Synthetic analogues of the active site of the A-cluster of acetyl coenzyme A synthase/CO dehydrogenase: Syntheses, structures, and reactions with CO

Article abstract of DOI:10.1021/ic0520465

Two metallosynthons, namely (Et₄N)₂[Ni(NpPePS)] (1) and (Et₄N)₂[Ni(PhPepS)] (2) containing carboxamido-N and thiolato-S as donors have been used to model the bimetallic M _p-Ni_d subsite of the A-cluster of the enzyme acetyl coenzyme A synthase/CO dehydrogenase. A series of sulfur-bridged Ni/Cu dinuclear and trinuclear complexes (3-10) have been synthesized to explore their redox properties and affinity of the metal centers toward CO. The structures of (Et₄N)₂[Ni(PhPepS)] (2), (Et₄N)[Cu(neo) Ni(NpPePS)]·0.5Et₂O·0.5H₂O (3·0.5Et₂O·0.5H₂O), (Et₄N)[Cu- (neo)Ni(PhPepS)]·H₂O (4·H₂O), (Et ₄N)₂[Ni{Ni(NpPepS)}₂]·DMF (5·DMF), (Et₄N)₂[Ni(DMF)₂{Ni(NpPepS)} ₂]·3DMF (6·3DMF), (Et₄N)₂[Ni(DMF) ₂(Ni(PhPePS)}₂] (8), and [Ni(dppe)Ni(PhPepS)] ·CH₂Cl₂ (10·CH₂Cl₂) have been determined by crystallography. The Ni_d mimics 1 and 2 resist reduction and exhibit no affinity toward CO. In contrast, the sulfur-bridged Ni center (designated Ni_C) in the trinuclear models 5-8 are amenable to reduction and binds CO in the Ni(I) state. Also, the sulfur-bridged Ni_C center can be removed from the trimers (5-8) by treatment with 1,-10-phenanthroline much like the labile Ni from the enzyme. The dinuclear Ni-Ni models 9 and 10 resemble the Ni_p-Ni _d subsite of the A-cluster more closely, and only the modeled Ni _p site of the dimers can be reduced. The Ni(I)-Ni(II) species display EPR spectra typical of a Ni(I) center in distorted trigonal bipyramidal and distorted tetrahedral geometries for 9_red and 10_red, respectively. Both species bind CO, and the CO-adducts 9_red-CO and 10_red-CO display strong ν_co at 2044 and 1997 cm ^-1, respectively. The reduction of 10 is reversible. The CO-affinity of 10 in the reduced state and the ν_co value of 10 _red-CO closely resemble the CO-bound reduced A-cluster (ν_co = 1996 cm^-1).

Full text of DOI:10.1021/ic0520465

Inorg. Chem. 2006, 45, 3424−3436
Synthetic Analogues of the Active Site of the A-Cluster of Acetyl
Coenzyme A Synthase/CO Dehydrogenase: Syntheses, Structures, and
Reactions with CO
Todd C. Harrop,† Marilyn M. Olmstead,‡ and Pradip K. Mascharak*,†
Department of Chemistry and Biochemistry, UniVersity of California,
Santa Cruz, California 95064, and Department of Chemistry,
UniVersity of California, DaVis, California 95616
Received November 28, 2005
Two metallosynthons, namely (Et4N)2[Ni(NpPepS)] (1) and (Et4N)2[Ni(PhPepS)] (2) containing carboxamido-N and
thiolato-S as donors have been used to model the bimetallic Mp Nid subsite of the A-cluster of the enzyme acetyl
coenzyme A synthase/CO dehydrogenase. A series of sulfur-bridged Ni/Cu dinuclear and trinuclear complexes
(3 10) have been synthesized to explore their redox properties and affinity of the metal centers toward CO. The
structures of (Et4N)2[Ni(PhPepS)] (2), (Et4N)[Cu(neo)Ni(NpPepS)] 0.5Et2O 0.5H2O (3 0.5Et2O 0.5H2O), (Et4N)[Cu-
(neo)Ni(PhPepS)] H2O (4 H2O), (Et4N)2[Ni Ni(NpPepS) DMF (5 DMF), (Et4N)2[Ni(DMF)2 Ni(NpPepS) 3DMF
(6 3DMF), (Et4N)2[Ni(DMF)2 Ni(PhPepS) 2] (8), and [Ni(dppe)Ni(PhPepS)] CH2Cl2 (10 CH2Cl2) have been determined
by crystallography. The Nid mimics 1 and 2 resist reduction and exhibit no affinity toward CO. In contrast, the
sulfur-bridged Ni center (designated NiC) in the trinuclear models 5 8 are amenable to reduction and binds CO in
the Ni(I) state. Also, the sulfur-bridged NiC center can be removed from the trimers (5 8) by treatment with 1,-
10-phenanthroline much like the “labile Ni” from the enzyme. The dinuclear Ni Ni models 9 and 10 resemble the
Nip Nid subsite of the A-cluster more closely, and only the modeled Nip site of the dimers can be reduced. The
Ni(I) Ni(II) species display EPR spectra typical of a Ni(I) center in distorted trigonal bipyramidal and distorted
−
−
‚
‚
‚
‚
‚
‚
{
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]
2
‚
‚
{
} ]‚
2
‚
{
}
‚
‚
−
−
−
−
−
tetrahedral geometries for 9red and 10red, respectively. Both species bind CO, and the CO-adducts 9red-CO and
10red-CO display strong νco at 2044 and 1997 cm-1, respectively. The reduction of 10 is reversible. The CO-affinity
of 10 in the reduced state and the νco value of 10red-CO closely resemble the CO-bound reduced A-cluster (νco )
1996 cm-1).
Introduction
CoA is converted into cell carbon or respired as acetate
depending on the metabolic needs of the cell. This enzyme
is present in a number of anaerobic bacteria including
acetogens, methanogens, and sulfate-reducers that utilize the
Wood-Ljungdahl pathway for autotrophic carbon fixation.3
Indeed, ACS/CODH has been implicated in the chemoau-
totrophic origin of life in which primitive organisms con-
sumed CO or CO2 from volcanic or hydrothermal sites for
the formation of carbon-carbon bonds.4 Interest in ACS/
CODH stems from its unusual metallocluster active sites,
its role in the global carbon cycle (reducing the levels of
gaseous pollutants such as CO2), and the reactions it catalyzes
Acetyl coenzyme A synthase/carbon monoxide dehydro-
genase (ACS/CODH) is a bifunctional metalloenzyme
that catalyzes two important biological reactions, namely
the reversible reduction of CO2 into CO (CODH activity)
and the synthesis of acetyl coenzyme A (acetyl CoA) from
CO, CH3 from a methylated corrinoid iron-sulfur protein,
and the thiol CoA (ACS activity).1,2 Once formed, acetyl
* To whom correspondence should be addressed. E-mail:
pradip@chemistry.ucsc.edu. Fax: + 1-831-459-2935. Tel: + 1-831-459-
4251.
† University of California, Santa Cruz.
‡ University of California, Davis.
(1) (a) Ragsdale, S. W. Crit. ReV. Biochem. Mol. Biol. 2004, 39, 165-
195. (b) Ragsdale, S. W.; Kumar, M. Chem. ReV. 1996, 96, 2515-
2539.
(3) Wood, H. G.; Ljungdahl, L. G. Variation in Autotrophic Life;
Academic Press: New York, 1991.
(4) Huber, C.; Wa¨chtersha¨user, G. Science 1997, 276, 245-247.
(2) Lindahl, P. A. Biochemistry 2002, 41, 2097-2105.
3424 Inorganic Chemistry, Vol. 45, No. 8, 2006
10.1021/ic0520465 CCC: $33.50
© 2006 American Chemical Society
Published on Web 03/14/2006

Analogues of the ActiWe Site of the A-Cluster of ACS/CODH
utilizing well-known organometallic ligands such as CO and
CH3, analogous to the industrial Monsanto acetic acid
process.
Although a large volume of spectroscopic and biochemical
data was available for the enzyme for some time,1,2 the site
of acetyl CoA synthesis (A-cluster) has come under intense
scrutiny following the publication of three high-resolution
crystal structures.5-7 The A-cluster of ACS/CODH has been
shown to exist in two different oxidation states, Aox (S ) 0)
and Ared-CO (S ) 1/2), the one electron reduced CO-adduct
formed under CO atmosphere. The paramagnetic Ared-CO
state is readily identified by a strong rhombic EPR signal (g
) 2.08, 2.07, and 2.03) that exhibits dipolar broadening when
isotopically substituted with 61Ni, 57Fe, or 13CO (hence
referred to as the NiFeC signal).1,8 In addition, Ared-CO
displays a strong band in its IR spectrum at 1996 cm-1 (νco)
consistent with a terminally bound CO molecule.9 Addition
Figure 1. Schematic of the A-cluster site of ACS/CODH from Moorella
thermoacetica. Mp: Ni(II), Cu(I), or Zn(II); L is a nonprotein ligand.
first structure of ACS/CODH reported by Drennan and co-
workers revealed a homodimeric R2â2 protein whose active
site is relatively unexposed to solvents and contains a trio
of different metals present at the A-cluster.5 The A-cluster
in the Drennan structure consists of an Fe4S4 cubane bridged
through one Cys-S residue to a bimetallic site that contains
a square-planar Ni(II) (Nid, distal to Fe4S4) ion with N2S2
coordination derived from two backbone carboxamido ni-
trogens and two Cys-S residues. The Nid site is further
bridged through two Cys-S donors to a tetrahedral Cu(I) (Mp,
proximal to Fe4S4) center. A fourth nonprotein ligand is also
bound to Cu(I) to complete the coordination sphere (Figure
1). The second structure by Fontecilla-Camps and co-
workers, however, revealed a very different A-cluster site.6
First, the R2â2 quaternary structure is no longer symmetric
and consists of an RcââRï structure in which one of the
R-subunits (Rï) is more open and exposed to solvent. In the
Ao-cluster of Rï, a square-planar Ni(II) ion occupies the Mp
site that is ∼20 Å removed from a closed CO tunnel. Quite
in contrast, the other R subunit (Rc) is closed off to solvent
and a tetrahedral Zn(II) ion resides at the Mp site (Figure 1).
This Ac-cluster is located at the end of an open hydrophobic
CO tunnel from the C-cluster. The discrepancy in the
structures of the A-cluster from the same enzyme triggered
an intense debate regarding the identity of the true catalytic
metal ion at the Mp site. The debate has recently subsided
after careful biochemical11a,12,13 and computational studies.14,15
It is now evident that Ni at the Mp site is required for the
ACS activity. A very recent structural study on an ACS/
CODH from the hydrogenogenic bacterium Carboxydother-
mus hydrogenoformans has also revealed the presence of Ni
at the Mp site.7
+
of CH3 to CO-treated ACS/CODH affords a diamagnetic
+
state, although the order of CO and CH3 binding is still
debatable.10 Titration of ACS/CODH with the bidentate
chelator 1,10-phenanthroline (phen) results in the removal
of ∼30% of the Ni present in the enzyme.11 Such removal
of “labile Ni” abolishes the NiFeC signal and also shuts down
acetyl CoA synthesis with no effect on CODH activity.
Reconstitution of phen-treated enzyme with NiCl2 replenishes
both the NiFeC signal and synthase activity.11 These results
strongly suggest that “labile Ni” is a requirement for ACS
activity.
Crystallographic studies on ACS/CODH from the aceto-
genic bacterium Moorella thermoacetica (formerly known
as Clostridium thermoaceticum) have revealed some interest-
ing and unexpected features never seen before in any
metalloenzyme. The overall R2â2 protein comprises several
metalloclusters in the different subunits.5,6 The â subunits
at the center of the protein contain the B, C, and D clusters,
the site of CODH activity (C-cluster). The R-subunits, located
at the terminal ends of the protein, contain the A-cluster,
the site responsible for acetyl CoA formation. Interestingly,
the structure of the A-cluster reported by two separate groups
turned out to be quite different even though the enzyme was
isolated from the same organism (M. thermoacetica). The
The extent to which the unusual coordination architecture
of the A-cluster dictates its ability to assemble acetyl CoA
is still an unanswered question. The presence of carboxa-
mido-N donors at the Nid site is quite uncommon in biology.
At this time, coordination of deprotonated carboxamido-N
has only been observed in the oxidized P-cluster of nitro-
genase,16 nitrile hydratase17 (which contains a similar Cys-
(5) Doukov, T. I.; Iverson, T. M.; Seravalli, J.; Ragsdale, S. W.; Drennan,
C. L. Science 2002, 298, 567-572.
(6) Darnault, C.; Volbeda, A.; Kim, E. J.; Legrand, P.; Verne`de, X.;
Lindahl, P. A.; Fontecilla-Camps, J. C. Nat. Struct. Biol. 2003, 10,
271-279.
(7) Svetlitchnyi, V.; Dobbek, H.; Meyer-Klaucke, W.; Meins, T.; Thiele,
B.; Ro¨mer, P.; Huber, R.; Meyer, O. Proc. Natl. Acad. Sci. U.S.A.
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C. V.; Lindahl, P. A.; Mu¨nck, E. J. Am. Chem. Soc. 1997, 119, 8301-
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Inorganic Chemistry, Vol. 45, No. 8, 2006 3425

