Structural models for the active site of acetyl-CoA Synthase: Synthesis of dinuclear nickel complexes having thiolate, isocyanide, and thiourea on the Nip site

Article abstract of DOI:10.1021/ic801967e

The trinuclear nickel complex [{Ni(dadt^Et)}₂Ni] (NiBr₄) (dadt^Et = N,N′-diethyl-3,7-diazanonane-1,9- dithiolate) (1a), prepared by the reaction of Ni(dadt^Et) and Ni(EtOH)₄Br₂, was

Full text of DOI:10.1021/ic801967e

Inorg. Chem. 2009, 48, 1250-1256
Structural Models for the Active Site of Acetyl-CoA Synthase: Synthesis
of Dinuclear Nickel Complexes Having Thiolate, Isocyanide, and
Thiourea on the Nip Site
Mikinao Ito, Mai Kotera, Yumei Song, Tsuyoshi Matsumoto, and Kazuyuki Tatsumi*
Research Center for Materials Science, and Department of Chemistry, Graduate School of
Science, Nagoya UniVersity, Furo-cho, Chikusa-ku, Nagoya 464-8602, Japan
Received October 15, 2008
The trinuclear nickel complex [{Ni(dadtEt)}2Ni](NiBr4) (dadtEt ) N,N’-diethyl-3,7-diazanonane-1,9-dithiolate) (1a),
prepared by the reaction of Ni(dadtEt) and Ni(EtOH)4Br2, was found to serve as a useful synthetic precursor of
various dinuclear nickel complexes modeling the active site of acetyl-CoA synthase (ACS). The reactions of 1a
with 4 equiv of the potassium salts of arenethiolates in ethanol produced a series of dinuclear nickel thiolate
complexes Ni(dadtEt)Ni(SAr)2 (Ar ) Ph (2a), p-Tol (2b), 2,4,6-triisopropylphenyl (Tip) (2c)) in good yields. The
t
analogous reactions of 1a with Ag(OTf) in the presence of BuNC and (NMe2)2CS (tmtu) generated the dicationic
dinuclear nickel complexes [Ni(dadtEt)Ni(tBuNC)2](OTf)2 (3) and [Ni(dadtEt)Ni(tmtu)2](OTf)2 (4), respectively. The
molecular structures of 1a, 2a-c, 3, and 4 determined by X-ray analysis compare well with that of A-cluster in
ACS.
Introduction
Acetyl-CoA synthase (ACS)/CO dehydrogenase (CODH)
is an unique multifunctional enzyme, playing an important
role in the Wood-Ljungdahl pathway of CO2 fixation.1
While CODH catalyzes the reversible reduction of CO2 to
CO, ACS assembles acetyl-CoA from carbon monoxide,
Figure 1. Drawing of the ACS active site structure.
coenzyme A, and a methyl moiety derived from the corrinoid
iron-sulfur protein (CFeSP). Recently the crystal structures
tively. The Nid site is square planar, coordinated by two
of the ACS/CODH system from the bacteria Moorella
cysteine sulfurs and two amide nitrogens of the Cys-Gly-
thermoacetica have been determined.2,3 The ACS active site,
Cys tripeptide from the protein backbone. The two cysteine
sulfurs of this tripeptide also bind Nip, along with cysteine
denoted as the A-cluster, consists of a dinuclear nickel site
and a Fe4S4 cubane cluster formulated as [Nid{(µ-Cys-S)-
Gly-(µ-Cys-S)}Nip(X)](µ-Cys-S){Fe4(µ-Cys-S)3S4} (Figure
1), where the two nickel atoms are designated as Nid and
thiolate from the [Fe4S4] cluster and an unidentified ligand
X.3 Although crystal structures containing Cu(I)2 and Zn(II)3
at the proximal site have also been reported, recent evidence
Nip, being distal and proximal to the Fe4S4 cluster, respec-
is convincing that a nickel ion at the proximal is essential
for enzymatic activity.4 The monofunctional ACS isolated
* To whom correspondence should be addressed. E-mail: i45100a@
nucc.cc.nagoya-u.ac.jp.
