On [Fe4S4]2+-(μ2-SR)-M II bridge formation in the synthesis of an A-cluster analogue of carbon monoxide dehydrogenase/acetylcoenzyme A synthase

Article abstract of DOI:10.1021/ja040222n

The construction of a synthetic analogue of the A-cluster of carbon monoxide dehydrogenase/ acetylcoenzyme synthase, the site of acetylcoenzyme A formation, requires as a final step the formation of an unsupported [Fe ₄S₄]-(μ₂-SR)-Ni^II bridge to a preformed cluster. Our previous results (Rao, P. V.; Bhaduri, S.; Jiang, J.; Holm, R. H. Inorg. Chem. 2004, 43, 5833) and the work of others have addressed synthesis of dinuclear complexes relevant to the A-cluster. This investigation concentrates on reactions pertinent to bridge formation by examining systems containing dinuclear and mononuclear Ni^II complexes and the 3:1 site-differentiated clusters [Fe₄S₄(LS₃) L′]^2- (L′ = TfO^- (14), SEt (15)). The system 14/[{Ni(L_O-S₂N₂)}M(SCH₂CH ₂PPh₂)]⁺ results in cleavage of the dinuclear complex and formation of [{Ni(L_O-S₂N₂)}-Fe ₄S₄(LS₃)]^- (18), in which the Ni^II complex binds at the unique cluster site with formation of a Ni(μ₂-SR)₂Fe bridge rhomb. Cluster 18 and the related species [{Ni(phma)}Fe₄S₄(LS₃)]^3- (19) are obtainable by direct reaction of the corresponding cis-planar Ni ^II-S₂N₂ complexes with 14. The mononuclear complexes [M(pdmt)(SEt)]^- (M = Ni^II, Pd^II) with 14 in acetonitrile or Me₂SO solution react by thiolate transfer to give 15 and [M₂(pdmt)₂]. However, in dichloromethane the Ni^II reaction product is interpreted as [{Ni(pdmt)(μ₂- SEt)}Fe₄S₄(LS₃)]^2- (20). Reaction of Et₃NH⁺ and 15 affords the double cubane [{Fe ₄S₄(LS₃)}₂(μ₂-SEt)] ^3- (21). Cluster 18 contains two mutually supportive Fe-(μ₂-SR)-Ni^II bridges, 19 exhibits one strong and one weaker bridge, 20 has one unsupported bridge (inferred from the ¹H NMR spectrum), and 21 has one unsupported Fe-(μ₂-SR)-Fe bridge. Bridges in 18, 19, and 21 were established by X-ray structures. This work demonstrates that a bridge of the type found in the enzyme A-clusters is achievable by synthesis and implies that more stable, unsupported single thiolate bridges may require reinforcement by an additional covalent linkage between the Fe₄S₄ and nickel-containing components. (LS₃ = 1,3,5-tris((4,6-dimethyl-3-mercaptophenyl)thio)-2,4,6-tris(p- tolylthio)benzene(3-); L_O-S₂N₂ = N,N′-diethyl-3,7-diazanonane-1,9-dithiolate(2-); pdmt = pyridine-2,6-methanedithiolate(2-); phma = N,N′-1,2-phenylenebis(2- acetylthio)-acetamidate(4-); TfO = triflate.).

Full text of DOI:10.1021/ja040222n

Published on Web 01/20/2005
On [Fe4S4]2+-(µ2-SR)-MII Bridge Formation in the Synthesis
of an A-Cluster Analogue of Carbon Monoxide
Dehydrogenase/Acetylcoenzyme A Synthase
P. Venkateswara Rao, Sumit Bhaduri, Jianfeng Jiang, Daewon Hong, and
R. H. Holm*
Contribution from the Department of Chemistry and Chemical Biology, HarVard UniVersity,
Cambridge, Massachusetts 02138
Received September 22, 2004; E-mail: holm@chemistry.harvard.edu
Abstract: The construction of a synthetic analogue of the A-cluster of carbon monoxide dehydrogenase/
acetylcoenzyme synthase, the site of acetylcoenzyme A formation, requires as a final step the formation
of an unsupported [Fe4S4]-(µ2-SR)-NiII bridge to a preformed cluster. Our previous results (Rao, P. V.;
Bhaduri, S.; Jiang, J.; Holm, R. H. Inorg. Chem. 2004, 43, 5833) and the work of others have addressed
synthesis of dinuclear complexes relevant to the A-cluster. This investigation concentrates on reactions
pertinent to bridge formation by examining systems containing dinuclear and mononuclear NiII complexes
and the 3:1 site-differentiated clusters [Fe4S4(LS3)L′]2- (L′ ) TfO- (14), SEt (15)). The system 14/[{Ni(LO-
S2N2)}M(SCH2CH2PPh2)]+ results in cleavage of the dinuclear complex and formation of [{Ni(LO-S2N2)}-
Fe4S4(LS3)]- (18), in which the NiII complex binds at the unique cluster site with formation of a Ni(µ2-
SR)2Fe bridge rhomb. Cluster 18 and the related species [{Ni(phma)}Fe4S4(LS3)]3- (19) are obtainable by
direct reaction of the corresponding cis-planar NiII-S2N2 complexes with 14. The mononuclear complexes
[M(pdmt)(SEt)]- (M ) NiII, PdII) with 14 in acetonitrile or Me2SO solution react by thiolate transfer to give
15 and [M2(pdmt)2]. However, in dichloromethane the NiII reaction product is interpreted as [{Ni(pdmt)(µ2-
SEt)}Fe4S4(LS3)]2- (20). Reaction of Et3NH+ and 15 affords the double cubane [{Fe4S4(LS3)}2(µ2-SEt)]3-
(21). Cluster 18 contains two mutually supportive Fe-(µ2-SR)-NiII bridges, 19 exhibits one strong and
one weaker bridge, 20 has one unsupported bridge (inferred from the 1H NMR spectrum), and 21 has one
unsupported Fe-(µ2-SR)-Fe bridge. Bridges in 18, 19, and 21 were established by X-ray structures. This
work demonstrates that a bridge of the type found in the enzyme A-clusters is achievable by synthesis and
implies that more stable, unsupported single thiolate bridges may require reinforcement by an additional
covalent linkage between the Fe4S4 and nickel-containing components. (LS3 ) 1,3,5-tris((4,6-dimethyl-3-
mercaptophenyl)thio)-2,4,6-tris(p-tolylthio)benzene(3-); LO-S2N2 ) N,N′-diethyl-3,7-diazanonane-1,9-dithi-
olate(2-); pdmt ) pyridine-2,6-methanedithiolate(2-); phma ) N,N′-1,2-phenylenebis(2-acetylthio)-
acetamidate(4-); TfO ) triflate.)
Introduction
Bifunctional carbon monoxide dehydrogenases (CODH/ACS)
contain two catalytic centers composed of Ni-Fe-S clusters.1-3
The reaction CO + H2O h CO2 + 2H+ + 2e- is catalyzed at
the C-cluster. X-ray structures of enzymes from two different
organisms reveal a NiFe3S4,5 core with a NiFe3S4 cuboidal
portion to which is attached an exo-iron atom.4-6 At the
A-cluster, acetylcoenzyme A is synthesized from coenzyme A,
a methyl group derived from a corrinoid protein, and carbon
monoxide. The site, shown in Figure 1, has the minimal
formulation [Fe4S4]-(µ2-SCys)-[Ni((µ2-SCys)2Gly)Ni]. From
Figure 1. Structure of the bridged assembly [Fe4S4]-(µ2-SCys)-Nip-(µ2-
S
Cys)2-Nid, which is the A-cluster of Moorella thermoacetica (d ) distal,
p ) proximal to the cluster). The distal NiII atom is bound by a deprotonated
Cys-Gly-Cys sequence; one ligand at the Nip site is unidentified.
(1) Ragsdale, S. W.; Kumar, M. Chem. ReV. 1996, 96, 2515-2539.
(2) Grahame, D. A. Trends Biochem. Sci. 2003, 28, 221-224.
(3) Drennan, C. L.; Peters, J. W. Curr. Opin. Struct. Biol. 2003, 13, 220-226.
(4) Drennan, C. L.; Heo, J.; Sintchak, M. D.; Schreiter, E.; Ludden, P. W.
Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 11973-11978.
(5) Dobbek, H.; Svetlitchnyi, V.; Gremer, L.; Huber, R.; Meyer, O. Science
2001, 293, 1281-1285.
crystallographic and X-ray absorption spectroscopic results on
enzymes from Moorella thermoacetica and Carboxydothermus
hydrogenoformans, the NiII atom distal to the cluster is
coordinated in a cis-planar NiII-S2N2 arrangement. The proxi-
mal NiII atom is part of a Ni2(µ2-SR)2 bridge rhomb and is
implicated in a tetrahedral NiII(µ2-SCys)3L coordination unit with
(6) Dobbek, H.; Svetlitchnyi, V.; Liss, J.; Meyer, O. J. Am. Chem. Soc. 2004,
126, 5382-5387.
9
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J. AM. CHEM. SOC. 2005, 127, 1933-1945
1933

A R T I C L E S
Rao et al.
an unidentified ligand.7-9 This structure also appears to apply
to acetyl-CoA decarbonylase/synthase from Methanosarcina
thermophilia.10 In addition, structures have been reported in
which Cu(I)11,12 and Zn(II)8 atoms occupy the proximal site.