Harrop et al.
As part of our continuing efforts on modeling the bimetal-
lic Mp-Nid portion of the A-cluster of ACS, we describe
herein the syntheses and properties of several di/trinuclear
metal complexes utilizing the dicarboxamido-dithiolato Ni-
(II) metallosynthons (Et4N)2[Ni(NpPepS)] (1)26 and (Et4N)2-
Figure 2. Structures of (a) [{Ni(CO)2}{NiS2N′2}]2- and (b) [Ni(CGC)-
Ni(dRpe)].
X-Cys metal-binding motif as the Nid site), and most
recently in Ni-SOD.18 Since the publication of the first
structure of ACS/CODH, several low-molecular-weight
models of the ACS site have been synthesized and studied
to determine the intrinsic properties of the metal-containing
active site(s).19-25 In these pursuits, researchers have focused
mostly on the bimetallic Mp-Nid site of ACS and ignored
the Fe4S4 portion (unlikely site of substrate binding). For
example, Rauchfuss and co-workers have synthesized the
model complex [{Ni(CO)2}{NiS2N′2}]2- (structure a, Figure
2) with two terminal CO ligands bound to the bridged Ni
center in the 0 oxidation state.24 This complex was the first
example of a structurally characterized, mixed-valence,
sulfur-bridged, dinuclear Ni model containing carboxa-
mido-N coordination that resembles the CO-bound form of
the enzyme. More recently, Riordan and co-workers have
employed the metallopeptide unit [Ni(CGC)]2- to synthesize
biologically relevant Ni-Ni models such as [Ni(CGC)Ni-
(dRpe)] (structure b, Figure 2).20a Although phosphine donors
are not present in the enzyme, they do allow for more
favorable reduction of the Nip site of the model to the Ni(I)
state and binding of CO (as shown by electrochemistry).
However, none of the models from this study has been
characterized further by structural and spectroscopic (such
as EPR, FTIR) studies. Clearly, more model complexes are
required to establish the properties of the active site(s) of
the ACS A-cluster and what implications these have on the
overall mechanism of acetyl CoA synthesis.
[Ni(PhPepS)] (2) reported by us in preliminary accounts.27
The redox behavior of two Cu(I)-Ni(II) models, namely
(Et4N)[Cu(neo)Ni(NpPepS)] (3) and (Et4N)[Cu(neo)Ni-
(PhPepS)] (4) clearly demonstrate that the catalytically active
A-cluster cannot utilize Cu(I) at the Mp site. The four
trinuclear models (Et4N)2[Ni{Ni(NpPepS)}2] (5),27b (Et4N)2-
[Ni(DMF)2{Ni(NpPepS)}2] (6),27b (Et4N)2[Ni{Ni(PhPepS)}2]
(7), and (Et4N)2[Ni(DMF)2{Ni(PhPepS)}2] (8) and the two
dinuclear models [Ni(terpy)Ni(NpPepS)] (9)27a and [Ni-
(dppe)Ni(PhPepS)] (10)27a provide the opportunity to study,
for the first time, a series of complexes with variable donor
sets and coordination geometries at the bridged Ni(II) center
(Nip mimics). In this paper, we report the results of redox
studies and CO binding at the Mp (M ) Cu, Ni) centers of
these models and compare the spectral data of the reduced
CO-adducts with that of the Ared-CO (S ) 1/2) signal of the
enzyme in order to establish the mode of CO binding by the
A-cluster of ACS/CODH.
Experimental Section
Thiosalicylic acid, 1,2-phenylenediamine, 1,8-diaminonaphtha-
lene, triethylamine, [Ni(dppe)Cl2], CuCl, [Cu(MeCN)4]PF6, 2,9-
dimethyl-1,10-phenanthroline (neocuproine, abbreviated as neo),
2,2′:6′,2′′-terpyridine (terpy), 1,2-ethanedithiol (edt), and 1,10-
phenanthroline (phen) were purchased from Aldrich Chemical Co.
and used without further purification. NpPepSH4 (N,N′-naphthale-
nebis(o-mercaptobenzamide),26 2,2′-dithiosalicyl chloride,26 (Et4N)2-
[Ni(NpPepS)]26 (1), (Et4N)2[NiCl4],28 [Cu(neo)Cl],29a (Na)3[Cu3-
(edt)3],29b and [Ni(terpy)Cl2]30 were synthesized by following
published procedures. All manipulations were carried out under N2
(where needed) using Schlenk lines or drybox techniques. The
solvents were purified by standard techniques and distilled prior
to use.
(17) (a) Harrop, T. C.; Mascharak, P. K. Acc. Chem. Res. 2004, 37, 253-
260. (b) Mascharak, P. K. Coord. Chem. ReV. 2002, 225, 201-214.
(c) Nagashima, S.; Nakasako, M.; Dohmae, N.; Tsujimura, M.; Takio,
K.; Odaka, M.; Yohda, M.; Kamiya, N.; Endo, I. Nat. Struct. Biol.
1998, 5, 347-351. (d) Huang, W.; Jia, J.; Cummings, J.; Nelson, M.;
Schneider, G.; Lindqvist, Y. Structure 1997, 5, 691-699.
(18) (a) Barondeau, D. P.; Kassmann, C. J.; Bruns, C. K.; Tainer, J. A.;
Getzoff, E. D. Biochemistry 2004, 43, 8038-8047. (b) Wuerges, J.;
Lee, J.-W.; Yim, Y.-I.; Yim, H.-S.; Kang, S.-O.; Carugo, K. D. Proc.
Natl. Acad. Sci. U.S.A. 2004, 101, 8569-8574.
Synthesis of Compounds. PhPepSH4 (N,N′-Phenylenebis(o-
mercaptobenzamide). The synthesis of the ligand comprises the
following steps.
(19) Rao, P. V.; Bhaduri, S.; Jiang, J.; Holm, R. H. Inorg. Chem. 2004,
43, 5833-5849.
(20) (a) Krishnan, R.; Riordan, C. G. J. Am. Chem. Soc. 2004, 126, 4484-
4485. (b) Krishnan, R.; Voo, J. K.; Riordan, C. G.; Zahkarov, L.;
Rheingold, A. L. J. Am. Chem. Soc. 2003, 125, 4422-4423.
(21) Hatlevik, Ø.; Blanksma, M. C.; Mathrubootham, V.; Arif, A. M.; Hegg,
E. L. J. Biol. Inorg. Chem. 2004, 9, 238-246.
(26) Harrop, T. C.; Olmstead, M. M.; Mascharak, P. K. Inorg. Chim. Acta
2002, 338, 189-195.
(27) (a) Harrop, T. C.; Olmstead, M. M.; Mascharak, P. K. J. Am. Chem.
Soc. 2004, 126, 14714-14715. (b) Harrop, T. C.; Olmstead, M. M.;
Mascharak, P. K. Chem. Commun. 2004, 1744-1745.
(22) Wang, Q.; Blake, A. J.; Davies, E. S.; McInnes, E. J. L.; Wilson, C.;
Schro¨der, M. Chem. Commun. 2003, 3012-3013.
(28) Gill, N. S.; Taylor, F. B. Inorg. Synth. 1967, 9, 136-143.
(29) (a) Healy, P. C.; Pakawatchai, C.; White, A. H. J. Chem. Soc., Dalton
Trans. 1985, 2531-2539. (b) Rao, C. P.; Dorfman, J. R.; Holm, R.
H. Inorg. Chem. 1986, 25, 428-439. (c) Anderson, O. P.; Brito, K.
K.; Laird, S. K. Acta Cryst. 1990, C46, 1600-1603.
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A. J. Inorg. Nucl. Chem. 1967, 29, 1711-1716.
(23) Golden, M. L.; Rampersad, M. V.; Reibenspies, J. H.; Darensbourg,
M. Y. Chem. Commun. 2003, 1824-1825.
(24) Linck, R. C.; Spahn, C. W.; Rauchfuss, T. B.; Wilson, S. R. J. Am.
Chem. Soc. 2003, 125, 8700-8701.
(25) Harrop, T. C.; Mascharak, P. K. Coord. Chem. ReV. 2005, 249, 3007-
3024.
3426 Inorganic Chemistry, Vol. 45, No. 8, 2006