from Carboxydothermus hydrogenoformans also contains
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Nip.5
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1250 Inorganic Chemistry, Vol. 48, No. 3, 2009
10.1021/ic801967e CCC: $40.75  2009 American Chemical Society
Published on Web 01/07/2009

Structural Models for the ActiWe Site of Acetyl-CoA Synthase
Since the elucidation of the ACS crystal structure, the
synthesis of the A-cluster model complex has been a
challenge for the bioinorganic chemists. The typical synthetic
method for modeling the dinuclear nickel active site reported
so far involves the reaction of square-planar Ni(N2S2) com-
plexes mimicking the Nid site with exogenous nickel
complexes bearing appropriate labile ligands. The N2S2
ligands are diaminedithiolates such as N,N’-diethyl-3,7-
diazanonane-1,9-dithiolate (dadtEt) or diamidodithiolates such
as 2,7-dioxo-3,6-diazaoctanedithiolate (ema) and a Cys-Gly-
Cys tripeptide (CGC).6,7 However, the ligand lability for the
exogenous nickels often leads to the formation of trinuclear
complexes of the type {Ni(N2S2)}2Ni.6,7a-e Thus, the nickel
complexes containing chelate diphos or terpyridine ligands
have been used as the exogenous nickel sources to stabilize
the dinuclear nickel complexes such as Ni(CGC)Ni(L) (L
) depe or dppe),7a Ni(L-655)Ni(depe),7b Ni(NpPepS)Ni(L)
(NpPepS ) N,N’-napthalenebis(o-mercaptobenzamide), L )
terpy or dppe),7e [Ni(dadtEt)Ni(dppe)]2+,7f and [Ni(Phma)Ni(dp-
pe)Me]+.7g Although these complexes model the dinuclear
nickel core of ACS, the rigid coordination of the Nip by the
multidentate ligands may interfere with binding the substrates
such as CO, Me, and thiolate in the development of ACS
model reaction. There is one example of the dinuclear nickel
model having an appended thiolate on the Nip site,
[Ni(dadtEt)Ni(SCH2CH2PPh2)][PF6] reported by Holm,7c
while in the A-cluster the Nip is bridged with the cysteine
thiolates of Ni(N2S2) unit and coordinated with an appended
third cysteine thiolate arising from a [Fe4S4] cluster. Besides,
we also recall the bimetallic Ni(II)-Ni(0) CO complex,
Ni(S2N2′)Ni(CO)2, reported by Rauchfuss, which is the first
structurally characterized complex as a possible reduced-
ACS active site model.8
Experimental Section
General Procedures. All reactions and manipulations were
conducted using standard Schlenk and vacuum line techniques or
in a glovebox under a nitrogen atmosphere. Hexane, ether,
tetrahydrofuran (THF), acetonitrile, and toluene were purified
according to the method described by Grubbs, in which the solvents
were passed over columns of activated alumina and copper catalyst
supplied by Hansen & Co. Ltd. Dichloromethane was distilled from
CaH2. Methanol and ethanol were distilled from magnesium
turnings. Deuterated solvents were dried over potassium (THF-d8),
sodium (benzene-d6), CaH2 (acetonitrile-d3, dichloromethane-d2,
chloroform-d) or molecular sieves 4 Å (dimethylsulfoxide-d6) under
nitrogen. 1H NMR spectra were recorded on a JEOL ECA-600. IR
spectra were measured on a JASCO FT/IR-410 spectrometer. UV/
vis spectra were recorded in 10 mm quarz glass cells on a JASCO
V-560 spectrometer. Electrospray ionization time-of-flight mass
spectrometry (ESI-TOF-MS) spectra were obtained from a Micro-
mass LCT TOF-MS spectrometer. Fast atom bombardment (FAB)
mass spectra were obtained on a JEOL JMS-LCMATE mass
spectrometer under the stream of high energy Xe gas, where
3-nitrobenzyl alcohol was used as the matrix. Elemental analyses
were recorded on a LECO-CHNS-932 elemental analyzer where
the crystalline samples were sealed in silver capsules under nitrogen.
The compounds Ni(dadtEt),9 Ni(EtOH)4Br2,10 [Et4N]2[Ni(S-p-
Tol)4],11 and TipSH (Tip ) 2,4,6-triisopropylphenyl)12 were
prepared according to literature procedures.
Synthesis of [{Ni(dadtEt)}2Ni][NiBr4] (1a). When an ethanol
solution (30 mL) of Ni(EtOH)4Br2 (4.00 g, 9.93 mmol) was added
to a solution of Ni(dadtEt) (3.06 g, 9.96 mmol) in ethanol (100 mL)
at room temperature, a dark green crystalline solid precipitated.
After stirring the suspension overnight, this solid was separated by
filtration and dried in vacuo to give 1a (4.35 g, 83% yield) as a
dark green crystalline powder. Crystallization from acetonitrile/
ether gave crystals suitable for X-ray structural analysis. ESI-MS
(CH3CN): m/z ) 335.9 (M2+). Anal. Calcd for C22H48Br4N4Ni4S4:
C, 25.29; H, 4.635; N, 5.367. Found: C, 24.78; H, 4.603; N, 5.272.
µeff ) 0.5 µB in CD3OD, according to the NMR method described
by Evans;13 a solution of 1a (10.0 mg) in CD3OD was prepared in
a 1.0 mL volumetric flask. A portion of this solution was transferred
into a capillary tube that was sealed and dropped into a NMR tube
containing CD3OD. The chemical shift difference of the tetram-
ethylsilane signal between the inner and the outer tubes was
measured at room temperature. From the difference in the chemical
Herein we report the synthesis of a series of dinuclear
nickel complexes, Ni(dadtEt)Ni(SAr)2 (Ar ) Ph, p-Tol, 2,4,6-
triisopropylpheny (Tip)) and [Ni(dadtEt)NiL2]2+ (L ) tBuNC,
tmtu), from the preformed trinuclear nickel cluster
[{Ni(dadtEt)}2Ni](NiBr4). These dinuclear nickel complexes
having the monodentate thiolates and donors represent new
models for the ACS active site.
1
shifts the µeff value was calculated. H NMR (CD3OD solution of
1a)14 δ 3.46-3.38 (br m, 2H, NCH2CH2S), 3.23 (dq, J ) 6.9 Hz,
14.0 Hz, 2H, CH3CH2), 3.11 (dq, J ) 6.9 Hz, 14.0 Hz, 2H,
CH3CH2), 2.99-2.91 (m, 4H, NCH2CH2CH2N), 2.62 (dd, J ) 8.5
Hz, 3.0 Hz, 2H, NCH2CH2S), 2.19-2.13 (m, 1H, NCH2CH2CH2N),
2.16 (dd, J ) 8.5 Hz, 3.0 Hz, 2H, NCH2CH2S), 2.01-1.93 (m,
1H, NCH2CH2CH2N), 2.13-2.05 (br m, 2H, NCH2CH2S), 1.41 (t,
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Commun. 2004, 1744–1745. (d) Golden, M. L.; Jeffery, S. P.; Miller,
M. L.; Reibenspies, J. H.; Darensbourg, M. Y. Eur. J. Inorg. Chem.
2004, 231–236. (e) HatlevikØ.; Blanksma, M. C.; Mathrubootham,
V.; Arif, A. M.; Hegg, E. L. J. Biol. Inorg. Chem. 2004, 9, 238–246.