However, current evidence is persuasive in establishing NiII as
the native metal in this site.8,13-15
nation. In one instance, formation of this entity with M ) FeII
was indicated by H NMR shifts, but the lability of the bridge
precluded specific recognition and isolation of the desired
species.20 Using a de novo designed helix-loop-helix peptide
as a scaffold, the unit [Fe4S4]2+-(µ2-SCys)-NiII(SCys)(NHis)2 was
constructed in a process in which the NiII component was added
to the peptide containing the cluster.21 Bridge formation is
1
We are engaged in the problem of constructing analogues of
both the C-cluster and A-cluster of CODH/ACS, a prerequisite
to subsequent structural and reactivity studies. Recent progress
on the C-cluster problem is described elsewhere.16 Here we
proceed on the basis of an Fe4S4-Ni-Ni A-cluster. As set out
earlier,17 synthesis of an A-cluster analogue involves three
supported by EXAFS results.22 Sulfido-bridged units [Fe4S4]2+
-
(µ2-S)-FeIII have been isolated and identified by H NMR
isotropic shifts.23,24 The only crystallographically proven in-
stances of thiolate bridging to an Fe4S4 cluster in stable species
are found with [{NiII(LO-S2N2)}Fe4S4I3]- 25 and [{NiII(LO-
S2N2)}2Fe4S4L2] (L ) I-, RS-),26 where the NiII complex
functions as a bidentate ligand in the development of five-
coordinate iron sites. Here we describe our observations pursuant
to step (iii), the formation of bridged clusters relevant to the
A-cluster structure.
1
II
steps: (i) preparation of a cis-planar Nid -S2N2 unit with
II
physiologically realistic coordination; (ii) introduction of a Nip
bridging atom to afford a doubly bridged Ni2(µ2-SR)2 rhomb;
II
and (iii) formation of a [Fe4S4]-(µ2-SR)-Nip bridge to a
preformed cubane-type cluster with the desired stereochemistry
at the proximal site. Step (i) has been addressed in two
independent studies. Krishnan and Riordan18 have prepared a
dianionic NiII-S2N2 complex ligated by a substituted Cys-Gly-
Cys peptide. In our work, we have synthesized and structurally
characterized a mononuclear NiII complex derived from a
tetradeprotonated diamidodithiolate ligand.17 Both complexes
have the 6-5-5 chelate ring size pattern of the A-cluster. The
mean bond lengths Ni-S (2.17 Å) and Ni-N (1.88 Å) in [Ni-
Experimental Section
Preparation of Compounds. All operations were conducted under
a pure dinitrogen atmosphere box. Numerical designations of complexes
and abbreviations are given in Chart 1. All solvents were distilled prior
to use, as described elsewhere.17 Selected compounds were identified
by electrospray mass spectrometry (percentages refer to peak intensities
relative to the most intense fragment peak). Certain compounds were
analyzed; 12 compounds were characterized by X-ray structure
determinations.
II
(L-655)]2- agree well with values at the Nid protein site.7,9
[Pt(SCH2CH2PPh2)(PPh3)Cl] (1). To a solution of [PtCl2(PPh3)2]
(0.451 g, 0.57 mmol) in 30 mL of dichloromethane was added slowly
Step (ii) has been pursued by the preparation of several dinuclear
complexes which contain nonplanar NiII (µ2-SR)2 rhombs.17-19
2
27
a solution of HSCH2CH2PPh2 (0.148 g, 0.60 mmol) in 5 mL of
For example, in this laboratory we have prepared and structurally
defined the complexes [{Ni(L-655)}Ni(R2PCH2CH2PR2)] (R )
Et, Ph), in which phosphine-bound NiII occupies what would
be the proximal site in a fully developed analogue assembly.
We have also structurally defined bridging modes between
dichloromethane. The color of the solution turned from yellow to
yellow-orange. The mixture was stirred for 3 h, and the volume was
reduced to 5 mL. Hexanes (20 mL) were added, and the solution was
allowed to stand at -20 °C overnight. The product was filtered off,
washed with hexanes, and dried; it was obtained as 0.330 g (78%) of
yellow microcrystals. Mass spectrum: m/z 702.0 ({M - Cl-}+, 100%).
Anal. Calcd for C32H29ClP2PtS: C, 52.07; H, 3.96; S, 4.34. Found: C,
52.25; H, 4.06; S, 4.46.
several other cis-planar NiII-S2N2 complexes and NiII, CuI,II
,
ZnII, and HgII. When these results and those of others are
compiled, over 20 different bridging modalites involving one
or both thiolate sulfur atoms emerge.17 One of these, NiII (µ2-
(Bu4N)[Pd(pdmt)(SEt)] ((Bu4N)[2]). To an orange suspension of
[Pd(pdmt)]228 (0.110 g, 0.20 mmol) in 30 mL of acetonitrile were added
NaSEt (0.034 g, 0.40 mmol) and Bu4NBr (0.129 g, 0.40 mmol). Upon
stirring, the orange-yellow slurry turned to a transparent orange-red
solution in 3 h, after which the solution was filtered through Celite
and the solvent removed in vacuo. The orange oil was triturated with
ether to afford an orange-red solid. Recrystallization of the solid from
acetonitrile/ether afforded the product as 0.135 g (54%) of orange
2
SR)2, has been integrated into the native catalytic site.
Step (iii) appears to be most precarious in the construction
of an analogue site cluster. Thus far, the minimal construct
[Fe4S4]2+-(µ2-SR)-M, where M is a mononuclear entity, has
not been directly demonstrated by an X-ray structure determi-
(7) Russell, W. K.; Stålhandske, C. M. V.; Xia, J.; Scott, R. A.; Lindahl, P. A.
J. Am. Chem. Soc. 1998, 120, 7502-7510.
1
crystals. H NMR (CD3CN, anion): δ 1.18 (t, 3), 2.20 (q, 2), 4.20 (s,
4), 7.14 (d, 2), 7.40 (t, 1). Mass spectrum: m/z 332 (M-, 100%). Anal.
Calcd for C25H48N2PdS3: C, 51.83; H, 8.35; N, 4.84; S, 16.61. Found:
C, 51.68; H, 8.31; N, 4.73; S, 16.55.
(8) Darnault, C.; Volbeda, A.; Kim, E. J.; Legrand, P.; Verne`de, X.; Lindahl,
P. A.; Fontecilla-Camps, J. C. Nature Struct. Biol. 2003, 10, 271-279.
(9) 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. 2004, 101,
446-451.
[{Ni(LO-S2N2)}FeCl2] (4). To a solution of [Ni(LO-S2N2)]26 (0.062
g, 0.20 mmol) in 5 mL of acetonitrile was added a pale suspension of
FeCl2 (0.026 g, 0.20 mmol) in 2 mL of acetonitrile. The mixture was
stirred for 2 h. The dark red solution was filtered through Celite, and
(10) Funk, T.; Gu, W.; Friedrich, S.; Wang, H.; Gencic, S.; Grahame, D. A.;
Cramer, S. P. J. Am. Chem. Soc. 2004, 126, 88-95.
(11) Doukov, T. I.; Iverson, T. M.; Seravalli, J.; Ragsdale, S. W.; Drennan, C.
L. Science 2002, 298, 567-572.
(12) Seravalli, J.; Gu, W.; Tam, A.; Strauss, E.; Begley, T. P.; Cramer, S. P.;
Ragsdale, S. W. Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 3689-3694.
(13) Bramlett, M. R.; Tan, X.; Lindahl, P. A. J. Am. Chem. Soc. 2003, 125,
9316-9317.
(20) Liu, H. Y.; Scharbert, B.; Holm, R. H. J. Am. Chem. Soc. 1991, 113, 9529-
9539.
(14) Schenker, R. P.; Brunold, T. C. J. Am. Chem. Soc. 2003, 125, 13962-
(21) Laplaza, C. E.; Holm, R. H. J. Am. Chem. Soc. 2001, 123, 10255-10264.
(22) Musgrave, K. B.; Laplaza, C. E.; Holm, R. H.; Hedman, B.; Hodgson, K.
O. J. Am. Chem. Soc. 2002, 124, 3083-3092.
13963.
(15) Seravalli, J.; Xiao, Y.; Gu, W.; Cramer, S. P.; Antholine, W. E.; Krymov,
V.; Gerfern, G. J.; Ragsdale, S. W. Biochemistry 2004, 43, 3944-3955.
(16) Panda, R.; Zhang, Y.; McLauchlan, C. C.; Venkateswara Rao, P.; Tiago
de Oliveira, F. A.; Mu¨nck, E.; Holm, R. H. J. Am. Chem. Soc. 2004, 126,
6448-6459.
(23) Cai, L.; Holm, R. H. J. Am. Chem. Soc. 1994, 116, 7177-7188.
(24) Zhou, C.; Cai, L.; Holm, R. H. Inorg. Chem. 1996, 35, 2767-2772.
(25) Osterloh, F.; Saak, W.; Haase, D.; Pohl, S. Chem. Commun. 1996, 777-
778.
(17) Rao, P. V.; Bhaduri, S.; Jiang, J.; Holm, R. H. Inorg. Chem. 2004, 43,
5833-5849.
(18) Krishnan, R.; Riordan, C. G. J. Am. Chem. Soc. 2004, 126, 4484-4485.
(19) Wang, Q.; Blake, A. J.; Davies, E. S.; McInnes, E. J. L.; Wilson, C.;
Schro¨der, M. Chem. Commun. 2003, 3012-3013.