Analogues of the ActiWe Site of the A-Cluster of ACS/CODH
Step 1. (PhPepS-)2. A solution of 1,2-phenylenediamine (0.23
g, 2.13 mmol) and triethylamine (0.67 g, 6.63 mmol) dissolved in
10 mL of CH2Cl2 was quickly added to a solution of 2,2′-
dithiosalicyl chloride (0.72 g, 2.10 mmol) in 10 mL of CH2Cl2.
The resulting pale yellow-brown solution was stirred for 48 h at
room temperature. This solution was then washed with aqueous
NaHCO3 and NaCl. The CH2Cl2 layer was dried with MgSO4 and
filtered, and the solvent was removed by rotary evaporation to yield
an oily yellow residue. The oil was triturated three times with Et2O
was then stirred at room temperature for 2 h. Next, the solvent
was removed via short-path vacuum distillation and the red oily
residue was triturated with 20 mL of degassed MeCN/Et2O (1:1)
mixture. The red solid thus obtained was collected by filtration,
washed with cold Et2O, and dried on a high-vacuum line for 1 h.
Yield: 0.086 g (66%). Anal. calcd for C42H44N5O2S2CuNi (4): C,
60.25; H, 5.30; N, 8.37; found: 60.34; H, 5.23; N, 8.39. Selected
IR bands (KBr plates, cm-1): 1524 (vs, νco). Absorption spectrum
in MeCN, λmax nm (ꢀ, M-1 cm-1): 495 (2 940), 363 sh (10 650),
312 sh (19 600). 1H NMR (298 K, CD3CN, 500 MHz): (ppm from
TMS) 8.40 (d, 1H), 8.11 (s, 1H), 7.94 (d, 1H), 7.84 (d, 1H), 7.67
(t, 1H), 6.75 (t, 1H), 6.62 (t, 1H), 6.50 (d, 1H), 6.31 (t, 1H), 3.34
(s, 3H), 3.12 (q, 4H), 1.17 (t, 6H).
(Et4N)2[Ni{Ni(NpPepS)}2] (5). A batch of 0.027 g of (Et4N)2-
[NiCl4] (0.059 mmol) dissolved in 2 mL MeCN was added to a
solution containing 0.087 g (0.117 mmol) of 1 in 10 mL of degassed
MeCN. The initial red-orange color of the solution turned pale
orange, and a dark red microcrystalline precipitate appeared within
minutes. This heterogeneous solution was stirred for 1 h, and then
the mixture was filtered. The microcrystalline dark solid was
collected, washed with dry Et2O, and dried in vacuo. Yield: 0.065
g (85%). Anal. calcd for C64H68N6O4S4Ni3 (5): C, 59.61; H, 5.31;
N, 6.52; found: 59.70; H, 5.27; N, 6.51. Selected IR bands (KBr
plates, cm-1): 1538 (vs, νco).
1
(10 mL) to afford a pale yellow solid. Yield: 0.32 g (41%). H
NMR (298 K, CDCl3, 500 MHz): (ppm from TMS) 8.59 (s, 1H,
NH), 7.67 (d, 1H), 7.53 (t, 1H), 7.39 (m, 2H), 7.21 (m, 2H). Selected
IR bands (KBr matrix, cm-1): 3217 (m, νNH), 1652 (vs, νco).
Step 2. PhPepSH4. To a degassed THF solution (10 mL) of
(PhPepS-)2 (0.32 g, 0.85 mmol) was slowly added solid NaBH4
(0.17 g, 4.49 mmol) in small portions at 4 °C. The bright yellow-
orange solution was then allowed to stir at room temperature for
16 h. Next, the THF solution was concentrated to ∼10% of the
original volume via short-path vacuum distillation and 6 M acetic
acid was added dropwise at 4 °C until the pH was 3. The light
cream-colored solid that precipitated almost immediately upon
addition of acid was collected by filtration, washed with degassed
water, and dried on a high-vacuum line for 2 h. Yield: 0.30 g
1
(90%). H NMR (298 K, CDCl3, 500 MHz): (ppm from TMS)
8.73 (s, 1H, NH), 7.69 (d, 1H), 7.56 (t, 1H), 7.36 (d, 1H), 7.31 (t,
1H), 7.22 (m, 2H), 4.53 (br s, 1H, SH). Selected IR bands (KBr
plates, cm-1): 3300 (m, νNH), 2552 (w, νSH), 1652 (vs, νco).
(Et4N)2[Ni(PhPepS)] (2). A batch of NaH (0.054 g, 2.24 mmol)
was added to a solution of PhPepSH4 (0.17 g, 0.45 mmol) in 10
mL of degassed DMF, and the pale yellow-brown solution was
allowed to mix for ∼20 min to ensure that all NaH had reacted.
To this solution was then added a batch of (Et4N)2[NiCl4] (0.21 g,
0.44 mmol) dissolved in 2 mL of DMF. The dark red-brown
solution thus obtained was stirred for 4 h at room temperature. Next,
DMF was removed via short-path vacuum distillation and the
residue was dissolved in 25 mL of MeCN and filtered. The resulting
red solution was concentrated to ∼50% of the original volume,
and the desired product was isolated as a red microcrystalline solid.
Yield: 0.25 g (82%). Anal. calcd for C36H52N4O2S2Ni (2): C, 62.16;
H, 7.53; N, 8.05; found: 62.11; H, 7.61; N, 8.02. Selected IR bands
(KBr plates, cm-1): 1521 (vs, νco). Electronic absorption spectrum
in MeCN, λmax nm (ꢀ, M-1 cm-1): 545 (sh 610), 384 (8 845), 331
(19 510).1H NMR (298 K, CD3CN, 500 MHz): (ppm from TMS)
8.06 (d, 1H), 7.95 (d, 1H), 7.22 (d, 1H), 6.78 (m, 2H), 6.51 (t,
1H), 3.14 (q, 8H), 1.11 (t, 12H).
(Et4N)2[Ni(DMF)2{Ni(NpPepS)}2] (6). A batch of 0.053 g (0.04
mmol) of 5 was allowed to stir for 2 h at room temperature in 10
mL of degassed DMF. The initial heterogeneous solution slowly
became homogeneous and turned bright red in color. The DMF
was removed via vacuum distillation, and the resulting oily red
material was triturated with 10 mL of dry Et2O to obtain the desired
product as a fine red solid. Yield: 0.053 g (94%). Anal. calcd for
C70H82N8O6S4Ni3 (6): C, 58.56; H, 5.76; N, 7.80; found: 58.64;
H, 5.73; N, 7.79. Selected IR bands (KBr plates, cm-1): 1645 (s,
νco DMF), 1532 (vs, νco). Absorption spectrum in DMF, λmax nm
(ꢀ, M-1 cm-1): 525 (sh), 437 (12 410).
(Et4N)2[Ni{Ni(PhPepS)}2] (7). A solution of 0.035 g of (Et4N)2-
[NiCl4] (0.075 mmol) dissolved in 3 mL of MeCN was added to a
red-orange solution of 0.102 g (0.147 mmol) of 2 in 20 mL of
degassed MeCN. The color of the reaction mixture rapidly turned
to dark red. The deep red solution was stirred for 1 h at room
temperature, and then its volume was reduced to half by short-
path vacuum distillation. Storage of this solution at -20 °C for 16
h resulted in the precipitation of a red crystalline solid. This
microcrystalline red solid was collected, washed with dry Et2O,
and dried in vacuo. Yield: 0.080 g (92%). Anal. calcd for
C56H64N6O4S4Ni3 (7): C, 56.55; H, 5.42; N, 7.07; found: 56.64;
H, 5.37; N, 7.10. Selected IR bands (KBr plates, cm-1): 3052 (w),
2983 (w), 1591 (s), 1566 (s), 1538 (vs, νco), 1467 (s), 1442 (s),
1393 (w), 1345 (s), 1295 (w), 1268 (m), 1220 (w), 1182 (w), 1172
(w), 1140 (w), 1118 (w), 1059 (w), 1040 (w), 1002 (w), 956 (w),
791 (w), 755 (m), 691 (w), 601 (w), 515 (w). Absorption spectrum
in MeCN, λmax nm (ꢀ, M-1 cm-1): 850 sh (800), 660 (2500), 560
sh (3030), 470 (3850). 1H NMR (298 K, CD3CN, 500 MHz): (ppm
from TMS) 8.07 (d, 1H), 7.95 (d, 1H), 7.21 (d, 1H), 6.78. (m, 2H),
6.50 (t, 1H), 3.14 (q, 4H), 1.13 (t, 6H).
(Et4N)[Cu(neo)Ni(NpPepS)] (3). A batch of 0.04 g (0.14 mmol)
of [Cu(neo)Cl] was added to a red-orange solution of 0.10 g (0.14
mmol) of 1 in 10 mL of DMF. The burgundy-red homogeneous
solution thus obtained was stirred for 12 h at room temperature.
Next, DMF was removed in vacuo and 10 mL of MeCN was added
to the residue. The pale red solution with a dark precipitate was
filtered, and the dark red solid was washed with 10 mL of MeCN
and dried in vacuo. Yield: 0.087 g (71%). Anal. calcd for
C46H46N5O2S2CuNi (3): C, 62.27; H, 5.23; N, 7.89; found: 62.14;
H, 5.31; N, 7.92. Selected IR bands (KBr plates, cm-1): 1516 (vs,
νco). Absorption spectrum in MeCN, λmax nm (ꢀ, M-1 cm-1): 495
(Et4N)2[Ni(DMF)2{Ni(PhPepS)}2] (8). A batch of 0.027 g
(0.022 mmol) of 7 was allowed to stir for 2 h at room temperature
in 5 mL of degassed DMF. Next, the solvent was removed via
vacuum distillation and the resulting oily red material was triturated
with 5 mL of dry Et2O to obtain the desired product as a fine red
solid. Yield: 0.028 g (97%). Anal. calcd for C62H78N8O6S4Ni3 (8):
C, 55.75; H, 5.89; N, 8.39; found: 55.74; H, 5.83; N, 8.41. Selected
IR bands (KBr plates, cm-1): 1646 (vs, νco DMF), 1538 (vs, νco).
1
(12 250), 420 (12 130), 326 (32 000). H NMR (298 K, CD3CN,
500 MHz): (ppm from TMS) 8.43 (d, 1H), 7.96 (s, 1H), 7.93 (d,
1H), 7.68 (d, 1H), 7.50 (t, 2H), 7.17 (t, 1H), 6.93 (t, 1H), 6.50 (d,
1H), 6.43 (t, 1H), 3.11 (q, 4H), 2.74 (s, 3H), 1.16 (t, 6H).
(Et4N)[Cu(neo)Ni(PhPepS)] (4). A batch of 0.05 g (0.16 mmol)
of [Cu(neo)Cl] was slowly added to a solution of 0.11 g (0.15
mmol) of 2 in 15 mL of MeCN. The deep burgundy-red solution
Inorganic Chemistry, Vol. 45, No. 8, 2006 3427