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Holm, R. H. J. Am. Chem. Soc. 2005, 127, 1933–1945. (d) Duff, S. E.;
Barclay, J. E.; Davies, S. C.; Evans, D. J. Inorg. Chem. Commun.
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Davies, E. S.; McInnes, E. J. L.; Wilson, C.; Schro¨der, M. Chem.
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O’Hagan, M. J.; Yap, G. P. A.; Riordan, C. G. J. Am. Chem. Soc.
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J ) 6.9 Hz, 6H, CH3CH2). UV/vis (DMSO solution of 1a):14 λmax
/
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(14) The 1H NMR and UV/vis data were collected for the solutions of 1a.
However, 1a could be in equilibrium with {Ni(dadtEt)}NiBr2 in the
solutions (see Results and Discussion).
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Inorganic Chemistry, Vol. 48, No. 3, 2009 1251

Ito et al.
1
nm (ε) ) 482 (sh, 3.3 × 102), 425 (5.7 × 102), 301 (sh, 1.7 ×
104), 283 (2.3 × 104).
crystals. H NMR (C6D6): δ 7.24 (s, 4H, Tip), 5.57 (sep, J ) 6.8
Hz, 4H, Tip), 3.75 (dt, J ) 12.0 Hz, 4.0 Hz, 2H, NCH2CH2S),
2.96 (sep, J ) 6.8 Hz, 2H, Tip), 2.49 (dq, J ) 6.9 Hz, 14.0 Hz,
2H, CH3CH2), 2.18 (dq, J ) 6.9 Hz, 14.0 Hz, 2H, CH3CH2), 2.04
(dd, J ) 12.0 Hz, 4.0 Hz, 2H, NCH2CH2S), 1.96-1.90 (m, 2H,
NCH2CH2CH2N), 1.70 (d, J ) 6.8 Hz, 24H, Tip), 1.62 (dd, J )
12.0 Hz, 4.0 Hz, 2H, NCH2CH2S), 1.50-1.44 (m, 2H,
NCH2CH2CH2N), 1.40 (d, J ) 6.8 Hz, 12H, Tip), 1.17-1.06 (m,
1H, NCH2CH2CH2N), 0.85 (dt, J ) 12.0 Hz, 4.0 Hz, 2H,
NCH2CH2S), 0.66-0.58 (m, 1H, NCH2CH2CH2N), 0.21 (t, J )
6.9 Hz, 6H, CH3CH2). Anal. Calcd for C41H70N2Ni2S4: C, 58.86;
H, 8.433; N, 3.348. Found: C, 59.19; H, 7.754; N, 3.445.
Synthesis of [{Ni(dadtEt)}2Ni][PF6]2 (1b). To a methanol
solution of 1a (300 mg, 0.285 mmol) was added a methanol solution
of NaPF6 (100 mg, 0.595 mmol) at room temperature. The dark
gray material was separated by filtration, washed with methanol,
and dried in vacuo to give 1b (270 mg, 98% yield) as a dark gray
1
powder. H NMR (DMSO-d6): δ 3.48-3.32 (m, 2H, CH3CH2),
3.30-3.20 (m, 2H, CH3CH2), 2.84-2.54 (m, 8H, NCH2-
CH2S+NCH2CH2S), 2.36-1.86 (m, 2H, NCH2CH2CH2N), 1.70-1.48
(m, 2H, NCH2CH2CH2N), 1.10-0.80 (m, 8H, CH3CH2+NCH2-
CH2CH2N). Anal. Calcd for C22H48F12N4Ni3P2S4: C, 27.44; H,
5.024; N, 5.818. Found: C, 27.61; H, 4.942; N, 5.933.
Synthesis of [Ni(dadtEt)Ni(CNtBu)2](OTf)2 (3). To a methanol
solution (30 mL) of 1a (300 mg, 0.285 mmol) was added BuNC
Synthesis of Ni(dadtEt)Ni(SPh)2 (2a). To an ethanol suspension
(5 mL) of 1a (50 mg, 0.048 mmol) was added a solution of KSPh
(28 mg, 0.19 mmol) in ethanol (5 mL) at room temperature. The
reddish brown suspension was stirred overnight. The supernatant
liquid was removed, and the residue was extracted with dichlo-
romethane (10 mL). The solution was evaporated to give 2a (51
mg, 91% yield) as a reddish brown powder. Crystallization from
dichloromethane/hexane gave crystals suitable for X-ray structural
analysis. 1H NMR (DMSO-d6): δ 7.76-7.70 (m, 4H, Ph), 6.96-6.90
(m, 4H, Ph), 6.86-6.80 (m, 2H, Ph), 3.36 (dt, J ) 8.5 Hz, 3.0 Hz,
2H, NCH2CH2S), 3.24 (dq, J ) 6.9 Hz, 14.0 Hz, 2H, CH3CH2),
3.05 (dq, J ) 6.9 Hz, 14.0 Hz, 2H, CH3CH2), 2.78 (dd, J ) 8.5
Hz, 3.0 Hz, 2H, NCH2CH2S), 2.64-2.52 (m, 4H, NCH2CH2CH2N),
1.96-1.78 (m, 2H, NCH2CH2CH2N), 1.58 (dd, J ) 8.5 Hz, 3.0
Hz, 2H, NCH2CH2S), 1.38 (dt, J ) 8.5 Hz, 3.0 Hz, 2H,
NCH2CH2S), 0.99 (t, J ) 6.9 Hz, 6H, CH3CH2). Anal. Calcd for
C23H34N2Ni2S4: C, 47.29; H, 5.866; N, 4.795. Found: C, 47.30; H,
5.607; N, 4.416. UV/vis (DMSO): λmax/nm (ε) ) 520 (sh, 2.4 ×
102), 394 (7.6 × 102), 327 (sh, 2.9 × 104), 303 (3.2 × 104).