(26) Osterloh, F.; Saak, W.; Pohl, S. J. Am. Chem. Soc. 1997, 119, 5648-
5656.
(27) Chatt, J.; Dilworth, J. R.; Schmutz, J. A. J. Chem. Soc., Dalton Trans.
1979, 1595-1599.
(28) Ma´rquez, V. E.; Anacona, J. R. Polyhedron 1997, 16, 1931-1935.
9
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Bridge Formation in A-Cluster Analogue of CODH/ACS
A R T I C L E S
Chart 1. Designation of Complexes and Abbreviations
ether was diffused into the filtrate. The product was obtained as 0.052
g (62%) of dark red blocklike crystals. Mass spectrum: m/z 307 ({M
- FeCl2 + H+}+, 100%). Anal. Calcd for C11H24Cl2FeN2NiS2: C,
30.45; H, 5.58; N, 6.46; S, 14.78. Found: C, 30.39; H, 5.46; N, 6.40;
S, 14.64.
[{Ni(LO-S2N2)}2Ni][Ni(PPh3)Cl3]2 ([5][Ni(PPh3)Cl3]2). To a solution
of [Ni(LO-S2N2)] (0.031 g, 0.10 mmol) in 5 mL of acetonitrile was
added a blue-green suspension of [Ni(PPh3)2Cl2] (0.066 g, 0.10 mmol)
in 3 mL of acetonitrile. The mixture was stirred for 10 min. The dark
brown-green solution was treated with a suspension of NaPF6 (0.017
g, 0.10 mmol) in 1 mL of acetonitrile and stirred for 2 h. The mixture
was filtered through Celite, and the filtrate was concentrated to dryness.
The dark brown-green solid was dissolved in acetonitrile and filtered,
and ether was diffused into the filtrate. The product was obtained as
0.041 g (54%) of brown-green platelike crystals. Mass spectrum: m/z
336 ({M2+/2}, 100%).
[{Ni(LO-S2N2)}Pd(PPh3)Cl](PF6) ([6](PF6)). To a solution of [Ni-
(LO-S2N2)] (0.053 g, 0.17 mmol) in 5 mL of acetonitrile was added an
orange suspension of trans-[Pd(PPh3)2Cl2] (0.119 g, 0.17 mmol) in 5
mL of acetonitrile. The mixture was stirred for 10 min. The dark red
solution was treated with a suspension of NaPF6 (0.029 g, 0.17 mmol)
in 2 mL of acetonitrile and stirred for 2.5 h. The mixture was filtered
through Celite, and the filtrate was evaporated to dryness. The red solid
was dissolved in acetonitrile and filtered, and ether was diffused into
the filtrate. The product was obtained as 0.107 g (73%) of red platelike
crystals. Mass spectrum: m/z 711 (M+, 100%). Anal. Calcd for C29H39-
ClF6N2NiP2PdS2: C, 40.68; H, 4.59; N, 3.37; S, 7.49. Found: C, 40.61;
H, 4.63; N, 3.38; S, 7.37.
[{Ni(LO-S2N2)}Pt(PPh3)Cl](PF6) ([7](PF6)). The preceding prepara-
tion was followed on the same scale with use of trans-[Pt(PPh3)2Cl2].
The product was obtained as 0.125 g (78%) of red platelike crystals.
Mass spectrum: m/z 799 (M+, 70%).
[{Ni(LO-S2N2)}Ni(SCH2CH2PPh2)](PF6) ([8](PF6)). To a suspen-
sion of [Ni(LO-S2N2)] (0.031 g, 0.10 mmol) in 6 mL of THF was added
dropwise a dark red solution of [Ni(SCH2CH2PPh2)Cl]229 (0.034 g, 0.05
mmol) in 5 mL of THF. The initial suspension slowly disappeared,
and a brownish-red solution formed. To the solution was added a
suspension of NaPF6 (0.017 g, 0.10 mmol) in 2 mL of THF; the dark
red solution was stirred for 3 h. The mixture was filtered through Celite,
and the filtrate was concentrated to dryness. A red solid was extracted
from the residue with dichloromethane, the extract was filtered, and
ether was diffused into the filtrate. The product was obtained as 0.042
g (55%) of red crystals. Mass spectrum: m/z 611 (M+, 100%). Anal.
Calcd for C25H38F6N2Ni2P2S3: C, 39.71; H, 5.07; N, 3.79; S, 12.72.
Found: C, 39.63; H, 5.15; N, 3.75; S, 12.70.
[{Ni(LO-S2N2)}Pd(SCH2CH2PPh2)](PF6) ([9](PF6)). To a solution
of [Ni(LO-S2N2)] (0.061 g, 0.20 mmol) in 3 mL of acetonitrile was
(29) Gerdau, T.; Klein, W.; Kramolowsky, R. Cryst. Struct. Commun. 1982,
11, 1663-1669.
9
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A R T I C L E S
Rao et al.
added a suspension of [Pd(SCH2CH2PPh2)(PPh3)Cl]30 (0.130 g, 0.20
mmol) in 3 mL of acetonitrile. To the red solution was added a
suspension of NaPF6 (0.034 g, 0.20 mmol) in 3 mL of acetonitrile.
The dark red solution was stirred for 3 h and filtered through Celite,
and the filtrate was concentrated to 5 mL. Ether was diffused into the
filtrate. The product was collected as 0.120 g (75%) of red crystals.
Mass spectrum: m/z 659 (M+, 100%). Anal. Calcd for C25H38F6N2-
Pd2P2S3: C, 37.35; H, 4.76; N, 3.48; S, 11.97. Found: C, 37.46; H,
4.83; N, 3.50; S, 11.90.
[{Ni(LO-S2N2)}Pt(SCH2CH2PPh2)](PF6) ([10](PF6)). To a solution
of [Ni(LO-S2N2)] (0.061 g, 0.20 mmol) in 5 mL of acetonitrile was
added a suspension of [Pt(SCH2CH2PPh2)(PPh3)Cl] (0.148 g, 0.20
mmol) in 5 mL of acetonitrile. The red solution was treated with a
suspension of NaPF6 (0.034 g, 0.20 mmol) in 2 mL of acetonitrile,
and the dark red solution was stirred for 3 h. The mixture was filtered
through Celite, and ether was diffused into the filtrate. The product
was obtained as 0.137 g (77%) of red crystals. Mass spectrum: m/z
747 (M+, 100%).
[{Ni(L-655)}Pt(PPh3)2] ([13]). Method A: To a solution of (Et4N)2-
[Ni(L-655)]17 (0.040 g, 0.075 mmol) in 3 mL of acetonitrile was added
a suspension of [Pt(SCH2CH2PPh2)(PPh3)Cl] (0.055 g, 0.075 mmol)
in 6 mL of acetonitrile; THF (6 mL) was added, and mixture was stirred
for 5 h. The mixture was filtered through Celite, and the filtrate was
concentrated to dryness. The orange solid was washed twice with
acetonitrile and once with ether. An orange solid was extracted from
the residue with dichloromethane, the extract was filtered, and ether
was diffused into the filtrate. The product was obtained as 0.022 g
(44%) of red crystals. Mass spectrum: m/z 997 ({M + H+}+, 100%).
Anal. Calcd for C43H40N2NiO2P2PtS2: C, 51.82; H, 4.05; N, 2.81; S,
6.43. Found: C, 51.43; H, 4.02; N, 2.73; S, 6.64. Method B: To a
solution of (Et4N)2[Ni(L-655)] (0.027 g, 0.05 mmol) in 5 mL of
acetonitrile was added a suspension of trans-[Pt(PPh3)2Cl2] (0.040 g,
0.05 mmol) in 2 mL of acetonitrile; THF (2 mL) was added, and mixture
was stirred for 2 h. The workup procedure of method A was followed.
The product was obtained as 0.028 g (56%) of red crystals. Mass
spectrum: m/z 997 ({M + H+}+, 60%).
(Et4N)3[Fe4S4(LS3)(bdt)] ((Et4N)3[17]). To a solution of (Bu4N)2-
[Fe4S4(LS3)(OTf)]31 (0.100 g, 0.051 mmol) in 15 mL of acetonitrile
were added a suspension of Na2(bdt) (0.010 g, 0.051 mmol) in 3 mL of
acetonitrile and a solution of Et4NCl (0.025 g, 0.15 mmol) in 2 mL of
acetonitrile. The mixture was stirred for 10 h. A brown-black solid
was collected and washed with ether. The product was obtained as 0.058
g (62%) of brown-black solid. 1H NMR (Me2SO, anion): δ 10.01 (Ph),
8.35 (5-H), 7.18, 6.61 (2′-H, 3′-H), 4.09, 3.48 (6-Me, 4-Me), 2.27 (4′-
Me).
0.05 mmol) in 2 mL of acetonitrile. The mixture was stirred for 1 h
and filtered through Celite. Ether was diffused into the filtrate, affording
the product as 0.087 g (87%) of dark black crystals. Mass spectrum:
m/z 1056.7 ({M - H2LS3}-, 50%). 1H NMR (CD3CN, anion): δ 13.2
(SCH2), 8.30 (Ph-H), 8.25 (5-H), 7.16, 6.75 (2′-H, 3′-H), 6.49 (Ph-H),
4.86 (br, 2-H), 3.94, 3.68 (6-Me, 4-Me), 2.26 (4′-Me).