Harrop et al.
Absorption spectrum in DMF, λmax nm (ꢀ, M-1 cm-1): 527 (1080),
380 sh (15 300), 335 (38 130).
for 6‚3DMF were collected at 130 K on a Siemens P4 system. Cu
KR (1.54178 Å) radiation was used, and the data were corrected
for absorption. The structures were solved using the standard
SHELXS-97 package. Machine parameters, crystal data, and data
collection parameters for all the complexes are summarized in Table
S1, while selected bond distances and angles are reported in Table
S2. Both these tables have been submitted as Supporting Informa-
tion along with other crystallographic data for all of the complexes.
[Ni(terpy)Ni(NpPepS)] (9). A slurry of 0.048 g (0.13 mmol) of
[Ni(terpy)Cl2] in 1 mL of MeCN was added to a solution containing
0.100 g (0.13 mmol) of 1 in 10 mL MeCN. Within 5 min, the
initial red-orange solution turned pale and a red-brown precipitate
appeared. The precipitate was filtered, washed with cold MeCN,
and dried in vacuo. Yield: 0.076 g (75%). Anal. calcd for
C39H25N5O2S2Ni2 (9): C, 60.27; H, 3.24; N, 9.01; found: 60.21;
H, 3.30; N, 8.97. Selected IR bands (KBr plates, cm-1): 3051 (w),
1585 (s), 1568 (s), 1531 (vs, νco), 1474 (m), 1451 (m), 1429 (w),
1385 (s), 1355 (m), 1321 (w), 1265 (w), 1248 (w), 1184 (w), 1163
(w), 1112 (w), 1095 (w), 1054 (w), 1035 (w), 1016 (w), 958 (w),
820 (w), 771 (m), 742 (m), 680 (w), 650 (w), 642 (w), 619 (w),
592 (w). Absorption spectrum in DMF, λmax nm (ꢀ, M-1 cm-1):
450 sh (8500), 427 (10 200), 337 (34 680).
Results and Discussion
Synthesis. The Nid mimics 126 and 227a served as the
metallosynthons in the construction of the higher-nuclearity
analogues reported in this account. To date, several Ni(II)-
dicarboxamido-dithiolato complexes have been reported in
the literature.19,21,31-33 The synthetic route that we have
followed to obtain the Ni(II) complexes 1 and 2 was
originally developed in this laboratory for the synthesis of
Fe(III)-carboxamide complexes.34 Reactions of (Et4N)2-
[NiCl4] with the deprotonated (with the aid of NaH) ligands
NpPepS4- or PhPepS4- in solvents such as DMF readily
afford complexes 1 and 2 in high yields. These Ni(II)
complexes with N2S2 chromophores are inherently stable in
the solid state.
Failures in the initial attempts to synthesize Ni-Cu
dinuclear model complexes in the present work provide some
synthetic tips for isolation of such systems. Addition of
simple Cu(I) salts such as CuCl or [Cu(MeCN)4]PF6 to DMF
solutions of the Nid mimic 1 invariably results in the
formation of the trinuclear species (Et4N)[Cu{Ni(NpPepS)}2]
regardless of the choice of solvent, Cu(I) salt, or reagent
stoichiometry.27b This observation suggests that, in order to
synthesize discrete dinuclear species, one must employ Cu-
(I) starting complexes with less-labile ligands. Use of the
trinuclear Cu(I) complex [Cu3(edt)3]3- (edt ) 1,2-ethane-
dithiol),29b however, leads to no reaction with 1 or 2 in
solvents such as DMF, MeCN, or MeOH at room temper-
ature. When reaction mixtures with 1 is heated to 65 °C in
DMF for 24 h, one obtains the trinuclear complex (Et4N)-
[Cu{Ni(NpPepS)}2] instead of the desired S-bridged Ni-
Cu complex [Cu(edt)Ni(NpPepS)]3-. In contrast, when one
employs [Cu(neo)(Cl)]29a as the starting Cu(I) complex, the
reaction indeed takes the desired course. For instance,
reaction of [Cu(neo)Cl] with 1 or 2 in MeCN at room
temperature cleanly affords the Ni-Cu dinuclear complexes
3 and 4, respectively, in high yields. Clearly, the strong
preference of the neo ligand for Cu(I) center, as well as the
tetrahedral geometric preference of Cu(I), allows for the
formation of 3 and 4. Complexes 3 and 4 are also obtained
when [Cu(neo)(SR)] (R ) C6H5, p-C6H4-Cl)29c are used as
the starting Cu(I) complexes. In the solid state, 3 and 4 are
stable for months and no oxidation of the Cu(I) center is
observed (as verified by 1H NMR and electronic absorption
spectroscopy).
[Ni(dppe)Ni(PhPepS)] (10). A batch of 0.154 g (0.292 mmol)
of [Ni(dppe)Cl2] was slowly added to a solution of 0.204 g (0.293
mmol) of 2 in 10 mL of MeCN. Almost immediately, the red-
brown solution turned pale and a blue-green microcrystalline solid
appeared in the reaction mixture. The solid was filtered, washed
with cold MeCN, and dried in vacuo. Yield: 0.223 g (85%). Anal.
calcd for C46H46N5O2S2CuNi (10): C, 61.92; H, 4.07; N, 3.14;
found: 62.03; H, 4.16; N, 3.12. Selected IR bands (KBr plates,
cm-1): 1538 (vs, νco). Electronic absorption spectrum in CH2Cl2,
λmax nm (ꢀ, M-1 cm-1): 594 (3 040), 506 (sh 1 890), 345 (21
910).1H NMR (298 K, CDCl3, 500 MHz): (ppm from TMS) 8.03
(m, 2H), 7.90 (s, 2H), 7.61 (s, 5H), 7.39 (s, 1H), 7.31 (s, 2H), 6.96
(t, 1H), 6.74 (t, 1H), 6.51 (t, 1H), 6.43 (d, 1H), 1.87 (t, 2H).
Physical Measurements. Electronic absorption spectra were
recorded on a Perkin-Elmer Lambda 9 UV/vis/NIR spectropho-
tometer. A Perkin-Elmer Spectrum One or Nicolet Nexus 870 FTIR
1
was used to monitor the infrared spectra. The H NMR spectra
were recorded at 298 K on a Varian Unity Plus 500 MHz
spectrometer. EPR spectra were collected on a Bruker EleXsys E500
spectrometer at X-band frequencies at liquid-N2 temperature. A
Johnson-Matthey magnetic susceptibility balance was used to
determine the room-temperature magnetic susceptibility values of
the solid complexes. Electrochemical measurements were performed
with Princeton Applied Research instrumentation (model 273A) at
298 K in DMF or CH2Cl2 using either 0.1 M (Et4N)(ClO4) or
(nBu4N)(PF6) as the supporting electrolyte. The working electrode
was a Beckman Pt-inlay working electrode, and the potentials were
measured versus a SCE.
X-ray Data Collection and Structure Solution and Refine-
ment. Red needles of 2 were grown by slow diffusion of Et2O
into a dilute solution of 2 in MeCN at 4 °C. Red plates of 3‚0.5Et2O‚
0.5H2O were obtained from slow diffusion of Et2O into a saturated
solution of 3 in MeCN/DMF (1:1). Red needles of 4‚H2O were
obtained upon slow cooling of an MeCN/Et2O (1:1) solution of
the complex at -20 °C. Black blocks of 5‚DMF were obtained by
slow diffusion of Et2O into a saturated solution of the complex in
MeCN/DMF (9:1). Red parallelepipeds of 6‚3DMF were grown
by diffusion of Et2O into a dilute solution of the complex in DMF.
Red blocks of 8 were grown by slow diffusion of Et2O into a dilute
solution of the complex in DMF. Black prisms of 10‚CH2Cl2 were
obtained from slow evaporation of a concentrated solution of 10
in a CH2Cl2/toluene (3:1) mixture at room temperature. Diffraction
data for 2, 4‚H2O, and 10‚CH2Cl2 were collected at 91 K on a
Bruker APEX system. Diffraction data for 3‚0.5Et2O‚0.5H2O, 5‚
DMF, and 8 were collected at 91 K on a Bruker SMART 1000
system. For these structures, Mo KR (0.71073 Å) radiation was
used and the data were corrected for absorption. Diffraction data
(31) (a) Kru¨ger, H.-J.; Peng, G.; Holm, R. H. Inorg. Chem. 1991, 30, 734-
742. (b) Kru¨ger, H.-J.; Holm, R. H. Inorg. Chem. 1987, 26, 3645-
3647.
(32) Dutton, J. C.; Fallon, G. D.; Murray, K. S. Chem. Lett. 1990, 983-
986.
(33) Hanss, J.; Kru¨ger, H.-J. Angew. Chem., Int. Ed. 1998, 37, 360-363.
(34) Marlin, D. S.; Mascharak, P. K. Chem. Soc. ReV. 2000, 29, 69-74.
3428 Inorganic Chemistry, Vol. 45, No. 8, 2006