Synthesis of Ni(dadtEt)Ni(S-p-Tol)2 (2b). Method A. A similar
procedure as used for 2a but using KS-p-Tol gave 2b in 62% yield
as reddish brown crystals. 1H NMR (DMSO-d6): δ 7.60-7.54 (m,
4H, p-Tol), 6.76-6.70 (m, 4H, p-Tol), 3.36 (dt, J ) 8.5 Hz, 3.0
Hz, 2H, NCH2CH2S), 3.22 (dq, J ) 6.9 Hz, 14.0 Hz, 2H, CH3CH2),
3.04 (dq, J ) 6.9 Hz, 14.0 Hz, 2H, CH3CH2), 2.78 (dd, J ) 8.5
Hz, 3.0 Hz, 2H, NCH2CH2S), 2.64-2.54 (m, 4H, NCH2CH2CH2N),
2.11 (s, 6H, p-Tol), 1.96-1.78 (m, 2H, NCH2CH2CH2N), 1.58 (dd,
J ) 8.5 Hz, 3.0 Hz, 2H, NCH2CH2S), 1.38 (dt, J ) 8.5 Hz, 3.0
Hz, 2H, NCH2CH2S), 1.00 (t, J ) 6.9 Hz, 6H, CH3CH2). Anal.
Calcd for C25H38N2Ni2S4: C, 49.05; H, 6.256; N, 4.576. Found: C,
48.74; H, 6.393; N, 5.105. UV/vis (DMSO): λmax/nm (ε) ) 540
(sh, 1.0 × 102), 400 (7.6 × 103), 328 (sh, 1.4 × 104), 290 (1.9 ×
104), 287 (2.0 × 104).
t
(0.13 mL, 1.2 mmol) at room temperature. The solution was stirred
for 1 h, and then AgOTf (293 mg, 1.14 mmol) was added at room
temperature. The red suspension was stirred for 1 h. The suspension
was evaporated to dryness, and the residue was extracted with
dichloromethane (50 mL). The solution was evaporated to dryness,
and the residue was washed with ether to give 3 (303 mg, 64%
yield) as a red powder. The crystallization from dichloromethane/
hexane gave crystals suitable for X-ray structural analysis. 1H NMR
(CDCl3): δ 3.81-3.74 (m, 2H, NCH2CH2S), 3.33 (dq, J ) 6.9 Hz,
14.0 Hz, 2H, CH3CH2), 3.24 (dq, J ) 6.9 Hz, 14.0 Hz, 2H,
CH3CH2), 3.19-3.13 (m, 2H, NCH2CH2S), 2.94-2.88 (m, 2H,
NCH2CH2S), 2.50-2.46 (m, 2H, NCH2CH2S), 2.32-2.24 (m, 4H,
NCH2CH2CH2N), 1.90-1.85 (m, 2H, NCH2CH2CH2N), 1.60 (s,
t
18H, Bu), 1.26 (t, J ) 6.9 Hz, 6H, CH3CH2). ESI-MS (CH2Cl2):
m/z ) 679.3 ([M2++(OTf)-]+). IR (CH2Cl2): ν(CN)/cm-1 2228(s),
2219(s). Anal. Calcd for C23H42F6N4Ni2O6S4: C, 33.27; H, 5.100;
N, 6.748. Found: C, 32.62; H, 4.752; N, 6.795.
Synthesis of Ni(dadtEt)Ni(tmtu)2](OTf)2 (4). To a methanol
solution (30 mL) of 1a (1.00 g, 0.951 mmol) was added tetram-
ethylthiourea (503 mg, 3.80 mmol) at room temperature. The
solution was stirred for 1 h, and then AgOTf (1.00 g, 3.89 mmol)
was added at room temperature. The dark purple suspension was
stirred for a day. The suspension was evaporated to dryness, and
the residue was extracted with dichloromethane (50 mL). The
solution was evaporated to dryness, and the residue was washed
with THF to give 4 (965 mg, 53% yield) as a dark purple powder.
Crystals suitable for X-ray structural analysis were obtained by
crystallization of the powder from acetonitrile/ether. 1H NMR
(CD3CN): δ 3.37-3.32 (m, 2H, NCH2CH2S), 3.16 (dq, J ) 7.2
Hz, 14.0 Hz, 2H, CH3CH2), 3.07 (s, 24H, tmtu), 3.06 (dq, J ) 7.2
Hz, 14.0 Hz, 2H, CH3CH2), 2.90-2.82 (m, 4H, NCH2CH2S),
2.56-2.52 (m, 2H, NCH2CH2S), 2.05-1.99 (m, 4H,
NCH2CH2CH2N), 1.87-1.81 (m, 2H, NCH2CH2CH2N), 1.32 (t, J
) 7.2 Hz, 6H, CH3CH2). Anal. Calcd for C23H48F6N6Ni2O6S6: C,
29.75; H, 5.211; N, 9.052. Found: C, 29.78; H, 5.124; N, 8.790.