X-ray Structure Determinations. Twelve compounds were struc-
turally identified by X-ray crystallography. Diffraction quality crystals
were obtained as follows: layering hexanes on a dichloromethane solu-
tion, 1 (orange blocks, 1 d); layering ether onto or vapor diffusion of
ether into acetonitrile solutions, (Bu4N)[2] (orange blocks), 4 (dark red
blocks), [5][Ni(PPh3)Cl3]2 (brown-green plates), [6,7,9,10](PF6) (red
plates), (Bu4N)[18]‚1.5MeCN‚0.5Et2O (dark brown plates) (all 1-3 d);
[8](PF6), 13‚CH2Cl2, vapor diffusion of ether in dichloromethane
solutions. (Bu4N)3[21]‚3MeCN was obtained by the reaction of (Bu4N)2-
[Fe4S4(LS3)(SEt)] with (Et3NH)(OTf) in acetonitrile, removal of solvent,
and crystallization of the solid residue from acetonitrile/ether. Crystals
were coated in grease and mounted on a Siemens (Bruker) SMART
CCD area detector instrument with Mo KR radiation. Data were collec-
ted at either 193 or 213 K with ω scans of 0.3°/frame, with 30 s/frame
(except for (Bu4N)[18]‚1.5MeCN‚0.5Et2O, which was collected at 60
s/frame), such that 1271 frames were collected for a hemisphere of
data. The first 50 frames were re-collected at the end of the data collec-
tion to monitor for decay; no significant decay was found for any com-
pound. Data out to 2θ of 56.7° were used for (Bu4N)[2] and [6,7,10]-
(PF6) and to 2θ of 50.0° for [9](PF6); for the remaining compounds
data out to 2θ of 45° were used because of the low-quality high-angle
data. Cell parameters were retrieved using SMART software and refined
on all observed reflections between 2θ of 3° and the upper thresholds.
Data reduction was performed with SAINT, which corrects for Lorentz
polarization and decay. Absorption corrected were applied with SADABS,
as described by Blessing.37 Space groups of all compounds were assign-
ed unambiguously by analysis of symmetry and systematic absences
determined by XPREP. Crystal parameters are listed in Table S1.38
All structures were solved by direct methods with SHELXS-97 and
subsequently refined against all data in the 2θ ranges by full-matrix
least squares on F 2. Hydrogen atoms were attached at idealized
positions on carbon atoms. The program PLATON was used to check
for missing symmetry. Final agreement factors are given in Table S1.38
For the compound (Bu4N)[18]‚1.5MeCN‚0.5Et2O, there are two
independent anions in the asymmetric unit. In one anion, a phenyl ring
is disordered over two positions. Solvent molecules are disordered and
were refined isotropically. No disorder was evident in any other
structure. Crystals of (Et4N)3[19] were obtained by vapor diffusion of
ether into an acetonitrile solution. The structure was solved in
monoclinic space group P21/n with a ) 19.31(1) Å, b ) 64.72(4) Å,
c ) 19.49(1) Å, and â ) 119.5(1)°. Because of limited data, the
structure was refined to R1 ) 0.175 with 2θ ) 45°. The data are
sufficient to demonstrate the overall structure and certain metric features.
Reactions Monitored by 1H NMR Spectroscopy. A series of
binuclear (6-10) and mononuclear complexes (2a,b) were reacted with
cluster 14 or 15 in CD3CN, Me2SO-d6, or CD2Cl2 solution at ambient
temperature or over a temperature range. In a typical experiment, the
reaction system contained 6-17 mM cluster and an approximately equal
concentration of complex. Spectra were measured within 10-20 min
after solution preparation with a Varian AM-400B spectrometer.
Other Physical Measurements. All measurements were performed
(Bu4N)[{Ni(LO-S2N2)}Fe4S4(LS3)] ((Bu4N)[18]). To a solution of
(Bu4N)2[Fe4S4(LS3)(OTf)] (0.050 g, 0.026 mmol) in 10 mL of aceto-
nitrile was added a solution of [Ni(LO-S2N2)] (0.008 g, 0.026 mmol)
in 2 mL of acetonitrile. The mixture was stirred for 2 h and filtered
through Celite. The filtrate was concentrated and ether was layered; a
brown-black solid was obtained and washed with ether. The product
1
was obtained as 0.036 g (77%) of brown-black solid. H NMR (CD3-
CN, anion): δ 15.42, 12.78 (SCH2), 8.37 (5-H), 7.16, 6.74 (2′-H, 3′-
H), 5.04 (br, 2-H), 4.04, 3.88 (6-Me, 4-Me), 2.26 (4′-Me). Three CH2
signals and a Me signal occur as multiplets at δ ∼1.0 to 2.5.
(Et4N)3[{Ni(phma)}Fe4S4(LS3)] ((Et4N)3[19]). To a solution of
(Bu4N)2[Fe4S4(LS3)(OTf)] (0.097 g, 0.050 mmol) in 10 mL of aceto-
nitrile were added a solution of (Et4N)2[Ni(phma)]32 (0.029 g, 0.055
mmol) in 3 mL of acetonitrile and a solution of (Et4N)(BF4) (0.012 g,
1
under anaerobic conditions. H NMR spectra were measured with a
(32) Kru¨ger, H.-J.; Peng, G.; Holm, R. H. Inorg. Chem. 1991, 30, 734-743.
(33) Kru¨ger, H.-J.; Holm, R. H. Inorg. Chem. 1989, 28, 1148-1155.
(34) Schneider, J.; Hauptmann, R.; Osterloh, F.; Henkel, G. Acta Crystallogr.
1999, C55, 328-330.
(30) Brugat, N.; Polo, A.; AÄ lvarez-Larena, A.; Piniella, J. F.; Real, J. Inorg.
Chem. 1999, 38, 4829-4837.
(31) Zhou, J.; Hu, Z.; Mu¨nck, E.; Holm, R. H. J. Am. Chem. Soc. 1996, 118,
1966-1980. In a matter relevant to this work, footnote 53 in the cited
work points out that the cluster formulated as [Fe4S4(LS3)(OTf)]2- may
actually be [Fe4S4(LS3)(solv)x]- in a donor solvent. In either formulation,
the unique site is certain to be more activated toward substitution than the
site in 15. The triflate formulation is retained here.
(35) Stack, T. D. P.; Holm, R. H. J. Am. Chem. Soc. 1988, 110, 2484-2494.
(36) Ciurli, S.; Carrie´, M.; Weigel, J. A.; Carney, M. J.; Stack, T. D. P.;
Papaefthymiou, G. C.; Holm, R. H. J. Am. Chem. Soc. 1990, 112, 2654-
2664.
(37) Blessing, R. H. Acta Crystallogr. 1995, A51, 33-38.
(38) See paragraph at the end of this article for Supporting Information Available.
9
1936 J. AM. CHEM. SOC. VOL. 127, NO. 6, 2005

Bridge Formation in A-Cluster Analogue of CODH/ACS
A R T I C L E S
Scheme 1. Synthesis of Bridged Complexes with Appended FeII (4), NiII (5, 8), PdII (6, 9), and PtII (7, 10) Units from Precursor NiII Complex
3 by the Formation of Nonplanar Ni(µ2-SR)2M Rhombs
Scheme 2. Formation of Bridged NiII (12) and PtII (13) Complexes from Precursor NiII Complex 11 by Means of Ni(µ2-SR)2MII Rhombs
ring structure with M ) NiII/PdII/PtII (8-10). Preparations of
Varian AM-400B spectrometer. Electrospray mass spectra were re-
corded on a Platform II quadrupole mass spectrometer (Micromass
reactant complexes are summarized in Schemes 1 and 2.
Instruments, Danvers, MA) or on an LCT-TOF mass spectrometer
Structures of selected molecules are provided in Figures 2 and
3, together with metric parameters of coordination units.
(Micromass Instruments, Danvers, MA).
Results and Discussion
Dinuclear reactants are based on planar complex 3,26 selected
because its S-Ni-S angle of 84.2° 34 is favorable for closing
Step (iii) is ideally represented by minimal reaction 1, in
which a nickel- or other metal-bound terminal thiolate forms a
single unsupported bridge to an Fe4S4 cluster. Components of
the reaction systems are first considered, followed by a
discussion of real or potential bridging reactions themselves.
a Ni(µ2-SR)2M ring17 and also because its 5-6-5 chelate ring
1
pattern is symmetrical, a property advantageous to H NMR
examination of reaction products. This complex binds FeII, NiII,
PdII, and PtII, thus providing further examples of stable
molecules with NiII(µ2-SR)2MII bridge rhombs (Scheme 1).
Complex 4 (NiIIFeII) demonstrates the ability to bind FeII in a
tetrahedral environment that is highly distorted, primarily by
the S-Fe-S angle of 72.7(1)° which is inflicted by the S-Ni-S
bite angle of 82.1(1)° and pyramidal stereochemistry at the sulfur
atoms (Figure 2). Complexes 6 (NiIIPdII) and 7 (NiIIPtII),
obtained by the reaction of 3 with [M(PPh3)2Cl2], contain
potentially replaceable ligands at their planar PdII and PtII sites
(Figure 3). Attempts to prepare the binuclear NiIINiII complex
by an analogous reaction afforded instead green trinuclear 5,
whose linear Ni3 arrangement (Figure 2) is frequently formed
when attempting to prepare thiolate species of lower nuclearity.