Analogues of the ActiWe Site of the A-Cluster of ACS/CODH
Similar reactivity has also been noted in our attempts to
synthesize dinuclear Ni(II) species. Reactions of Ni(II) salts
such as (Et4N)2[NiCl4] with 1 or 2 in MeCN afford the
corresponding trinuclear complexes 5 and 7 in high yield.
These trinuclear complexes form regardless of the Ni(II) salt/
metallosynthon stoichiometry. Isolation of these complexes
is aided by the high insolubility of 5 and 7 in MeCN; the
trinuclear complexes precipitate out of solution within
minutes. Interestingly, dissolution of 5 and 7 in DMF (a slow
process) results in coordination of two molecules of DMF
to the central Ni(II) ion (designated as NiC) affording the
DMF adducts 6 and 8, respectively. This binding is also
reversible. When the DMF adducts 6 and 8 are treated with
solvents such as MeCN or THF, the respective trinuclear
species 5 and 7 form almost immediately (verified by IR
Figure 3. ORTEP diagram of the anion [Ni(PhPepS)]2- (anion of 2) (50%
probability) with the atom-labeling scheme. H atoms are omitted for the
sake of clarity.
1
and H NMR).
to the presence of the carboxamido nitrogens in 2. The angles
at the Ni(II) center are slightly distorted from the ideal 90°
value due to the short bite of the phenylenediamido portion
of the ligand frame (N1-Ni-N2 ) 85.52(11)°). The average
Ni-Namido bond length (1.907(3) Å) compares well with other
Ni(II)-carboxamido complexes.21,26,31-33,36 The average Ni-S
bond distance (2.158(10) Å) is also within the range of Ni-S
distances found in analogous Ni(II)-dicarboxamido-dithi-
olato species.21,26,31-33
The dinuclear Ni-Ni model complexes have been syn-
thesized by following the strategy used to isolate the Ni-
Cu complexes 3 and 4. Reaction of 1 equiv of [Ni(terpy)Cl2]
(terpy ) 2,2′:6′,2′′-terpyridine) with 1 in MeCN affords 9,
a Ni-Ni dimer in which the modeled Nip site is five-
coordinate. The isolation of 9 is aided by its lack of solubility
in a variety of polar solvents such as MeOH and MeCN due
to the overall neutral charge of the complex. Since the as-
isolated Nip site of ACS is four-coordinate in the crystal
structure, we employed a second Nip synthon, [Ni(dppe)-
Cl2] (dppe ) 1,2-bis(diphenylphosphino)ethane), in such
reaction. This Nip synthon is expected to favor an easier
reduction to the Ni(I) oxidation state and further facilitate
binding of CO. However, all attempts to synthesize a Ni-
Ni dimer with 1 and [Ni(dppe)Cl2] led to the formation of
the trinuclear species 5. In contrast, reaction of 2 with 1 equiv
of [Ni(dppe)Cl2] in MeCN affords 10 as a blue-green
microcrystalline solid in 85% yield. Steric interactions
between the folded structure of the {Ni(NpPepS)} moiety26
and the dppe ligand frame presumably prevent the formation
of the dinuclear complex in the first case, while the more
rigid ligand frame of 2 allows formation of the desired dimer
10 without such hindrance. It is therefore evident that proper
design of the ligand frame of the Nid metallosynthon is
crucial for the successful isolation of Nip-Nid ACS models.
Structure and Properties. (Et4N)2[Ni(PhPepS)] (2). The
structure of [Ni(PhPepS)]2- (anion of 2) is shown in Figure
3. The coordination geometry around nickel is square planar
arising from two carboxamido nitrogens and two thiolato
sulfurs in cis geometry. Although the overall disposition of
the PhPepS4- ligand frame is similar to that of NpPepS4- in
1,26 there are some noted differences. For example, the extent
of the ‘butterfly’ folding of the aryl sulfur rings observed in
1 is not as extreme in the case of 2. This is reflected in the
more rigid five-member chelate ring of the phenylenediamido
portion of 2 (nearly coplanar with the NiN2S2 plane)
compared to the six-member chelate ring of the naphtha-
lenediamido portion of 1 (almost perpendicular to the NiN2S2
plane). Interestingly, [Ni(tsalphen)], an analogous Ni(II)
complex derived from a ligand frame similar to 2 but with
imine nitrogen coordination, is completely planar.35 This
suggests that the bending of the aryl rings is most likely due
Coordination of deprotonated carboxamido nitrogen to
metal centers is readily indicated by the red-shift of the
carbonyl stretching frequency (νco) of the complex with
respect to the νco of the free ligand.34 Complex 2 exhibits its
ν
co at 1521 cm-1 compared to 1652 cm-1 for the free ligand
PhPepSH4. In MeCN, 2 exhibits a dark red color arising from
strong ligand-to-metal charge-transfer absorption at 384 nm
and a d-d band at 545 nm typical for Ni(II) complexes with
dicarboxamido-dithiolato (N2S2) coordination.21,26,31-33 The
1
clean H NMR spectrum of 2 in CD3CN confirms that the
square-planar geometry of 2 is retained in solution. Ligation
of deprotonated carboxamido nitrogen to nickel in general
provides exceptional stability to the 2+ and 3+ oxidation
states.21,31-33 In DMF, 2 displays an irreversible metal-
centered oxidation wave at 0.22 V (vs SCE). This value is
more positive than the oxidation potential of other Ni(II)-
N2S2 complexes possibly due to the weaker donor strength
of the aryl thiolate donors in 2 compared to the alkanethi-
olates present in analogous complexes. Not surprisingly, 2
exhibits no reduction wave down to a potential of -1.8 V
(vs SCE, DMF) due to the presence of strong σ-donors
(carboxamido-N and thiolato-S) around the Ni(II) center.
(Et4N)[Cu(neo)Ni(NpPepS)] (3). The structure of 3
consists of a square-planar Ni(II) ion bridged to a distorted
tetrahedral Cu(I) center via the thiolato-S donors of the
NpPepS4- ligand frame (Figure 4). Close scrutiny of the Ni-
Namido and Ni-S bond distances in 3 (av ) 1.899(4) and
2.1950(15) Å, respectively) reveals little changes from those
noted for the Ni(II) monomer 1. The Cu‚‚‚Ni distance of 3
(3.074 Å) is somewhat longer than that of the Cu form of
ACS/CODH (2.792 Å).5 Steric constraints imposed by the
(35) Smeets, W. J. J.; Spek, A. L.; Henderson, R. K.; Bouwman, E.; Reedijk,
J. Acta Crystallogr., Sect. C 1997, C53, 1564-1566.
Inorganic Chemistry, Vol. 45, No. 8, 2006 3429

Harrop et al.
Figure 4. ORTEP diagram of [Cu(neo)Ni(NpPepS)]- (anion of 3) (50%
probability) with the atom-labeling scheme. H atoms are omitted for the
sake of clarity.
Figure 5. ORTEP diagram of [Cu(neo)Ni(PhPepS)]- (anion of 4) (50%
probability) with the atom-labeling scheme. H atoms are omitted for the
sake of clarity.
NpPepS4- ligand frame are presumably responsible for the
longer metal-metal distance compared with the enzyme
value. The average Cu-N distance in 3 (2.047(4) Å) is
typical of Cu(I)-neocuproine-type complexes.37 However,
the two Cu-S distances are quite different with Cu-S1 )
2.2670(16) and Cu-S2 ) 2.3198(16) Å. The distorted
arrangement of the donor atoms around the Cu(I) center is
further supported in the large deviation of the bond angles
(N3-Cu-N4 ) 82.66(18)° and N3-Cu-S1 ) 129.79(14)°)
from the ideal tetrahedral value of 109.5°. Similar distortion
has also been observed in other sulfur-bridged Ni(II)-Cu-
(I) complexes.25,27b
Figure 6. ORTEP diagram of [Ni{Ni(NpPepS)}2]2- (anion of 5) (50%
probability) with the atom-labeling scheme. H atoms are omitted for the
sake of clarity.
Metalation of the sulfur ligands of the {Ni(NpPepS)}
moiety in 3 is readily indicated by the blue-shift of the νco
value of the complex (1516 cm-1 compared to 1510 cm-1
in monomeric 1). Enhanced charge donation by the carboxa-
mido-N to compensate for the decreased donor strength of
sulfur (following metalation by Cu) is presumably respon-
sible for this blue-shift. Complex 3 is diamagnetic and
exhibits a clean 1H NMR spectrum. Although metalation of
thiolate-S donors can alter the charge density at the Ni(II)
of the C1-S1-Ni angle which is more compressed in 4
(99.06(5)°) than in 2 (106.53(11)°) and the highly distorted
tetrahedral geometry about the Cu(I) center. For example,
there is a significant difference in the two Cu-N bond
lengths (Cu-N3 ) 2.0194(14) Å; Cu-N4 ) 2.0894(14) Å),
the two Cu-S distances (Cu-S1 ) 2.2496(4) Å; Cu-S2 )
2.3508(4) Å), and the bond angles range from 82.08(5)°
(N3-Cu-N4) to 140.13(4)° (N3-Cu-S1). As a result, the
Cu‚‚‚Ni bond distance of 4 (3.1435(2) Å) is longer than that
observed in Cu-ACS. Like 3, complex 4 exhibits a clean
diamagnetic 1H NMR spectrum and exhibits no Ni(II)/Ni(I)
reduction wave in its cyclic voltammogram.
(Et4N)2[Ni{Ni(NpPepS)}2] (5). An ORTEP drawing of
the anion of the trinuclear Ni(II) complex 5 is shown in
Figure 6. The two terminal Ni(II) centers (designated as NiT;
Ni1 and Ni3 in Figure 5) and the central Ni(II) center
(designated as NiC; Ni2 in Figure 5) of 5 all lie in one
extended plane in a slant chair configuration resulting from
the orientation of the naphthalene rings. The two aryl sulfur
rings of the NpPepS4- ligand frame fold in an up-down
sequence and appear as railings for the N2NiTS2-NiC-S2-
NiTN2 platform. The NiT-Namido and NiT-S bond distances
in 5 (av ) 1.880(3) and 2.1769 Å, respectively) are similar
to those observed in 1, while the average NiC-S bond length
(2.2368(10) Å) is slightly longer than those distances
observed in similar Ni(II) trinuclear species.21,38 Unique
center making the Ni(I) oxidation state more accessible,23
3
does not exhibit any observable redox wave down to -1.8
V (vs SCE, DMF). Clearly, the Ni(I) state is not supported
in this complex eVen with sulfur metalation. This lends further
support toward a nonredox role for the Nid site in the enzyme.
(Et4N)[Cu(neo)Ni(PhPepS)] (4). The structure of the
anion of the dinuclear Ni(II)-Cu(I) complex 4 is shown in
Figure 5. Much like 3, this complex also consists of a square-
planar Ni(II) ion sulfur-bridged to a distorted tetrahedral Cu-
(I) center. The metric parameters of the NiN2S2 portion of 4
(av Ni-Namido ) 1.9037(11) Å) are similar to that of
monomer 2 except for slight elongation of the Ni-S bond
distance (av ) 2.1872(4) Å). Also, the bending of the aryl
thiolate rings away from the NiN2S2 coordination plane is
more noticeable in 4 compared to 2 as a result of the steric
clash between the methyl groups of the neocuproine unit with
the PhPepS4- ligand frame. This is reflected in the change
(36) Chapman, R. L.; Vagg, R. S. Inorg. Chim. Acta 1979, 33, 227-234.
(37) Pallenberg, A. J.; Koenig, K. S.; Barnhart, D. M. Inorg. Chem. 1995,
34, 2833-2840.
3430 Inorganic Chemistry, Vol. 45, No. 8, 2006

