Homonuclear dinickel complexes: Structural mimics for the dinickel subsite of the A-cluster of acetyl-CoA synthase

Article abstract of DOI:10.1016/j.inoche.2004.11.026

[Ni(ema)(μ-S,S′)Ni(dppp)] (1) and [Ni(ema)(μ-S,S′) Ni(dppe)] (2) have been prepared as synthetic structural analogues of the Ni-Ni subsite of the A-cluster of the enzyme acetyl-CoA synthase by reaction of [Ni(ema)]^2-, H₄ema is N,N′-ethylenebis(2- mercaptoacetamide), with [NiCl₂(diphos)], diphos is 1,2-bis(diphenylphosphino)propane (dppp) or 1,2-bis(diphenylphosphino)ethane (dppe). A similar reaction with 1,2-bis(diethylphosphino)ethane did not give the dinuclear product but the trinuclear complex [NEt₄] ₂[Ni{Ni(ema)(μ-S,S′)}₂] (3). Complexes 1 and 3 have been crystallographically characterised.

Full text of DOI:10.1016/j.inoche.2004.11.026

Inorganic Chemistry Communications 8 (2005) 170–173
www.elsevier.com/locate/inoche
Homonuclear dinickel complexes: structural mimics for the
dinickel subsite of the A-cluster of acetyl-CoA synthase
*
ˆ
Samantha E. Duff, J. Elaine Barclay, Sian C. Davies, David J. Evans
Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, UK
Received 18 October 2004; accepted 27 October 2004
Abstract
[Ni(ema)(l-S,S0)Ni(dppp)] (1) and [Ni(ema)(l-S,S0)Ni(dppe)] (2) have been prepared as synthetic structural analogues of the Ni–
Ni subsite of the A-cluster of the enzyme acetyl-CoA synthase by reaction of [Ni(ema)]2ꢀ, H4ema is N,N0-ethylenebis(2-mercaptoac-
etamide), with [NiCl2(diphos)], diphos is 1,2-bis(diphenylphosphino)propane (dppp) or 1,2-bis(diphenylphosphino)ethane (dppe).
A similar reaction with 1,2-bis(diethylphosphino)ethane did not give the dinuclear product but the trinuclear complex [NEt4]2[Ni
{Ni(ema)(l-S,S0)}2] (3). Complexes 1 and 3 have been crystallographically characterised.
Ó 2004 Elsevier B.V. All rights reserved.
Keywords: Nickel complexes; Acetyl-CoA synthase; Bioinorganic chemistry
The nickel enzyme acetyl-CoA synthase (ACS) cataly-
ses the synthesis of acetyl-CoA by the non-redox conden-
sation of a methyl group, a carbonyl group and an
organic thiol. The reaction parallels the industrially
important Reppe Process for the synthesis of acetic acid,
both apparently involving metal–carbonyl, methyl–metal
and acyl–metal intermediates [1]. Protein crystallography
of the nickel enzyme carbon monoxide dehydrogenase/
acetyl-CoA synthase from Moorella thermoacetica (for-
merly Clostridium thermoaceticum) shows the active site
of the A-cluster of ACS to comprise an Fe4S4-cluster
bridged through cysteinyl-thiolate sulfur to a proximal
metal that is then linked to a distal nickel(II) atom in
an N2S2 coordination environment [2,3] (Fig. 1). The
N2S2 coordination is provided for by a deprotonated
Cys–Gly–Cys sequence of the protein. The proximal me-
tal was initially determined to be tetrahedral copper(I)
[2]. A later study identified the proximal metal as
square-planar nickel(II) in an open protein conformation
and as tetrahedral zinc(II) in a closed conformation of the
protein [3]. ACS from Carboxydothermus hydrogenofor-
mans also contains an {Fe4S4}–Ni–Ni assembly [4] and
X-ray absorption spectroscopy has established the pres-
ence of a similar unit in A-cluster of the acetyl-CoA
decarbonylase/synthase complex of Methanosarcina ther-
mophila [5]. The consensus now is that active A-cluster
possesses a proximal nickel atom but that this atom is la-
bile and under certain conditions may be replaced by cop-
per or zinc to give inactive enzyme [6]. Here we report
routes to structural analogues of the dinickel subsite of
the ACS A-cluster. Concurrent with our work a similar
approach has been taken by others to prepare related
complexes
[7,8]
including
[Ni(CysGlyCys)(l-
S,S0)Ni(dppe)] [9], although the crystal structure of this
complex was not reported.
Reaction of one equivalent of [NEt4]2[Ni(ema)], H4
ema is N,N0-ethylenebis(2-mercaptoacetamide), with
one equivalent of [NiCl2(diphos)], diphos is 1,2-
bis(diphenylphosphino)propane (dppp) or 1,2-bis
(diphenylphosphino)ethane (dppe), in acetonitrile gave
*
Corresponding author. Tel.: +44 1603 450706; fax: +44 1603
450018.
E-mail address: dave.evans@bbsrc.ac.uk (D.J. Evans).
1387-7003/$ - see front matter Ó 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.inoche.2004.11.026