Trinuclear bridged NiII-S2N2 complexes are now commonly
encountered.18,43-49 Complexes 9 (NiIIPdII) and 10 (NiIIPtII) are
readily formed by displacement of unidentate ligands from
[Fe4S4]2+ + MII-SR f [Fe4S4]2+-(µ2-SR)-MII (1)
Design of Reaction Systems. (a) Clusters. The site of
binding of the nickel thiolate moiety on the Fe4S4 portion of
the A-cluster is differentiated by protein structure. Here that
situation is simulated by the use of 3:1 site-differentated clusters
14 and 15 supported by the semirigid tridentate cavitand ligand
LS3.39 These clusters sustain regiospecific substitution reactions
at the unique site, as illustrated by generalized reaction 2, in
which the original ligand is itself a potential bridging ligand
(L′ ) SEt) or is readily displaced by a donor solvent or an
incoming ligand (L′ ) TfO-).31 Product formation is indicated
from the pronounced sensitivity of some or all of the 4-Me,
1
5-H, and 6-Me H isotropic shifts to the identity of the ligand
at the unique site.20,36,40,41 Representative examples of reaction
2 have been summarized.42
(39) Stack, T. D. P.; Weigel, J. A.; Holm, R. H. Inorg. Chem. 1990, 29, 3745-
3760.
(40) Weigel, J. A.; Holm, R. H. J. Am. Chem. Soc. 1991, 113, 4184-4191.
(41) Zhou, C.; Holm, R. H. Inorg. Chem. 1997, 36, 4066-4077.
(42) Venkateswara Rao, P.; Holm, R. H. Chem. ReV. 2004, 104, 527-559.
(43) Wei, C. H.; Dahl, L. F. Inorg. Chem. 1970, 9, 1878-1887.
(44) Barrera, H.; Suades, J.; Perucaud, M. C.; Brianso´, J. L. Polyhedron 1984,
3, 839-843.
[Fe4S4(LS3)L′]2- + Xz f [Fe4S4(LS3)X](1-)+z + (L′)- (2)
(b) Dinuclear Metal Reactants. These species contain Ni(µ2-
SR)2M bridge rhombs with potentially displaceable ligands
bound to M ) PdII/PtII (6, 7) or an M-SR group as part of a
(45) Turner, M. A.; Driessen, W. L.; Reedijk, J. Inorg. Chem. 1990, 29, 3331-
3335.
9
J. AM. CHEM. SOC. VOL. 127, NO. 6, 2005 1937

A R T I C L E S
Rao et al.
Figure 2. Structures of the NiIIFeII complex 4 (upper) and the trinuclear
centrosymmetric NiII complex 5 (lower). In this and other X-ray structural
figures, 50% probability ellipsoids and partial atom labeling schemes are
shown. Selected (mean) dimensions: for 4, Ni-N 1.989(8) Å, Ni-S1 2.177-
(3) Å, Ni-S2 2.188(2) Å, Fe-S1 2.426(3) Å, Fe-S2 2.410(3) Å, S1-
Ni-S2 82.1(1)°, S1-Fe-S2 72.7(1)°; for 5, Ni-N 1.979(4) Å, Ni1-S
2.170(2) Å, Ni2-S 2.208(1) Å, S1-Ni1-S2 81.27(5)°, S1-Ni2-S2 79.59-
(5)°.
[M(SCH2CH2PPh2)(PPh3)Cl]. The PdII complex used in the
synthesis of 9 has been reported;30 PtII complex 1 was prepared
and structurally characterized (Figure 4) as a precursor to 10.
Complex 8 (NiIINiII) could not be prepared by a similar method
but was obtained by cleavage of dinuclear [Ni2(Ph2PCH2CH2(µ2-
S))2Cl2] by 3. Less extensive experimentation with unsym-
metrical 11 as the basis complex afforded previously prepared
trinuclear 1217 and a new species, 13 (NiIIPtII, Figure 3),
obtainable by two procedures. All attempts to synthesize
dinculear complexes analogous to 8-10 from 11 did not yield
tractable materials. Reactions intended to form NiIINiII com-
plexes gave 12 instead. Members of the set 5-10 have the
common features of nonplanar NiII-(µ2-SR)2-MII bridge
rhombs folded by 107-118° along the S‚‚‚S direction and planar
coordination sites.
Figure 3. Structures of the NiII PdII complex 6 (upper), NiIINiII complex
8 (middle), and NiIIPtII complex 13 (lower). Complex 7 is isostructural with
6, and complexes 9 and 10 are isostructural with 8. Selected (mean)
dimensions: for 6, Ni-N 1.991(5) Å, Ni-S1 2.184(2) Å, Ni-S2 2.160(2)
Å, Pd-S 2.325(2) Å, Pd-Cl 2.310(2) Å, Pd-P 2.282(2) Å, S1-Ni-S2
81.87(7)°, S1-Pd-S2 75.48(6)°; for 7, Ni-N 1.989(7) Å, Ni-S1 2.190-
(2) Å, Ni-S2 2.165(3) Å, Pt-S1 2.282(3) Å, Pt-S2 2.358(2) Å, Pt-Cl
2.321(2) Å, Pt-P 2.257(2) Å, S1-Ni-S2 81.51(9)°, S1-Pt-S2 75.54-
(8)°; for 8, Ni-N 1.977(6) Å, Ni1-S 2.158(2) Å, Ni2-S1 2.229(2) Å,
Ni2-S2 2.229(2) Å, Ni2-S3 2.156(2) Å, Ni2-P 2.142(2) Å, S1-Ni1-
S2 80.32(7)°, S1-Ni2-S2 77.25(7)°, P-Ni2-S3 87.70(7)°; for 9, Ni-N
1.991(7) Å, Ni-S 2.176(3) Å, Pd-S1 2.364(2) Å, Pd-S2 2.360(2) Å, Pd-
S3 2.278(2) Å, Pd-P 2.230(2) Å, S1-Ni-S2 81.79(9)°, S1-Pd-S2 74.17-
(8)°, P-Pd-S3 86.34(8)°; for 10, Ni-N 1.981(7) Å, Ni-S 2.181(2) Å,
Pt-S1 2.364(2) Å, Pt-S2 2.354(2) Å, Pt-S3 2.283(2) Å, Pt-P 2.228(2)
Å, S1-Ni-S2 81.41(9)°, S1-Pt-S2 74.17(7)°, P-Pt-S3 86.83(8)°; for
13, Ni-N 1.85(2) Å, Ni-S 2.15(1) Å, Pt-S 2.368(4) Å, Pt-P 2.29 (1) Å,
Ni‚‚‚Pt 3.077(2) Å, S-Ni-S 84.1(2)°, S-Pt-S 74,8(1)°.
(c) Mononuclear Metal Reactants. The thiolate complex
[Ni(pdmt)(SEt)]- (2a) was reported previously.33 The corre-
sponding PdII complex 2b has been prepared in an analogous
manner by cleavage of dinuclear [Pd2(pdmt)2] with ethane-
thiolate (Scheme 3). It is planar and isostructural with
[Ni(pdmt)(SEt)]- (Figure 4). These molecules present a highly
basic alkylthiolate ligand in a sterically unimpeded position.
Attempts to prepare the corresponding PtII complex by thiolate
cleavage of [Pt2(pdmt)2]28 were unsuccessful. The dinuclear
structures proposed for the NiII and PdII complexes by our-
selves33 (Scheme 3) and others28 follow by analogy from proven
structures of dinuclear NiII complexes with five-membered
(46) 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.
(47) Golden, M. L.; Jeffery, S. P.; Miller, M. L.; Reibenspies, J. H.; Darensbourg,
M. Y. Eur. J. Inorg. Chem. 2004, 231-236.
(48) Hatlevik, O.; Blanksma, M. C.; Mathrubootham, V.; Arif, A. M.; Hegg, E.
L. J. Biol. Inorg. Chem. 2004, 9, 238-246.
(49) Golden, M. L.; Rampersad, M. V.; Reibenspies, J. H.; Darensbourg, M.