X-ray Structure Determinations. Crystal data and refinement
parameters for the structurally characterized complexes are sum-
marized in Table 1. Single crystals were mounted on a loop using
oil (CryoLoop, Immersion Oil type B: Code 1248, Hampton
Laboratories, Inc.). Diffraction data were collected at -100 °C
under a cold nitrogen stream on a Rigaku AFC8 equipped with a
Mercury CCD area detector (for 1a, 2c, 3, and 4) or a Rigaku RA-
Micro007 with a Saturn 70 CCD area detector (for 2a and 2b),
equipped with a graphite monochromatized Mo KR source (λ )
0.71070 Å). Data were collected on 1200 oscillation images with
an oscillation range of 0.3°. The frame data were integrated and
corrected for absorption using the Rigaku/MSC CrystalClear
program package. The structures were solved by direct methods
(SIR-92 or SIR-97) and were refined by full-matrix least-squares
Method B. To an acetonitrile solution (10 mL) of 1b (100 mg,
0.095 mmol) was added a solution of [Et4N]2[Ni(S-p-Tol)4] (85
mg, 0.10 mmol) in acetonitrile (10 mL) at room temperature. The
reddish brown solution was stirred for 12 h and evaporated in vacuo.
The solid was extracted with dichloromethane (15 mL), and the
solution was evaporated to dryness. The residue was washed with
THF (5 mL) and methanol (10 mL) and dried in vacuo to give 2b
(92 mg, 73% yield).
Method C. To an acetonitrile solution (10 mL) of 1b (100 mg,
0.095 mmol) was added a solution of [Et4N](S-p-Tol) (53 mg, 0.21
mmol)) in acetonitrile (10 mL) at room temperature. After stirring
for 12 h, the solution was evaporated to dryness and the residue
was extracted with dichloromethane (15 mL). The solution was
evaporated to dryness, and the residue was washed with methanol
(10 mL) and dried in vacuo to give 2b (55 mg, 96% yield).
Synthesis of Ni(dadtEt)Ni(STip)2 (2c). A similar procedure as
used for 2a but using KSTip gave 2c in 65% yield as reddish brown
1252 Inorganic Chemistry, Vol. 48, No. 3, 2009

Structural Models for the ActiWe Site of Acetyl-CoA Synthase
Table 1. Crystallographic Data for Complexes
1a
2a
2b
2c
3 ·CH2Cl2
4
formula
Fw
C22H48N4S4Br4Ni4
1051.30
C23H29N2S4Ni2
579.14
C25H38N2S4Ni2
612.23
C41H70N2S4Ni2
836.66
C23H42N4S4O6F6Ni2 ·CH2Cl2
915.17
C23H48N6S6 F6Ni2
928.42
crystal system
space group
a, Å
b, Å
c, Å
triclinic
P1
triclinic
P1
monoclinic
P21/n
12.112(8)
11.209(7)
20.902(14)
monoclinic
P21/n
11.765(4)
24.221(8)
15.828(6)
monoclinic
P21/n
8.7723(16)
19.147(4)
triclinic
P1
j
j
j
10.7952(16)
11.1407(18)
15.375(2)
105.9193(19)
93.8777(15)
98.975(2)
1744.5(5)
2
10.4260(14)
11.0774(16)
11.8118(19)
82.957(7)
78.296(6)
71.586(5)
1264.9(3)
2
12.3351(1)
12.5861(1)
14.0789(1)
69.447(6)
82.509(7)
68.182(7)
1900.03(12)
2
22.968(4)
R, deg
ꢀ, deg
102.783(10)
106.781(5)
93.4050(19)
γ, deg
V, Å3
2768(3)
4
4318(3)
4
3851.1(12)
4
Z
Dcalcd, g/cm3
2θmax, deg
no. of unique rflns
no. of obsd rflns
no. of parameters
GOF (F2)
2.001
54.96
7952
20681
347
1.073
0.0360
0.0874
b
1.520
54.96
5556
10255
306
1.061
0.0335
0.0914
2
1.469
54.96
6315
21850
299
1.194
0.0614
0.1273
2
1.287
54.96
9864
33672
443
1.155
0.0427
0.0918
1.578
54.96
8807
29718
434
1.052
0.0377
0.0950
1.623
54.96
8280
14760
497
1.085
0.0304
0.0766
a
R1
wR2
b
a R1 ) ∑||Fo| - |Fc||/∑|Fo|. wR2 ) {∑[w(Fo - Fc2)2]/∑w(Fo )2}1/2
.