Analogues of the ActiWe Site of the A-Cluster of ACS/CODH
Figure 8. ORTEP diagram of [Ni(DMF)2{Ni(PhPepS)}2]2- (anion of 8)
(50% probability) with the atom-labeling scheme. H atoms are omitted for
the sake of clarity.
Figure 7. ORTEP diagram of [Ni(DMF)2{Ni(NpPepS)}2]2- (anion of 6)
(50% probability) with the atom-labeling scheme. H atoms are omitted for
the sake of clarity.
tion in 6 (3.374 Å) compared to 5 (3.2269(7) Å). The bending
of the aryl sulfur rings of the NiTN2S2 units in 6 is also less
pronounced (C1-S1-Ni1 ) 97.67(14)° compared to 87.72-
(13)° in 5). A small trans influence of the coordinated DMF
molecules in 6 is reflected in the two longer NiC-S bond
distances (Ni2-S1 ) 2.4877(13) Å; Ni2-S3 ) 2.4495(12)
Å). The increase in NiC-S could also arise from the increased
metal-ligand electron repulsion in going from low-spin
planar 5 (S ) 0) to high-spin octahedral 6 (S ) 1).
folding of the NpPepS4- ligand around the NiT centers in 5
is presumably responsible for this lengthening of the NiC-S
bonds. Further comparison of the structural parameters of 5
with those of 1 reveal several differences in the coordination
structure and ligand folding about the Ni(II) centers. For
example, in 5, the S1-Ni1-S2 bite angle is more com-
pressed (86.85(4)°) compared to 1 (91.91(10)°) as a result
of NiC coordination. Most notably, the ‘butterfly’ folding of
the aryl sulfur rings in 5 allow the two adjacent rings on
each NpPepS4- ligand frame to become much closer to each
other compared to 1. Finally, the C1-S1-Ni1 bond angle
is considerably more closed in 5 (87.72(13)°) than in 1
(101.2(2)°).
Complex 6 exhibits an additional νco stretch at 1645 cm-1
due to the O-coordinated DMF molecules at the NiC center.
The S ) 1 spin state of 6 has been confirmed by measure-
ment of the magnetic moment of the complex in the
polycrystalline state (µeff ) 2.87 µB at 298 K).
The extremely low solubility of 5 in CD3OD, CD3CN, and
(Et4N)2[Ni{Ni(PhPepS)}2] (7). So far, we have not been
able to grow good quality crystals of this complex for
diffraction studies. However, microanalytical and spectro-
scopic data confirm an extended planar structure similar to
that of complex 5. This diamagnetic complex is more soluble
in a variety of solvents than its analogue 5, and its clean 1H
NMR spectrum in CD3CN is consistent with square-planar
coordination around the three Ni(II) centers. The electronic
absorption spectrum of 7 consists of several peaks in the
400-500 nm range arising from multiple ligand-to-metal
charge transfer (LMCT) bands arising from the NiS4 and
NiN2S2 chromophores. As expected, the νco band of 7 is
shifted to higher energy (1538 cm-1) compared to the
monomeric complex 2 (1521 cm-1).
(Et4N)2[Ni(DMF)2{Ni(PhPepS)}2] (8). The structure of
the anion of the trinuclear complex 8 is shown in Figure 8.
Much like the analogous trimer 6, complex 8 also comprises
two NiTN2S2 units coordinated to an octahedral NiC center
(Ni2 in Figure 8). However, the NiTN2S2 moieties prefer to
stay coplanar due to the decreased steric demands of the
PhPepS4- ligand frame in 8. This results in coordination of
the two DMF molecules in a trans position at the NiC center.
The average NiC-S and NiC-O bond distances of 8 (2.4475-
(16) and 2.063(5) Å, respectively) are very similar to those
observed in 6 and other related complexes. When compared
with 2, the overall folding and metric parameters of the
PhPepS4- ligand frame in 8 appear relatively unchanged with
1
CD2Cl2 prevented the recording of its H NMR spectrum,
although magnetic moment measurement (polycrystalline
sample) confirmed its S ) 0 spin state. As discussed below,
dissolution of 5 in deuterated DMF or DMSO affords
paramagnetic species due to solvent binding to NiC and such
solutions exhibit broad NMR signals. Metalation of the
sulfurs in 5 was also confirmed by the blue-shift of its νco
band (1538 cm-1) compared to 1 (1510 cm-1).
(Et4N)2[Ni(DMF)2{Ni(NpPepS)}2] (6). The structure of
the anion of the DMF adduct 6 is shown in Figure 7. The
binding of two molecules of DMF to NiC in 5 results in
significant structural rearrangement. Major rearrangement
occurs to accommodate the two additional DMF ligands
coordinated to the NiC center in cis fashion by rotation of
one of the NiTN2S2 units by ∼90° to afford a distorted
octahedral coordination unit around NiC. Although the
average Ni-Namido and Ni-S bond lengths of the NiT sites
in 6 (1.893(3) and 2.1758(12) Å, respectively) remain
unchanged (compared to 1 and 5), the NiC-S bond distances
(av ) 2.4447(12) Å) increase significantly compared with
5 (av ) 2.2368(10) Å) upon expansion of the coordination
sphere. Additionally, this results in a longer Ni‚‚‚Ni separa-
(38) (a) Farmer, P. J.; Solouki, T.; Mills, D. K.; Soma, T.; Russell, D. H.;
Reibenspies, J. H.; Darensbourg, M. Y. J. Am. Chem. Soc. 1992, 114,
4601-4605. (b) Turner, M. A.; Driessen, W. L.; Reedijk, J. Inorg.
Chem. 1990, 29, 3331-3335.
Inorganic Chemistry, Vol. 45, No. 8, 2006 3431

Harrop et al.
Figure 9. ORTEP diagram of [Ni(dppe)Ni(PhPepS)] (10) (50% probability) with the atom-labeling scheme (left). H atoms are omitted for the sake of
clarity. A different view is shown on left showing the dihedral angle between the NiN2S2 and NiS2P2 plane.
only a slight increase in the NiT-S bond length (av )
2.1723(18) Å) presumably due to metalation of sulfur by
NiC. Collectively, the structures of 6 and 8 demonstrate that
minor changes in the ligand design can alter the binding
mode (e.g., cis vs trans coordination) of ligands and reactivity
of metal centers in these model complexes. Complex 8
displays a strong νco band at 1646 cm-1 due to the
O-coordinated DMF ligands and its magnetic moment value
(µeff ) 2.89 µB at 298 K, polycrystalline sample) is consistent
with an S ) 1 ground state.
[Ni(terpy)Ni(NpPepS)] (9). Although we have not com-
pleted structural studies on this model complex due to lack
of suitable crystals, it has been thoroughly characterized by
various spectroscopic techniques and its composition has
been confirmed by microanalytical data. The blue-shift in
the νco band of complex 9 (1531 cm-1) strongly supports
the proposed dinuclear structure, and the ESI-MS data
support the presence of a [Ni(terpy)]2+ moiety bound to a
[Ni(NpPepS)]2- unit. Additional support for a five-coordinate
Ni(II) center in 9 comes from the magnetic susceptibility
studies (µeff ) 3.02 µB at 298 K, polycrystalline sample).
Since 9 exhibits an irreversible reduction at -1.13 V (vs
SCE) in DMF, it is evident that the Ni(I) state is accessible
in this model complex. Although the potential is still outside
the biological range, this property of 9 allows one the
opportunity to study the possibility of CO binding in the
reduced state (Ared-CO mimic). The results of such studies
are discussed in detail in a forthcoming section.
[Ni(dppe)Ni(PhPepS)] (10). The structure of the neutral
dinuclear complex 10 is shown in Figure 9. In this Ni-Ni
model, the two Ni(II) centers are connected via the two
thiolato-S donors of the PhPepS4- ligand frame and both Ni
centers exist in square-planar geometry. The spatial arrange-
ment of the donor atoms of the NiN2S2 portion of this
complex does not change significantly from that in the
monomeric complex 2, and hence, similar Ni-Namido and
Ni-S bond distances (av ) 1.890(17) and 2.150(5) Å,
respectively) are noted for 10. The dihedral angle between
the two Ni(II) square planes in 10 is 111.4° and the Ni‚‚‚Ni
separation is 2.8255(4) Å (Ni‚‚‚Ni in ACS/CODH ) 3.00
Å).6 Coordination of the Nip mimic to the two S-donors of
the PhPepS4- results in a decrease bend of the aryl thiolate
rings due to the shorter bite angle of the cis-dithiolato portion
of the ligand frame (S1-Ni1-S2 ) 79.29(2)°). The bond
angles about the bridged Nip center (Ni2 in Figure 9) in 10
also deviate from the ideal value (P1-Ni2-P2 ) 86.18-
(2)°; P1-Ni2-S1 ) 99.13(2)°) due to steric constraints
imposed by the four phenyl groups of the diphosphine ligand.
The average Ni-S and Ni-P bond distances of the Nip site
in 10 (2.2384(6) and 2.1799(6) Å, respectively) are similar
to those found in other dinuclear Ni complexes with P2S2
coordination spheres.19,22
The dinuclear structure of 10 is readily identified by the
blue-shift of the νco to 1538 cm-1 from 1521 cm-1 in the
case of 2. The two square-planar Ni(II) centers of 10 give
1
rise to a diamagnetic species that exhibits a clean H NMR
spectrum in CDCl3.
Reactivity with 1,10-Phenanthroline. In some of the
earliest studies on ACS/CODH (before any structural analy-
sis), Lindahl and co-workers showed that a portion of the
Ni at the A-cluster site is labile and easily removed with the
bidentate chelator phen.11b This removal of “labile Ni” by
phen completely inhibits the ACS activity but leaves the
CODH activity intact. The phen-treated enzyme also displays
no NiFeC EPR signal. We were therefore curious to
determine whether the sulfur-bridged Ni in the model
complexes such as 6, 8, and 10 can be removed with phen.
Previous studies on a trinuclear model complex reported by
Darensbourg and co-workers, namely [{(BME-DACO)-
Ni}2Ni]Br2, have shown that the Ni(II) center coordinated
by four metallosulfur moieties from the NiN2S2 units in the
complex is indeed removed by phen.23 However, the absence
of key carboxamido groups in the NiN2S2 fragments in these
trinuclear species, as well as the lack of phen reactivity with
a trinuclear complex similar to 6 (and 8) with carboxamido
coordination synthesized by Hegg and co-workers21 prompted
us to study the phen reactivity with our complexes.
Titration of solutions of 6 or 8 in DMF with phen results
in immediate removal of the central Ni (NiC) ions in both
these trinuclear species. The reaction can be followed by
monitoring the electronic absorption spectrum. As shown in
Figure 10, the spectrum completely stops changing only after
addition of 3 mol equiv of phen to 6, suggesting formation
of [Ni(phen)3]2+ and 2 mol equiv of the monomer 1.27b
Similar results were obtained with complex 8. Since no
further change is observed upon addition of a large excess
3432 Inorganic Chemistry, Vol. 45, No. 8, 2006