Y. Chem. Commun. 2003, 1824-1826.
9
1938 J. AM. CHEM. SOC. VOL. 127, NO. 6, 2005

Bridge Formation in A-Cluster Analogue of CODH/ACS
A R T I C L E S
Table 1. Chemical Shifts of [Fe4S4(LS3)] Clusters
δ
solvent
T (K)
SCH2
5-H
6-Me, 4-Me
ref
[Fe4S4(LS3)(SEt)]2- (15)
CD3CN
CD2Cl2
296
296
273
243
13.20
8.15
8.04
7.95
7.80
8.12
8.13
8.66
8.25
8.12
8.24
8.22
8.13
8.32
8.33
8.25
8.37
8.11
8.03
7.87
8.06
8.16
8.10
7.96
8.12
8.15
8.12
8.03
7.94
7.79
3.82, 3.69
3.87, 3.76
3.71b
3.61, 3.46
3.80, 3.65
3.85, 3.65
4.53, 4.09
3.93b
23
a
13.06
12.32
11.13
[Fe4S4(LS3)(SBut)]2-
[Fe4S4(LS3)(SPh)]2-
[{Fe4S4(LS3)}2S]4-
CD3CN
Me2SO-d6
CD3CN
CD3CN
Me2SO-d6
CD3CN
Me2SO-d6
CD2Cl2
Me2SO-d6
Me2SO-d6
CD3CN
35
36
23
296
296
296
296
296
296
296
296
296
296
296
273
243
296
296
273
243
296
296
296
296
273
243
[Fe4S4(LS3)(OTf)]2- (14)
3.84, 3.57
a
[Fe4S4(LS3)Cl]2- (16)
3.88b
3.91, 3.80
3.92b
a
a
36
36
a
[Fe4S4(LS3)(bdt)]3-
4.06, 3.46
4.08, 3.47
3.94, 3.68
4.04, 3.88
3.89, 3.71
3.75, 3.65
3.59, 3.50
3.78, 3.67
3.83, 3.69
3.71, 3.63
3.48b
3.83, 3.57
3.83, 3.70
3.84, 3.58
3.92, 3.75
3.76, 3.70
3.61, 3.45
[Fe4S4(LS3)(tdt)]3-
[{Ni(phma)}Fe4S4(LS3)]3-
[{Ni(Lo-S2N2)}Fe4S4(LS3)]-
13.32
15.42, 12.78
13.35
12.66
11.38
13.13
13.22
12.51
11.14
13.01
13.21
13.08
13.01
12.32
11.10
CD3CN
CD2Cl2
[Fe4S4(LS3)(OTf)]2-
/
a
[Ni(pdmt)(SEt)]- (20)
+ CD3CNc
CD3CN
a
a
Me2SO-d6
CD3CN
[Fe4S4(LS3)(OTf)]2-
[Pd(pdmt)(SEt)]-
/
a
a
Me2SO-d6
d
CD2Cl2
a This work. b One signal observed. c Added to CD2Cl2 solution; 3:7 v/v CD3CN/CD2Cl2. d Shifts identical to those of [Fe4S4(LS3)(SEt)]2- at 213-296
K.
Scheme 3. Synthesis of PtII Complex 1, NiII Complex 2a, and PdII
Complex 2b
useful for cluster identification in these and other reaction
systems are collected in Table 1. Results are summarized in
Scheme 4; note the substituent numbering of the LS3 ligand.
The 5-H signal in particular is very sharp and sensitive to the
1
ligand at the unique site. It is well established that H NMR
Figure 4. Structures of PtII complex 1 (upper) and PdII complex 2b (lower).
Selected dimensions: for 1, Pt-P1 2.215(4) Å, Pt-P2 2.281(4) Å, Pt-
Cl1 2.362(4) Å, Pt-S1 2.319(3) Å; for 2b, Pd-N1 2.035(3) Å, Pd-S1
2.284(1) Å, Pd-S2 2.304(1) Å, Pd-S3 2.305(1) Å, S2-Pd-S3 170.56-
(4)°, S1-Pd-S2 90.52(5)°, S1-Pd-S3 98.68(4)°.
resonances of [Fe4S4]2+ clusters are isotropically (paramagneti-
cally) shifted by dominant contact interactions arising from
thermal occupancy of an excited S ) 1 state. The isotropic
components of the chemical shifts decrease with decreasing
temperature owing to reduced population of the triplet state.53
aminodithiolate chelate rings50,51 and the mass spectrometric
observation of the dinuclear parent ion of the NiII complex.52
Reactions of Dinuclear Complexes. Reactions of clusters
Treatment of thiolate cluster 15 with 6 or 7 potentially could
result in displacement of phosphine and/or chloride and the
development of the desired Fe-(µ2-SEt)-M bridge. However,
reactions in Me2SO solutions afforded the same major product;
1
14 and 15 and complexes 6-10 were examined in situ by H
NMR spectroscopy in homogeneous solutions. Chemical shifts
(50) Colpas, G. J.; Kumar, M.; Day, R. O.; Maroney, M. J. Inorg. Chem. 1990,
29, 4779-4788.
(51) Choudhury, S. B.; Pressler, M. A.; Mirza, S. A.; Day, R. O.; Maroney, M.
J. Inorg. Chem. 1994, 33, 4831-4839.
(52) Constable, E. C.; Lewis, J.; Marquez, V. E.; Raithby, P. R. J. Chem. Soc.,
Dalton Trans. 1986, 1747-1749.
(53) Reynolds, J. G.; Laskowski, E. J.; Holm, R. H. J. Am. Chem. Soc. 1978,
100, 5315-5322.
9
J. AM. CHEM. SOC. VOL. 127, NO. 6, 2005 1939

A R T I C L E S
Rao et al.
Scheme 4. Formation of 3:1 Site-Differentiated Clusters with Four- or Five-Coordinate Unique Sites by Ligand Substitution (16, 17), Binding
of NiII-S2N2 Complexes (18, 19), or Cleavage of Dinuclear Complexes (18)a
a Cluster 16 is the major product in the reaction of 15 with 6/7. The bridging interactions in 19 are highly unsymmetrical. Note the LS3 numbering scheme
in 14; 3LS ) LS3 in 15-19 and in Scheme 5.
none of the initial cluster remained. The product spectrum is
identical to that of chloride cluster 16, whose structure has been
determined.35 In these systems, chloride replaces thiolate in
proposed reaction 3. Thiolate is fully transferred to the softer
reaction was isolated as the black Bu4N+ salt in 77% yield.
With reference to Figure 5A-C, the 1H NMR spectrum of this
material (5C) is different from that of initial cluster 14 (5A)
and displays a 5-H shift (δ 8.37), characteristic of a five-
coordinate FeS5 site as in 17 and related clusters,36 and two
SCH2 signals (δ 12.78, 15.42). The identity of the product was
established by an X-ray structure determination. The solvated
Bu4N+ salt of cluster 18 crystallizes with two crystallographi-
cally independent anions whose structures are very similar. The
overall structure of 18 is set out in Figure 6; more detailed views
of the individual clusters are provided in Figure 7. Metric
features are summarized in Table 2. The essential structural
features of clusters bound by the trigonal semirigid cavitand
ligand LS3 have been analyzed previously.39 The cluster has
the ababab conformation in which the three p-tolylthio groups
are the same side of the central benzene ring, opposite the
coordinating arms. The most prominent feature is the five-
coordinate iron site, at which [Ni(LO-S2N2)] is bridged to the
[Fe4S4]2+ core by means of nonplanar Ni(µ2-SR)2Fe rhombs with
dihedral angles of 99.0° and 100.9° between the FeS2 and mean
NiS2N2 planes. The fold along the S‚‚‚S direction positions the
nickel atom above the Fe1-S3 and Fe5-S16 core edges of the
two clusters, at the nonbonding distances of 3.16 Å from S3
and 3.34 Å from S16. The coordination geometry at the unique
iron sites is highly irregular but can be conceptualized as a
distorted square pyramid. Taking cluster 1 as an example, the
angles S3-Fe1-S1,2,5,6 occur in the range 101.6(1)-112.6-
(2)°; the two largest S-Fe-S angles, S1-Fe1-S5 ) 141.0-
(2)° and S2-Fe1-S6 ) 149.1(2)°, define the equatorial sulfur
atoms and relegate S3 to the axial position. The iron atom is
[Fe4S4(LS3)(SEt)]2- + [{Ni(LO-S2N2)}M(PPh3)Cl]+ f
[Fe4S4(LS3)Cl]2- + [{Ni(LO-S2N2)}M(PPh3)(SEt)]+ (3)
metal center rather than forming a bridge. Systems initially
containing triflate cluster 14 with complexes 8, 9, or 10 in
dichloromethane, in which the potential proximal metal site is
bound to a putative µ2-SR group in a ring structure, resulted in
the same major product 18 in each case, recognized by two
equally intense downfield signals (δ 12.78, 15.42). Additionally,
the 5-H shift (δ 8.37) does not correspond to any known cluster
in this solvent. The identity of the product was suggested by a
similarity to the spectrum of the 2:2 site-differentiated cluster
[{Ni(LO-S2N2)}2Fe4S4I2] (δ 16.76, 18.96 in CD2Cl2) obtained
from the reaction of 2 equiv of [Ni(LO-S2N2)] and 1 equiv of
[Fe4S4I4]2-, and its thiolate substitution product [{Ni(LO-S2N2)}2-
Fe4S4(Stibt)2] (δ 12.76, 15.26 in CDCl3).26 These signals arise
from the SCH2 group of complex 3, bound as a bidentate ligand
at two iron sites of the [Fe4S4]2+ core. Small amounts of 18
were also detected in the reactions of 15 with 6 or 7.
Identification of the preceding reaction product was sought
by means of reaction 4 in acetonitrile. The product of this
[Fe4S4(LS3)(OTf)]2- + [Ni(LO-S2N2)] f
[{Ni(LO-S2N2)}Fe4S4(LS3)]- + TfO- (4)
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1940 J. AM. CHEM. SOC. VOL. 127, NO. 6, 2005

Bridge Formation in A-Cluster Analogue of CODH/ACS
A R T I C L E S
Figure 6. Structure of cluster 18 showing the entire anion. The asymmetric
unit contains two inequivalent clusters with very similar structures. One
cluster is shown in a ball-and-stick presentation for clarity.
Figure 5. 1H NMR spectra of clusters 14 (A), 17 (B), 18 (C), and 19 (D).