Scheme 1
Scheme 2
on F2 using SHELXL-9715 in the Rigaku/MSC CrystalStructure
program package. Anisotropic refinement was applied to all non-
hydrogen atoms except for the disordered atoms, and all hydrogen
atoms were put at calculated positions. A phenyl group of 2a was
disordered over two positions in a 6:4 ratio. An anion of 4 was
disordered over two positions in a 1:1 ratio. Additional crystal-
lographic data are given in the Supporting Information.
site bearing thiolate coordinated entities on the Nip site and
can be compared with the thiolate-bridging tetranuclear
nickel complex, [{Ni(LR-S2N2)}Ni(S-p-Tol)]2[PF6]2, reported
by Holm et al.7b The sharp H NMR signals observed for
1
2a-c in DMSO-d6 are indicative of diamagnetism, which
shows that both nickel centers of each dinuclear complex
have a square planar geometry. The two aryl groups of each
complex are equivalent, so that the molecules should have
Results and Discussion
Synthesis of Dinuclear Nickel Complexes Having
Thiolates at the Model Nip Site. We chose Ni(dadtEt) as a
building block of dinuclear nickel complexes modeling the
ACS dinuclear nickel site and examined the reaction with
NiBr2(EtOH)4. When the reaction was conducted in ethanol,
a dark green crystalline powder precipitated immediately.
This dark green product was identified as the trinuclear nickel
complex [{Ni(dadtEt)}2Ni][NiBr4] (1a) by X-ray structural
analysis (Scheme 1), in which the trinuclear nickel cation is
the same as that of [{Ni(dadtEt)}2Ni][Ni(PPh3)Cl3]2 reported
by Holm and co-workers.7c
Although the desired dinuclear nickel complex could not
be isolated from the Ni(dadtEt) + NiBr2(EtOH)4 reaction
system, 1a was found to serve as a convenient precursor for
the preparation of dinuclear nickel complexes. The reactions
of 1a with a series of potassium arenethiolates in ethanol
afforded Ni(dadtEt)Ni(SAr)2 (Ar ) Ph (2a), Ar ) p-Tol (2b),
Ar ) Tip (2c)) as reddish brown precipitates, and the
products were isolated in 62-91% yields based on Ni of 1a
(Scheme 2). These complexes are models for the ACS active
1
mirror symmetry. The absence of change in the H NMR
spectra of 2a-c from 25 to 80 °C shows their thermal
stability.
The high yields of 2a-c indicate that both tetrabromonick-
elate (2-) and the trinuclear complex dication of 1a must be
involved in the transformation from 1a to the dinuclear nickel
complexes. Accordingly, three possible pathways can be
considered for this intriguing transformation, as summarized
in Scheme 3. One conceivable mechanism is the formation of
{Ni(dadtEt)}NiBr2 via a ligand redistribution process of 1a,
before any reaction with KSAr occurs (Route 1 in Scheme 3).
1
The H NMR spectrum and the magnetic moment estimated
by Evans method13 for 1a in CD3OD are indicative for the
{Ni(dadtEt)}NiBr2 formation. The magnetic moment shows
considerably smaller value (µeff ) 0.5 µB) than the expected
value for the tetrahedral [NiBr4]2-.16 Thus, the 1H NMR signals
are reasonably sharp, in which a major set of signals assignable
to a dadtEt ligand is different from that observed for
[{Ni(dadtEt)}2Ni][PF6]2 (1b) (see below). These results could
(16) The magnetic moment for (NEt4) 2[NiBr4] in the solid state was
reported as µeff ) 3.80 µB (298 K), see Sacconi, L.; Ciampolini, M.;
Campogli, U. Inorg. Chem. 1965, 4, 407–409.
(15) Sheldrick, G. M. SHELX97; University of Go¨ttingen; Go¨ttingen,
Germany, 1997.
Inorganic Chemistry, Vol. 48, No. 3, 2009 1253

Ito et al.
Scheme 3
Scheme 4
suggest that 1a and {Ni(dadtEt)}NiBr2 are in equilibrium
assuming diamagnetism of {Ni(dadtEt)}NiBr2, and {Ni(dadtEt)}-
NiBr2 could be a majority in CD3OD. Another possible
mechanism is that KSAr reacts first with [NiBr4]2- of 1a to
generate [{Ni(dadtEt)}2Ni][Ni(SAr)4], and then a thiolate transfer
occurs from [Ni(SAr)4]2- to [{Ni(dadtEt)}2Ni]2+ giving rise to
Ni(dadtEt)Ni(SAr)2 (Route 2). Alternatively, 2 equiv of KSAr
could directly attack the trinuclear complex cation to form Ni-
(dadtEt)Ni(SAr)2, with concomitant liberation of Ni(dadtEt) and
K2[NiBr4]. Subsequently, 2 equiv of KSAr may react with
K2[NiBr4] and Ni(dadtEt), leading to Ni(dadtEt)Ni(SAr)2 and 4
equiv of KBr (Route 3).
extraction with CH2Cl2 followed by washing of the crude
product with methanol. Formation of Ni(dadtEt) was noticed
in this methanol solution. Thus, p-toluenethiolate can react
directly with [{Ni(dadtEt)}2Ni]2+ to afford the dinuclear
complex 2b and Ni(dadtEt). This transformation corresponds
to Route 3, suggesting that the mechanism involving Route
3 is as plausible as Route 2. It may be that all of the three
routes in Scheme 3 are operating in the reactions of 1a with
potassium arenethiolates to give 2a-c in high yields.
It should be noted here that contrary to arenethiolates, the
reactions of 1a with alkylthiolates such as ethanethiolate or
t-butanethiolate did not produce the desired dinuclear
complexes. These reactions led to formation of Ni(dadtEt)
and the concomitant precipitation of uncharacterizable Ni/S
containing compounds, which are insoluble to common
organic solvents. We attribute this to the stronger S-donor
property of the alkylthiolates than those of arenethiolates and
the thiolate sulfur atoms in the Ni(dadtEt) complex, which
would cause the displacement of Ni(dadtEt) of 1a to produce
insoluble oligomeric/polymeric nickel alkylthiolates.