Analogues of the ActiWe Site of the A-Cluster of ACS/CODH
and 4 affords the respective monomers 1 and 2 and [Cu-
(neo)2]+. Neocuproine exhibits no reaction with the Ni
centers of 6, 8, or 10. Collectively, the phen reactivity of
the Ni complexes 6, 8, and 10 lends further support to the
notion that the “labile Ni” in the enzyme originates from
the Mp site and not the Nid site.11,12 The results also provide
indirect evidence in favor of Ni at the Mp site of the A-cluster
of catalytically actiVe ACS/CODH.
Reactivity of Ni-Cu Models. The Cu(I) sites in all
the synthetic models reported so far exhibit no affinity
toward CO. For example, the dinuclear models synthe-
sized by Riordan and co-workers undergo rupture of the (µ-
SR)2 bridge and breakdown of the dinuclear structure upon
reaction with CO.25 The Ni-Cu dinuclear complex,
[{P(iPr)3Cu}{NiS2N′2}]-, synthesized by Rauchfuss and co-
workers with a coordinatively unsaturated Cu(I) center, does
not exhibit any CO binding.24 Although some of these models
utilize Ni(II)-diamino-dithiolato complexes as the Nid
synthon and hence lack crucial Ni(II)-carboxamido-N
interaction(s),25 the consistent inertness of the Cu(I) centers
in these model complexes indicates a noncatalytic role for
Cu in ACS/CODH.
Figure 10. Changes in the electronic absorption spectrum of (Et4N)2[Ni-
(DMF)2{Ni(NpPepS)}2] (6, 0.087 mM) upon addition of 0.5 mol equiv
aliquots of phen in DMF. Inset: change in absorbance at 437 nm vs mol
equiv of phen.
The Ni-Cu models of the present work, namely 3 and 4,
consist of Nid synthons that include carboxamido ligation to
the Ni(II) center. Both these models exhibit no CO binding
to either metal center nor is any breakdown of the Cu-(µ-
SR)2-Ni core observed upon passage of CO through the
solutions of these complexes. No breakdown of the Cu-(µ-
SR)2-Ni core is observed upon treatment with excess phen
either. Clearly, the dinuclear structures are very stable and
are in accord with results of previous experiments showing
Cu(I) ion as a stronger binder to metallosulfur donors
compared to Ni(II) and Zn(II) ions.23 Although the lack of
reactivity of the Cu(I) centers of 3 and 4 toward CO could
simply arise from coordinative saturation (both tetrahedrally
coordinated), it is important to note that exposure to CO does
not cause any break in the Cu-S bridge to provide a binding
site for CO. This indicates that Cu(I) binds the thiolato sulfurs
of the Nid site quite strongly, and hence, the presence of Cu
at the Mp site in Drennan’s structure could be a consequence
of binding of adventitious metal ions present in the crystal-
lization buffers.11 Indeed, in a recent paper, Darensbourg and
co-workers have examined the metal ion affinity of an
analogous NiN2S2 thiolato complex, ([(BME-DACO)Ni]),
and the results indicate that the affinity decreases in the order
Cu(I) > Ni(II) > Zn(II).23
Reactivity of Ni-Ni Models. Since one of the steps of
the proposed ACS mechanism invokes the formation of a
Ni(I)-CO species responsible for the NiFeC EPR signal,
we have studied the redox properties and CO affinities of
the bridged Ni(II) centers in 6 and 8-10. The redox
behaviors of the models of the Nid sites reported so far
suggest that the Nid site of the A-cluster is unlikely to
participate in any redox process during catalysis and in turn
imply that the Nip site is a candidate for reduction and CO
binding during the ACS catalyzed reaction.19-25 The NiC
centers of the trinuclear species 6 and 8 are ligated to four
metallosulfur ligands and hence resemble the Nip site to a
Figure 11. Changes in the electronic absorption spectrum of [Ni(dppe)-
Ni(PhPepS)] (10, 0.0974 mM) upon mixing with excess phen (25 mol equiv)
in CH2Cl2 at 298 K. Inset: change in absorbance at 594 nm vs time (s).
(∼100 mol equiv) of phen to these solutions, it is evident
that the Ni(II) centers in the Nid mimics 1 and 2 are strongly
coordinated to their dicarboxamido-dithiolato ligand frames
and are resistant to removal by phen.
The reactivity of phen with the dinuclear model 10 is
slightly different from its trinuclear counterparts 6 and 8.27a
Addition of phen to a solution of 10 in CH2Cl2 does remove
the sulfur-bridged Nip model site in this complex resulting
in the formation of 2, [Ni(phen)3]2+, and free dppe in
solution. However, the removal of Nip in 10 requires excess
phen (∼25 mol equiv) and takes nearly 35 min to reach the
end point (beyond which no further change occurs in the
electronic absorption spectrum, Figure 11). The observed
pseudo-first-order rate constant (kobs) for the phen removal
of Nip in dimer 10 is 1.50 × 10-4 s-1. The slower phen
reactivity of 10 compared to that of 6 and 8 presumably arises
from the more stable square-planar low-spin nature of the
Nip site in 10 as opposed to the high-spin octahedral NiC
centers in 6 and 8. Interestingly, treatment of the Ni-Cu
dimers 3 and 4 with phen does not result in any reaction.
However, addition of the Cu(I)-specific chelator neo to 3
Inorganic Chemistry, Vol. 45, No. 8, 2006 3433

Harrop et al.
great extent. Both these models can be chemically reduced
with reductants such as Na2S2O4 and NaBH4 at low temper-
ature (-40 °C) to afford EPR-active species. The X-band
EPR spectrum of the reduced species 6red in DMF glass (100
K) consists of an axial EPR signal (g ) 2.33, 2.09), while
that of 8red is more rhombic (g ) 2.25, 2.12, 2.07). Since 1
and 2 cannot be reduced by Na2S2O4 or NaBH4 (no EPR
signal), it is evident that the Ni(II)C centers in the trinuclear
complexes undergo reduction. The similarity of the EPR
spectra of 6red and 8red with those of other [Ni(I)L4] species
leads us to propose that the coordination geometry about the
Ni(I)C center in these reduced complexes is distorted
tetrahedral.39
Passage of CO into DMF solutions of 6red and 8red results
in the formation of their CO adducts that exhibit intense νco
bands in their solution IR spectra at 1960 and 1971 cm-1,
respectively. These νco values are consistent with terminal
coordination of CO to the Ni(I)C centers of 6red-CO and 8red-
CO much like that proposed in ACS. The reduced Ni(I)S4
complex [Ni(tpttd)]- (tpttd ) 2,2,11,11-tetraphenyl-1,5,8,-
12-tetrathiadodecane) with two alkanethiolato-S donors also
binds CO in a similar manner and exhibits its νco value at
1940 cm-1.40 The νco values for 6red-CO and 8red-CO are
lower than that recorded for the enzyme (1996 cm-1). This
red-shift presumably arises from the enhanced electron
density at the Ni(I) centers ligated by four metallosulfur
donors (instead of the three observed in the enzyme) which
in turn promotes more π back-donation to the π* orbital of
CO. The reduced species and their CO adducts are moder-
ately stable at low temperatures. All efforts to isolate solids
from the reaction mixtures have so far met with little success.
The Ni-Ni model complexes 9 and 10 provided the
opportunity to study the reactions of CO with Ni(I) centers
at modeled Mp sites (with different coordination geometries)
as more accurate mimics of the bimetallic A-cluster subsite.27a
When complex 9 with N3S2 donor set at the Nip site is
reduced with Na2S2O4 in DMF, the product exhibits an axial
EPR spectrum with g ) 2.23 and 2.12 (Figure 12, top panel).
This spectrum is nearly identical to the EPR spectra of
[NiI(terpy)(SR)2]- species with distorted trigonal bipyramidal
geometry.41 It is therefore clear that 9red retains its dinuclear
structure and that the Nip center in 9 is reduced to the Ni(I)
state. Passage of CO through the solution of 9red in DMF
affords 9red-CO that exhibits a strong νco band in its solution
IR spectrum at 2044 cm-1.
Figure 12. X-band EPR spectra of [NiI(terpy)NiII(NpPepS)]- (9red, top)
and [NiI(terpy)(CO)NiII(NpPepS)]- (9red-CO, bottom) in DMF glass at 100
K. Selected g values are indicated. Spectrometer settings: microwave
frequency, 9.50 GHz; microwave power, 20 mW; modulation frequency,
100 kHz; modulation amplitude, 5 G.
to 9red with g ) 2.22, 2.13, and 2.02 (Figure 12, bottom
panel) and resembles the EPR spectra of [NiI(terpy)-
(SR)2(CO)]- species reported by this group.41 For example,
the Ni(I) complex [NiI(terpy)(C6F5S)2(CO)]- exhibits a
rhombic EPR signal in DMF glass with g ) 2.20, 2.15, and
2.02 and displays νco band at 2045 cm-1.41c These data clearly
indicate that the Ni(I) center in 9red-CO exists in a distorted
octahedral geometry and the CO is bound in a terminal
fashion. The reduced complex, 9red, and its CO-adduct, 9red-
CO, are moderately stable at low temperatures and decom-
pose rapidly at room temperature. Prolonged passage of CO
through DMF solutions of 9red also affords [NiI(terpy)-
(CO)2]+.
Since the Nip site of ACS exists in a planar geometry in
the structurally characterized (as isolated) enzyme,6,7 the
modeled Nip site of 10 was a more attractive target to study.
It was expected that phosphine coordination to Nip in 10
would make the Ni(I) oxidation state accessible and result
in a more stable CO adduct. Both expectations have been
met with 10. Complex 10 can be readily reduced by
reductants such as NaBH4 and cobaltocene. The X-band EPR
spectrum of 10red is consistent with a distorted tetrahedral
Ni(I) center with P2S2 coordination and the resulting g values
are close to 2.00 with significant hyperfine splitting origi-
nating from the two nonequivalent 31P nuclei of the dppe
ligand frame.22,42 The reduced species is quite stable at room
Since both 1 and 9 do not show any affinity toward CO,
one can easily conclude that the Ni(I) center binds CO in
9red-CO. The EPR spectrum of 9red-CO is rhombic compared
(39) (a) Craft, J. L.; Mandimutsira, B. S.; Fujita, K.; Riordan, C. G.;
Brunold, T. C. Inorg. Chem. 2003, 42, 859-867. (b) Musie, G.;
Farmer, P. J.; Tuntulani, T.; Reibenspies, J. H.; Darensbourg, M. Y.
Inorg. Chem. 1996, 35, 2176-2183.
(40) Yamamura, T.; Sakurai, S.; Arai, H.; Miyamae, H. J. Chem. Soc.,
Chem. Commun. 1993, 1656-1658.
(41) (a) Marganian, C. A.; Vazir, H.; Baidya, N.; Olmstead, M. M.;
Mascharak, P. K. J. Am. Chem. Soc. 1995, 117, 1584-1594. (b)
Baidya, N.; Olmstead, M. M.; Whitehead, J. P.; Bagyinka, C.;
Maroney, M. J.; Mascharak, P. K. Inorg. Chem. 1992, 31, 3612-
3619. (c) Baidya, N.; Olmstead, M. M.; Mascharak, P. K. Inorg. Chem.
1991, 30, 929-937.
(42) (a) James, T. L.; Cai, L.; Muetterties, M. C.; Holm, R. H. Inorg. Chem.
1996, 35, 4148-4161. (b) Kim, J. S.; Reibenspies, J. H.; Darensbourg,
M. Y. J. Am. Chem. Soc. 1996, 118, 4115-4123. (c) James, T. L.;
Smith, D. M.; Holm, R. H. Inorg. Chem. 1994, 33, 4869-4877. (d)
Bowmaker, G. A.; Boyd, P. D. W.; Campbell, G. K. Inorg. Chem.
1982, 21, 2403-2412.
3434 Inorganic Chemistry, Vol. 45, No. 8, 2006