In this and subsequent NMR figures, spectra refer to 298 K, solvents and
signal assignments are indicated, and x ) impurity.
displaced 0.62 Å in the direction of S3. Equatorial bond angles
are 65.0(2)° and 89.9(2)-98.3(2)°, with the smallest angle in
the bridging rhomb. Axial-equatorial bond angles define the
range 103.0(1)-112.6(2)°. The Fe(µ2-SR)2Ni bridge rhomb
differs from that in 4 most notably because of unsymmetrical
Fe-SR coordination. Bond lengths differ by 0.07 and 0.13 Å
in the two clusters, with the longer distances of 2.524(6) and
2.573(5) Å representing weak interactions (Figure 7). Core Fe-S
bonds opposite the two Fe-SR bonds occur in the 2.32-2.37
Å interval, compared to the mean value of 2.27(2) Å for all
other core bonds, reflecting a trans influence of the µ2-SR
ligands in the five-coordinate sites. The disposition of the two
ethyl groups on the same side of the NiS2N2 coordination plane
differentiates the SCH2 protons, accounting for two isotropically
shifted resonances. Overall, the structure of 18 is similar to those
Figure 7. Structures of the two inequivalent clusters of 18, with Fe-S
bond lengths (Å) in the bridging rhombs.
of the clusters reported by Osterloh et al.,26 but differs by binding
one complex 3 owing to its site-differentiated nature. A
preliminary structure of [{Ni(LO-S2N2)}Fe4S4I3]-, obtained with
low-quality data from a synthesis described as being of poor
reliability, has been communicated.25
The possibility of other clusters similar to 18 was pursued
by the reaction of 14 with the planar bis(amidatethiolate)
complex [Ni(phma)]2- 32
. Black (Et4N)3[19] was isolated in 87%
yield. The structure of cluster 19 (Scheme 4) has been
determined but not at a level of accuracy appropriate for a
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J. AM. CHEM. SOC. VOL. 127, NO. 6, 2005 1941

A R T I C L E S
Rao et al.
Table 2. Selected Bond Distances (Å) and Angles (deg) for [{Ni(LO-S2N2)}Fe4S4(LS3)]- and [{Fe4S4(LS3)}2(SEt)]3-
[{Ni(LO-S2N2)}Fe4S4(LS3)]- (18)
cluster 1
cluster 2
bridge
Ni-S
2.173(7)b
2.454(5)b
2.129(5)c
2.524(6)c
2.136(7)d
2.573(5)d
2.166(6)e
Fe-S
2.438(6)e
Ni-Fe
2.819(3)
2.911(3)
Ni-S-Fe
S-Ni-S
S-Fe-S
FeS2/NiS2N2
74.8(2)b
74.1(2)c
75.7(2)d
78.2(2)e
76.5(4)
65.0(3)
99.0(2)
79.4(3)
66.6(2)
100.1(2)
terminal
Fe-S(LS3)a
core
mean of 3
2.255(9)h
2.256(1)i
Fe-S
2.332(4)f
2.345(4)f
2.317(4)g
2.374(4)g
range of 10
mean of 10
range of 3
range of 3
2.243(4)-2.294(4)h
2.27(2)
2.254(4)-2.294(4)i
2.27(2)
Fe-Fe
2.780(2)-2.887(2)j
2.705(3)-2.770(2)h
2.799(2)-2.914(3)k
2.719(3)-2.769(3)i
[{Fe4S4(LS3)}2(SEt)]3- (21)
cluster 1
cluster 2
bridge
Fe-Sa
2.307(3)
119.70(11)
3.999(2)
2.316(3)
123.21(13)
4.074(2)
Fe-S-Fe
Fe‚‚‚Fe
terminal
Fe-S(LS3)a
core
mean of 6
2.252(9)h,i
2.255(9)l,m
Fe-S
4 at 2.255(8)i,k
4 at 2.283(6)i,k
4 at 2.24(1)h,j
8 at 2.31(1)h,j
4 at 2.253(8)l,n
4 at 2.29(1)l,n
4 at 2.24(1)m,o
8 at 2.315(7)m,o
4 at 2.320(3)i,k
4 at 2.319(6)l,n
Fe-Fe
range
mean of 6
range
2.677(2)-2.786(2)h,j
2.73(4)h,j
2.705(2)-2.754(2)l,n
2.73(2)l,n
2.726(2)-2.768(2)i,k
2.74(2)i,k
2.671(2)-2.756(2)m,o
2.73(3)m,o
mean of 6
a Mean values. b S5. c S6. d S20. e S21. f Fe1-S2,3. g Fe5-S17,18. h Fe2,3,4. i Fe6,7,8. j Fe1. k Fe5. l Fe10,11,12. m Fe14,15,16. n Fe9. o Fe13.
detailed description because of limited data. However, the
compound has been found to have two clusters in the asym-
metric unit with the same overall structure as 18. [Ni(phma)]2-
is coordinated at the unique iron site in a highly unsymmetrical
binding mode (Fe-SR ) 2.39(1) and 2.64(1) Å in one cluster
and 2.45(1) and 2.61(1) Å in the other). Although five-
coordinate 3:1 site-differentiated Fe4S4 clusters have been
previously isolated,20,36 18 and 19 are the first such clusters
whose structures have been determined. These structures are
related to those of [{Ni(LO-S2N2)}Fe4S4I3]- and [{Ni(LO-
S2N2)}2Fe4S4L2] (L ) I-, 2,4,6-Pri3C6H2S-) described earlier
by Osterloh et al.25,26 Core and bridge rhomb dimensions are
comparable to those reported here. Coordination at the unique
site is symmetrical in the first iodide cluster cited (Fe-SR )
2.519(8) and 2.536(9) Å) and nearly so in the second iodide
cluster (Fe-SR ) 2.464(2) and 2.533(2) Å). However, in the
thiolate cluster the sites binding the complex are essentially four-
coordinate because of one very long Fe‚‚‚SR separation in each
(2.812(5) and 2.941(5) Å). The cause of such markedly
unsymmetrical binding is not clear. In acetonitrile solution, the
inequivalent Fe-S interactions in 19 are averaged, as indicated
by a single SCH2 signal at δ 13.32 in Figure 5D. The 5-H
resonance at δ 8.25 implies FeS4 coordination at the unique
site (Table 1). The single methylene signal of 19 (averaged C2V
symmetry) is consistent with the explanation of two such signals
in 18 (limiting Cs symmetry).
rhomb and transfer of complex 3 to the cluster (8-10). It is
perhaps ironic that PdII and PtII were introduced before the fact
to stabilize the dinuclear structure, yet their complexes are as
readily cleaved under the conditions tested as is the NiIINiII
complex 8. With these results in hand, attention was directed
to mononuclear systems containing NiII or PdII thiolate com-
plexes where outcome (ii) is obviated but outcome (i) is not.
Reactions of Mononuclear Complexes. The reactions of
triflate cluster 14 with complexes 2a,b were examined in
acetonitrile, Me2SO, and dichloromethane solutions. Products
are depicted in Scheme 5. The following five reaction systems
gave equivalent results: 2a and 2b in Me2SO and acetonitrile
and 2b in dichloromethane. Outcome (i) of these systems is
1
readily conveyed by the H NMR spectrum of the equimolar
2b/14 in Me2SO, provided in Figure 8 and generalized by
thiolate transfer reaction 5. The sole cluster product is thiolate
[Fe4S4(LS3)(OTf)]2- + [M(pdmt)(SEt)]- f
[Fe4S4(LS3)(SEt)]2- + 1/2[M2(pdmt)2] + TfO- (5)
cluster 15, identified by its SCH2 (δ 13.08) and 5-H (δ 8.12)
resonances. The dinuclear PdII complex (Scheme 3) is ascer-
tained by its methylene signal (δ 4.24), identical with the
spectrum of an authentic sample. Formation of [Ni2(pdmt)2] in
other systems is evident by methylene chemical shifts (e.g., δ
3.59 and 3.91 in Me2SO). In acetonitrile, the reaction is driven
in part by the sparing solubility of the dinuclear product;
however, in Me2SO or dichloromethane, the compound is
completely soluble under the conditions used. It is implausible
In summary, reactions of dinuclear metal complexes with 14
or 15, set out in Scheme 4, result in (i) thiolate transfer from
the cluster to the reactant (6, 7) or (ii) cleavage of the bridge
9
1942 J. AM. CHEM. SOC. VOL. 127, NO. 6, 2005

Bridge Formation in A-Cluster Analogue of CODH/ACS
A R T I C L E S
Figure 8. 1H NMR spectrum of a solution initially containing equimolar cluster 14 and complex 2b in Me2SO solution. The reactants form 15 in a thiolate
transfer reaction.
Scheme 5. Reactions Based on Triflate Cluster 14: Formation of
1) and no additional signals attributable to a cluster species. At
15 by Thiolate Transfer from NiII/PdII Complexes in Acetonitrile or
all temperatures the methylene shifts do not correspond to 15.
Me2SO, Bridged Assembly 20 (Not Isolated) by Reaction with
[Ni(pdmt)(SEt)]- in Dichloromethane, and Bridged Double Cubane
21 by Reaction of Et3NH+ and [Fe4S4(LS3)(SEt)]2- in Acetonitrile
and Crystallization by Addition of Ether
We attribute these observations to the occurrence of reaction 6,
which generates bridged assembly 20 with an unsupported Ni-
(µ2-SEt)-Fe bridge (Scheme 5). Note that the SCH2 shifts of
[Fe4S4(LS3)(OTf)]2- + [Ni(pdmt)(SEt)]- f
[{Ni(pdmt)(SEt)}Fe4S4(LS3)]2- + TfO- (6)
20 and 19 (δ 13.32 in CD3CN, Figure 5D) are nearly the same.