To gain insight into the mechanism, [{Ni(dadtEt)}2Ni]-
[PF6]2 (1b) was synthesized by anion exchange of 1a with 2
equiv of NaPF6, and the reactions of 1b with [Et4N]2[Ni(S-
p-Tol)4] and [Et4N](S-p-Tol) were examined. Upon treating
1b with 1 equiv of [Et4N]2[Ni(S-p-Tol)4] in acetonitrile,
Ni(dadtEt)Ni(S-p-Tol)2 (2b) was obtained in 73% yield based
on nickel (Scheme 4). This result clearly indicates that facile
ligand redistribution occurs between [Ni(S-p-Tol)4]2- and
[{Ni(dadtEt)}2Ni]2+ and supports the mechanism via Route
2 in Scheme 3. On the other hand, 2 equiv of [Et4N](S-p-
Tol) was also found to react with 1b in acetonitrile, from
which 2b was isolated in 96% yield on the basis of
p-toluenethiolate (Scheme 4). The product was purified by
Synthesis of Cationic Dinuclear Nickel Complexes
Having Neutral Ligands at the Model Nip Site. Cationic
dinuclear nickel complexes ligated by tBuNC or tetramethylth-
iourea (tmtu) at the Nip site could also be synthesized from 1a.
When a methanol solution of 1a was treated with AgOTf (4
1254 Inorganic Chemistry, Vol. 48, No. 3, 2009

Structural Models for the ActiWe Site of Acetyl-CoA Synthase
Scheme 5
equiv) in the presence of tBuNC, the color of the solution turned
from dark green to red, and [Ni(dadtEt)Ni(CNtBu)2](OTf)2 (3)
was isolated in 64% yield as a red powder. The tmtu analogue,
[Ni(dadtEt)Ni(tmtu)2](OTf)2 (4), was obtained in 56% yield as
a dark purple powder via a similar procedure (Scheme 5). As
is the case of the reactions between 1a and potassium salts of
arenethiolates, the [NiBr4]2- of 1a appears to contribute to the
formation of 3 and 4. Thus, a mechanism equivalent in Scheme
3 may be applied to the transformation from 1a to 3 or 4.
The structures of 3 and 4, revealed by X-ray crystal-
Figure 3. ORTEP drawing of the complex cation [Ni(dadtEt)Ni(CNtBu)2]2+
(3). Thermal ellipsoids are shown at 50% probability.
t
lography, show two BuNC ligands or two tmtu ligands
coordinated to the Nip site of the dinuclear structures,
respectively. The IR spectrum of 3 shows two characteristic
bands at 2228 and 2219 cm-1, which are attributable to the
CN stretch of tBuNC. These are significantly shifted to higher
frequencies from that of free tBuNC (2136 cm-1) as has been
reported for other nickel(II)-isocyanide complexes.17
Molecular Structures and Structural Comparison
with A-cluster. The structures of 1a, 2a, 2b, 2c, 3, and 4
were elucidated by X-ray crystallography, and those of 2a,
3, and 4 are shown in Figures 2, 3, and 4, respectively. The
structures of 2b and 2c are very similar to that of 2a except
for the identity of arenethiolates on Ni(2), and the structure
of the trinuclear dication of 1a has been reported7c (see
Supporting Information). Selected bond lengths and angles
of 1a, 2a, 2b, 2c, 3, and 4 are listed in Table 2 together
with the structural parameters reported for the A-clusters in
ACSMt.
Figure 4. ORTEP drawing of the complex cation [Ni(dadtEt)Ni(tmtu)2]2+
(4). Thermal ellipsoids are shown at 50% probability.
and the Ni · · · Ni are consequently separated (2.718-2.830
Å). The small fold of the Ni2S2 quadrangles and thus shorter
Ni · · · Ni distances compared with these for the A-cluster
would be ascribed to the geometrical difference of the N2S2
ligands.
Both nickel centers of each complex display a square
planar geometry as is common for Ni(II) complexes. The
two coordination planes are folded along the µS-µS vector.
The dihedral angle defined by the two Ni(µ-S)2 planes in
each complex falls in a relatively narrow range of 105-115°,
The bond lengths around Ni(1) are nearly identical among
these model complexes and their Ni(1)-µS bonds are a little
shorter than those of the A-cluster. The bond angles around
Ni(1) are varied according to the lengths of the carbon chains
in the N2S2 ligand. The dadtEt ligands in these complexes
show a common geometrical feature, namely, that the
ethylene carbons bridging S and N, in the Ni(1)SCCN
pentagons of dadtEt with an envelope conformation, are all
located above the Ni(1)S2N2 plane. The Ni(2) atom coordi-
nates at the dadtEt sulfurs also from above the Ni(1)S2N2
plane, probably because of a favorable interaction with the
S lone pairs, in turn determined by the conformation of the
dadtEt ligand. A similar conformation of dadtEt had been rep-
orted for [Ni(dadtEt)Ni(SCH2CH2PPh2)][PF6] and [Ni(dadtEt)-
Ni(dppe)][PF6]2, in which the folded geometry of the Ni2S2
core, the square planar geometry of the nickels, and the
metric parameters around the nickels also compare well with
those for 2a-c, 3, and 4.7c,f
Contrary to the insignificant geometrical differences at
Ni(1) among models, the Ni(2)-µS bond lengths vary
depending on the ligands trans to them. In particular, the
Ni(2)-µS bonds of 3 are significantly shorter than 2a-c
Figure 2. Oak Ridge Thermal Ellipsoid Plot (ORTEP) drawing of
Ni(dadtEt)Ni(SPh)2 (2a). Thermal ellipsoids are shown at 50% probability.