Analogues of the ActiWe Site of the A-Cluster of ACS/CODH
Figure 14. X-band EPR spectrum of [NiI(dppe)(CO)NiII(PhPepS)]- (10red
CO) in DMF glass at 100 K. Selected g and a values are indicated.
Spectrometer settings: microwave frequency, 9.50 GHz; microwave power,
20 mW; modulation frequency, 100 kHz; modulation amplitude, 5 G.
-
Figure 13. Electronic absorption spectrum of [[NiII(dppe)NiII(PhPepS)]
(10) (solid line) and its reduced species [NiI(dppe)NiII(PhPepS)]- (10red
(dash-dotted line). Reoxidation of 10red to 10 upon exposure to air in CH2-
Cl2 is shown by the dashed line. The complex 10 was reduced with
cobaltocene.
)
a triplet from coupling to two nonequivalent 31P nuclei
(Figure 14). This spectrum resembles the EPR spectrum of
[Ni(psnet)]+, a structurally characterized five-coordinate
complex with distorted square pyramidal P2S2N ligation to
a Ni(I) center.42a The magnetic hyperfine interaction of 31P
nuclei with an unpaired electron of Ni(I) has been shown to
be very susceptible to the coordination geometry around the
metal center.42b For example, the EPR spectrum of the
tetrahedral Ni(I) complex [Ni(PMe3)4]+ (av P-N-P angle
) 109°) consists of an isotropic broad resonance with g )
2.12 with no 31P hyperfine coupling45 while the Ni(I) complex
[Ni(psnet)]+ with distorted square pyramidal structure ex-
hibits a rhombic EPR signal with g1 ) 2.21, g2 ) 2.13, and
g3 ) 2.01 and a1 ) 45 G, a2 ) 40 G, and a3 ) 44 G,
respectively.42a In the present case, three distinct 31P hyperfine
couplings with a values in the range of 30-60 G are noted
with 10red-CO (Figure 14). We therefore assign a {NiIP2S2-
(CO)}-(µ-SR)2-{NiII(N2S2)} formulation to 10red-CO.
Recently, three groups have reported sulfur-bridged di-
nuclear Ni complexes with P2S2 coordination19,20a,22 at the
bridged Ni center (Nip mimic) that exhibit low Ni(I)/Ni(II)
redox potentials.20,22 Unfortunately, very little spectroscopic
data are currently available on the CO adducts of these
complexes in the reduced state. Complex 10 deserves
attention in this regard as the first structurally characterized
Ni-Ni model that includes dicarboxamido-dithiolato liga-
tion (Nid mimic) to a bridged Ni(II) center that (i) can be
reduced to the Ni(I) state and (ii) binds CO in the reduced
state (Nip mimic) much like that proposed for the A-cluster
of ACS/CODH.
temperature. Under anaerobic conditions, one can monitor
the reduction of 10 to 10red in CH2Cl2 with the use of 1 equiv
of cobaltocene. Reaction of 1 equiv of cobaltocene with 10
affords 10red, the species exhibiting the EPR spectrum. The
violet color of 10 changes to light red-brown upon reduction.
When the solution of 10red in CH2Cl2 is exposed to air, it is
immediately reoxidized to 10 in nearly quantitative yield
(Figure 13). This confirms that the (µ-SR)2 bridge remains
intact during reduction.
Passage of CO through a solution of 10red in CH2Cl2 (or
DMF) gives rise to the CO-adduct 10red-CO that exhibits a
strong νco band in its IR spectrum at 1997 cm-1, consistent
with terminally bound CO to the Ni(I)p center. Complete
removal of the solvent affords a dark red solid which also
displays the same νco band in KBr matrix (Supporting
Information).43 Since the νco value of 10red-CO is very close
to the enzyme value of 1996 cm-1, it is reasonable to
conclude that the Nip center in the enzyme binds CO in the
+1 oxidation state. In [{Ni(CO)2}{NiS2N′2}]2- (Figure 2a),
two molecules of CO are bound to a Ni(0) center in terminal
fashion.24 This Nip mimic displays two νco bands at 1948
and 1866 cm-1. Holm and co-workers have reported a Ni-
(0) complex [Ni(bpy)(CO)2] (bpy ) 2,2′-bipyridine) which
exhibits νco bands at 1872 and 1973 cm-1 (KBr matrix).44
Since these νco values are all lower than that displayed by
10red-CO, it is evident that the latter species does contain
Ni(I) and not Ni(0) at the Nip site. As mentioned above, the
Nid site of 10 is quite resistant to reduction. Indeed, the νco
values arising from the ligated carboxamido groups at the
Nid sites of 10 and 10red-CO are very close to each other
and further support the presence of Ni(II) at the Nid site in
10red-CO.
In the absence of the Fe4S4 portion of the A-cluster in the
sulfur-bridged Ni-Ni models, it is impossible to assess the
effect(s) of the iron-sulfur cluster on the chemical and redox
properties of the Nip center. Although recent studies have
indicated that electron flow to and from the Fe4S4 cluster is
too slow compared to the rate of methyl transfer,46 the
The EPR spectrum of 10red-CO in DMF glass is rhombic
with g1 ) 2.20, g2, ) 2.12, g3 ) 2.05; each line is split into
(43) The red solid is moderately stable under anaerobic conditions; however,
it decomposes slowly in solution and, to date, we have not been able
to characterize it by structural studies. The EPR spectrum of a solution
of the freshly isolated red solid in DMF (same as Figure 14) confirms
that the solid is indeed 10red-CO.
(45) Gleizes, A.; Dartiguenave, M.; Dartiguenave, Y.; Galy, J.; Klein, H.
F. J. Am. Chem. Soc. 1977, 99, 5187-5189.
(46) Tan, X.; Sewell, C.; Yang, Q.; Lindahl, P. A. J. Am. Chem. Soc. 2003,
125, 318-319.
(44) Tucci, G. C.; Holm, R. H. J. Am. Chem. Soc. 1995, 117, 6489-6496.
Inorganic Chemistry, Vol. 45, No. 8, 2006 3435

Harrop et al.
proposed mechanisms of ACS activity mostly involve redox
changes at the Fe4S4 cluster during key steps of the catalytic
cycle.5,6,47,48 Theoretical studies suggest that the Ni(0) state49
is only stabilized by either removal of the cluster15 or by
the presence of a neighboring reduced iron-sulfur cluster
[Fe4S4]1+ (S ) 1/2).48 Clearly, the next generation models
of the ACS A-cluster have to incorporate the Fe4S4 cluster
in order to address these issues.47,50 Such attempts are in
progress in this laboratory at this time.
(Nip mimics) appear quite capable of binding substrates such
as CO when in the reduced Ni(I) state but not in the Ni(II)
state. The IR spectra of such CO adducts exhibit νco bands
in the range 1960-2044 cm-1, indicating terminal Ni(I)-
CO coordination similar to that proposed in the enzyme (νco
) 1996 cm-1). Since the Ni-Ni models of this work (such
as 9 and 10) are devoid of the strong dipolar coupling of the
Nip site to the Fe4S4 cluster, the EPR spectra of the CO-
adducts such as 10red-CO do not resemble the NiFeC EPR
signal. The removal of Nip sites from selected models by
phen provides strong evidence in favor of Nip being the
source of “labile Ni” in the enzyme. No reactivity toward
CO has been noted with the dinuclear Ni-Cu models (3 and
4). Collectively, these observations lend support to the
present notion that the Mp site in catalytically active ACS/
CODH is occupied by Ni.
Conclusions
The results of the modeling work reported here reveal
valuable insight into the novel A-cluster site involved in
acetyl CoA synthesis by ACS/CODH. For example, it is quite
evident that coordination of both carboxamido nitrogen and
thiolato sulfur stabilizes the Ni(II) state to a great extent (like
in 1 and 2) and hence the Nid site in the enzyme is not
expected to participate in any redox chemistry. Binding of
potential substrates such as CO at this site is also unlikely.
Furthermore, Ni(II) centers bridged to metallosulfur moieties
Acknowledgment. T.C.H. received financial support from
NIH IMSD Grant No. GM58903.
Supporting Information Available: FTIR spectra of 10 and
10red-CO in KBr matrix (Figure S1), machine parameters, crystal
data, and data collection parameters for all the complexes (Table
S1), selected bond distances and angles are reported (Table S2),
and X-ray crystallographic data (in CIF format) and tables for the
structure determination of complexes 2, 3‚0.5Et2O‚0.5H2O, 4‚H2O,
5‚DMF, 6‚3DMF, 8, and 10‚CH2Cl2. This material is available free
of charge via the Internet at http://pubs.acs.org.
(47) Hegg, E. L. Acc. Chem. Res. 2004, 37, 775-783.
(48) Amara, P.; Volbeda, A.; Fontecilla-Camps, J. C.; Field, M. J. J. Am.
Chem. Soc. 2005, 127, 2776-2784.
(49) Lindahl, P. A. J. Biol. Inorg. Chem. 2004, 9, 516-524.
(50) In a recent paper, Holm and co-workers have reported the results of
such an attempt. However, only complexes of the thiolato-bridged
[Fe4S4]-NiL type have been isolated. See: Rao, P. V.; Bhaduri, S.;
Jiang, J.; Hong, D.; Holm, R. H. J. Am. Chem. Soc. 2005, 127, 1933-
1945.
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