Cluster 19 contains the Ni-(µ2-SCH2R′)-Fe fragment proposed
in 20 (but with a different R′ group). Also observed in Figure
9B are several pdmt signals which, because of signal overlap,
cannot be specifically assigned. In dichloromethane, complex
2a reacts with the solvent to form ca. 50% [Ni2(pdmt)2] (δ 3.66,
4.06) and unidentified species. The spectrum of this solution
does not contain the resonance at δ 13.35. Reactions of
terminally coordinated thiolates with chlorinated solvents have
been observed previously.26,54
The signal at δ 13.35 is not shifted when the intial mole ratio
2a:14 is 2.3 or 8.9, indicating that the chemical shift is limiting.
Under these conditions, a small amount of thiolate cluster 15
(<10% of total cluster product) is formed. As shown in Figure
9C, the system can be reversed in the form of reaction 7.
Addition of acetonitrile to afford a 3:7 v/v acetonitrile/
[{Ni(pdmt)(SEt)}Fe4S4(LS3)]2-
f
[Fe4S4(LS3)(SEt)]2- + 1/2[Ni2(pdmt)2] (7)
that, in the solvents utilized, reaction 5 proceeds by thiolate
dissociation. Consequently, thiolate transfer requires the presence
of a dinuclear intermediate or transition state of the form [Ni‚
‚‚S(Et)‚‚‚Fe], encouraging a further search for a detectable
bridged species.
The equimolar system 2a/14 in dichloromethane behaves
differently, as may be seen by reference to Figure 9A,B. The
product spectrum (9B) does not contain signals due to the
putative thiolate transfer product 15 (9A). Further, the 5-H shift
is consistent with a thiolate ligand at the unique site, and the
SCH2 signal (δ 13.35) does not correspond to any previously
encountered cluster species. The latter signal is displaced from
δ 1.70 in diamagnetic 2a, indicating that it is paramagnetically
shifted by binding to the cluster. Examination of the reaction
mixture down to 243 K reveals decreased isotropic shifts (Table
dichloromethane solution completely abolishes the signals
assigned to 20, which are replaced by those of 15 and [Ni2-
(pdmt)2]. Evidently, the NiII site is subject to attack by the donor
solvent, causing rupture of the weakened Ni-SEt bridge bond.
Complex 2a itself is stable in acetonitrile. The cause of the lack
of formation of a bridged PdII assembly is not clear but
presumably lies in the greater stability of [Pd2(pdmt)2] vs [Ni2-
(pdmt)2].
Thiolate-Bridged Fe4S4 Double Cubane. During the course
of substitution reactions of thiolate cluster 15, we observed that
reaction with Et3NH+ in acetonitrile followed by solvent
removal and crystallization of the residue from acetonitrile/ether
(54) Segal, B. M.; Hoveyda, H. R.; Holm, R. H. Inorg. Chem. 1998, 37, 3440-
3443.
9
J. AM. CHEM. SOC. VOL. 127, NO. 6, 2005 1943

A R T I C L E S
Rao et al.
Figure 10. Structure of the entire cluster 21 (upper) and the bridged Fe4S4
portion (lower). The asymmetric unit contains two inequivalent clusters
with very similar structures. One cluster is shown in a ball-and-stick
presentation for clarity.
Figure 9. 1H NMR spectra of cluster 15 (A), a solution initially containing
equimolar 14 and complex 2a (B), and solution B diluted with CD3CN
(C). Spectrum B is interpreted as bridged assembly 20; spectrum C
corresponds to 15. The pdmt signals in spectrum B may arise from the
bridged species and [Ni2(pdmt)2]; in spectrum C they are due to the dimer.
0.06 Å longer than mean values of terminal Fe-SR bond
lengths, signifying weaker interactions. These bridge parameters
serve as a guide to those in assembly 20, which as yet has not
been crystallized. In particular, a similar lengthening and
weakening of the Ni-SEt bond (2.183(1) Å)33 in 2a may be
anticipated in assembly 20.
afforded the hitherto unknown double cubane 21. The cluster
is formed by the apparent stoichiometry of reaction 8. The
Summary. Our recent investigation of NiII-(µ2-SR)-MII
bridging modes,17 which emphasizes formation of the rhomb
units NiII(µ2-SR)2MII, addresses steps (i) and (ii) in the construc-
tion of analogues of the A-cluster of CODH/ACS. This work
presents the initial exploration of possible means of achieving
step (iii), formation of an [Fe4S4]2+-(µ2-SR)-NiII bridge unit.
As such, it is intended to complement and extend our earlier
study. Within the manifold of 3:1 site-differentiated Fe4S4(LS3)
species, the results reveal access to four clusters: 18, with two
mutually supportive Fe-(µ2-SR)-NiII bridges; 19, with one
strong and one weaker bridge; 20, with one unsupported bridge
2[Fe4S4(LS3)(SEt)]2- + Et3NH+ f
[{Fe4S4(LS3)}2(SEt)]3- + EtSH + Et3N (8)
solvated Bu4N+ salt crystallizes with two inequivalent but nearly
structurally identical double cubane clusters in the asymmetric
unit. These clusters present the first structurally proven examples
of a single unsupported thiolate bridge involving an Fe4S4
cluster. The structure of one cluster is shown in Figure 10; metric
data for both clusters are presented in Table 2. Because of the
large quantity of data, most parameters are summarized in terms
of ranges or mean values. Our present interest in this cluster is
primarily structural.
Ligand conformations are aaaaaa (all substituents on the
same side of the central benzene ring) in cluster 1 and aaaaab
in cluster 2 (not shown). Individual cubanes within a cluster
can be described in terms of sets of Fe-S bond lengths, as in
prior structural analyses.42 In both clusters, mean values of bond
lengths sort into 4 short + 8 long in one cubane and 4 short +
4 intermediate + 4 long in the other. Structural distortions of
[Fe4S4]2+ cores are neither predictable nor easily rationalized
in the more than 40 structures that have been determined,42 as
is the case here. Overall, bond angles and distances are
unexceptional, leaving the bridge units as the principal structural
feature of the clusters. Bridge Fe-S-Fe angles are near 120°
and Fe-S distances are 2.31-2.32 Å, resulting in Fe-Fe
separations of 4.00 and 4.07 Å. Bridge distances are 0.05-
1
postulated from H NMR spectra; and double cubane 21, with
one unsupported bridge. Previously prepared double cubanes
are sulfide- or selenide-bridged,23,55-57 as exemplified by
{[Fe4S4(LS3)]2S}.4- The higher negative charge and basicity
of the bridge atoms are more conducive to bridge formation
than those of thiolate. The stability of cluster 18 is indicated
by its formation via an unexpected cleavage reaction of binuclear
complexes (6-10), several with MII components introduced to
(55) Stack, T. D. P.; Carney, M. J.; Holm, R. H. J. Am. Chem. Soc. 1989, 111,
1670-1676.
(56) Challen, P. R.; Koo, S. M.; Dunham, W. R.; Coucouvanis, D. J. Am. Chem.
Soc. 1990, 112, 2455-2456.
(57) Huang, J.; Mukerjee, S.; Segal, B. M.; Akashi, H.; Zhou, J.; Holm, R. H.
J. Am. Chem. Soc. 1997, 119, 8662-8674.
(58) Nicolet, Y.; Lemon, B. J.; Fontecilla-Camps, J. C.; Peters, J. W. Trends
Biochem. Sci. 2000, 25, 138-143.
(59) Peters, J. W.; Lanzilotta, W. N.; Lemon, B. J.; Seefeldt, L. C. Science 1998,
282, 1853-1858.
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1944 J. AM. CHEM. SOC. VOL. 127, NO. 6, 2005

Bridge Formation in A-Cluster Analogue of CODH/ACS
A R T I C L E S
retard MII-SR bond cleavage. None of these clusters contain a
binuclear fragment with NiII atoms as simulators of distal and
proximal sites.
Acknowledgment. This research was supported by NIH Grant
GM 28856. We thank Drs. C. Chiou and R. Panda for
experimental assistance and Dr. Chiou for the initial preparation
of cluster 19.
Overall, this work and other reports that precede it25,26 make
it evident that two intramolecular bridges of the desired type
are attainable using a cis-planar NiII-S2N2 complex, and that a
single unsupported bridge is achievable but less robust. Protein
Supporting Information Available: Tables of crystallo-
graphic data for mononuclear and binuclear complexes and
clusters (S1), bond distances and angles of complexes 4-7 (S2),
and bond distances and angles of [{Ni(LO-S2N2)}M(SCH2CH2-
PPh2)]+ (S3) (PDF); X-ray crystallographic files for the 12
compounds in Table S1 (CIF). This material is available free
of charge via the Internet at http://pubs.acs.org.
folding may contribute to the stabilization of the [Fe4S4]2+
-
(µ2-SCys)-NiII interaction in CODH/ACS. Further approaches
to the A-cluster may require a covalent link between the Fe4S4
and nickel-containing units in order to provide a juxtaposition
of these two units favorable to bridge formation and stability.
Finally, the bridge type realized in 21 is relevant to the Fe-
(µ2-SR)-Fe interaction that connects an Fe4S4 cluster to the
dinuclear H-cluster in iron hydrogenases.58,59
JA040222N
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J. AM. CHEM. SOC. VOL. 127, NO. 6, 2005 1945