Both 1 and 2 show a cyclic voltammogram reduction wave,
and their reduction potentials exhibit different values, reflecting
their relative net charges.
16 Supporting Information is also available electronically on the CSJ-
Journal Web site, http://www.csj.jp/journals/chem-lett/index.html.
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Published on the web (Advance View) February 5, 2009; doi:10.1246/cl.2009.184