The phenyl ring bonded to S(3) was modeled with two disordered
components in a 60:40 ratio, and the major component is shown.
Inorganic Chemistry, Vol. 48, No. 3, 2009 1255

Ito et al.
Table 2. Selected Bond Distances (Å) and Angles (deg) for 1a, 2a, 2b, 2c, 3, 4, and A-cluster
b
distance/angle
1aa
2a
2b
2c
3
4
A-clusterMt
Ni(1)-N(1)
1.999
1.989
2.176
2.171
2.193
2.193
1.9919(18)
2.0012(19)
2.1648(7)
2.1716(6)
2.2437(7)
2.2258(7)
2.1763(7)
2.1930(8)
2.7918(5)
101.14(7)
89.30(6)
89.66(5)
79.57(2)
76.75(2)
89.81(3)
100.40(2)
93.29(3)
109.5
1.983(3)
1.992(3)
1.983(2)
1.9933(16)
2.1623(5)
2.1712(6)
2.2604(5)
2.2381(6)
2.2154(6)
2.1751(5)
2.7237(3)
100.20(7)
90.01(4)
90.11(6)
79.56(2)
76.10(2)
91.63(2)
103.58(2)
90.11(2)
104.8
1.9790(18)
1.9840(19)
2.1636(6)
2.1666(5)
2.1919(5)
2.2062(5)
1.851(2)
1.848(2)
2.7604(5)
102.34(7)
88.89(5)
89.24(5)
79.26(2)
77.801(19)
95.28(7)
96.09(7)
90.81(10)
109.6
1.9833(14)
1.989(2)
2.1606(6)
2.1651(4)
2.2247(4)
2.2166(5)
2.2079(7)
2.2008(4)
2.7178(3)
101.49(7)
89.61(6)
89.76(4)
78.68(2)
76.254(19)
91.98(2)
97.65(2)
94.145(19)
105.2
2.00
1.97
2.22
2.25
2.35
2.14
2.34
2.38
3.04
84
105
84
87
87
106
81
Ni(1)-N(2)
Ni(1)-S(1)
2.1613(11)
2.1723(11)
2.2449(11)
2.2255(11)
2.1755(13)
2.1899(12)
2.7363(6)
100.78(14)
89.80(10)
89.98(10)
79.21(4)
Ni(1)-S(2)
Ni(2)-S(1)
Ni(2)-S(2)
Ni(2)-L(1)c
Ni(2)-L(2)d
Ni(1)-Ni(2)
2.830
101.85
88.68
88.93
80.04
79.11
100.89
N(1)-Ni(1)-N(2)
N(1)-Ni(1)-S(1)
N(2)-Ni(1)-S(2)
S(1)-Ni(1)-S(2)
S(1)-Ni(2)-S(2)
S(1)-Ni(2)-L(1)c
S(2)-Ni(2)-L(2)d
L(1)-Ni(2)-L(2)c, d
76.34(4)
91.79(4)
97.82(4)
94.86(4)
86
138
e
Ni(1)S2/Ni(2)S2
115.2
105.9
a The metric parameters are averaged between the two chelates of the Ni(dadtEt) units. A-cluster from M. thermoacetica.3 c L(1) ) S(3) for 2a, 2b, 2c,
and 4, L(1) ) C(12) for 3, and L(1) ) S for A-cluster. d L(2) ) S(4) for 2a, 2b, 2c, and 4, L(2) ) C(17) for 3, and L(2) ) X for A-cluster shown in Figure
1. e Dihedral angle.
b
which have arenethiolates, indicating the weaker trans
influence of BuNC than that of the thiolates. Since the
of Ni(2)-S(3) in complex 2a-c are shorter than that of
A-cluster, simply because the cysteine sulfur is bridging
between Ni(2) and an Fe atom of the [Fe4S4] cluster in the
A-cluster.
t
corresponding Ni(2)-µS bonds of 4 are also shorter than
2a-c but a lesser extent than 3, tmtu is evidently a stronger
donor than tBuNC. Although the Ni(2)-µS bond lengths are
varied, they are all longer than the Ni(1)-µS bonds. Thus,
the macrocyclic dadtEt ligand is tightly bound to Ni(1). A
notable difference between these models and A-cluster is
found in the Ni(2)-S(1) bond distances. The model com-
plexes have shorter Ni(2)-S(1) bond distances compared
with that of the A-cluster, which may indicate the stronger
trans-influence of the unidentified ligand X. The bond lengths
Acknowledgment. This research was financially supported
by Grant-in-Aids for Scientific Research (No. 18GS0207 and
18065013) 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.
Supporting Information Available: X-ray crystallographic data
for 1a, 2a-c, 3, and 4 are given in CIF format. This material is
available free of charge via the Internet at http://pubs.acs.org.
(17) (a) Singleton, E.; Oosthuizen, H. E. AdV. Organomet. Chem. 1984,
22, 209. (b) Wang, R.; Groux, L. F.; Zargarian, D. Organometallics
2002, 21, 5531–5539. (c) Braun, T.; Blo¨cker, B.; Schorlemer, V.;
Neumann, B.; Stammler, A.; Stammler, H.-G. J. Chem. Soc., Dalton
Trans. 2002, 2213–2218.
IC801967E
1256 Inorganic Chemistry, Vol. 48, No. 3, 2009