S.E. Duff et al. / Inorganic Chemistry Communications 8 (2005) 170–173
171
The crystal structure of 1 (Fig. 2) shows that each
nickel is slightly distorted square planar, with one nickel
(Ni(1)) ligated by the two phosphorus atoms from the
dppp ligand and the two sulfur atoms of the ema ligand
and the other nickel (Ni(2)) ligated by the two nitrogen
and two sulfur atoms of the ema ligand. The dppp li-
˚
gated nickel lies 0.0035(5) A from the P2N2 plane and
˚
the ema ligated nickel lies 0.1534(6) A from the N2S2
plane. The Ni–S bond distances within the chelate ring
˚
Fig. 1. The A-cluster of acetyl-CoA synthase.
(2.12 A) are slightly shorter and the bridging distances
the dinuclear nickel(II)–nickel(II) complexes [Ni(ema)
(l-S,S0)Ni(dppp)] (1) and [Ni(ema)(l-S,S0)Ni(dppe)]
(2), respectively, in good yield. The blue-green com-
˚
(2.28 A) slightly longer than those observed (2.14–2.19
˚
and 2.19–2.24 A, respectively) for other synthetic
sulfur-bridged dinickel complexes such as [Ni(L)(l-
S,S0)Ni(dppe)](PF6)2 (L = N,N0-diethyl-3,7-diazanon-
ane-1,9-dithiolato(2-)) [7] and [Ni(L1)(l-S,S0)Ni(dppe)]
(L1 = N-(2-mercaptopropyl)-N0-(20-mercaptoethyl)gly-
cinamide(4-)) [8]. Other angles and bond lengths about
1
2
plexes 1 and 2 have been characterised and the crystal
3
structure of 1 Æ Et2O determined.
Reaction of
[NEt4]2[Ni(ema)] with [NiCl2(depe)], where depe is the
alkylphosphine 1,2-bis(diethylphosphinoethane), in ace-
tonitrile after one hour reflux gave the black trinuclear
complex [NEt4]2[Ni{Ni(ema)(l-S,S0)}2] (3) as the only
isolable product in 38% yield. Complex (3) has been
obtained previously [10] but here the crystal structure
˚
the nickel atoms and the Niꢁ ꢁ ꢁNi distance (2.6897(8) A)
are similar to those reported for related ‘‘Ni(l-
S)2NiN2’’ structures [8]. The geometric parameters
about the nickel atoms for complex 1 (S–Ni(1)–S,
80.93(3)°; S–Ni(2)–S, 88.47(3)°; dihedral angle,
105.52(2)°) resemble those reported for the A-cluster
of ACS (S–Nid–S, 87°; S–Nip–S, 87°; dihedral angle,
138°): Ni(1) and Ni(2) mimic the A-cluster distal nickel,
Nid, and proximal nickel, Nip, respectively.
4
is reported for the first time.
1
Synthetic procedure [Ni(ema)(l-S,S0)Ni(dppp)] (1). Under a
dinitrogen atmosphere [NiCl2(dppe)] (0.54 g, 1 mmol) and [NEt4]2
[Ni(ema)] (0.52 g, 1 mmol) were dissolved in acetonitrile (10 ml) and
stirred for 20 min. Diethyl ether (5 ml) was added dropwise. After
standing for 24 h the product was collected (0.73 g, 64%). [Ni(ema)(l-
S,S0)Ni(dppe)] (2) was prepared by a similar procedure on a 0.5 mmol
scale (0.27 g, 75%).
The spectroscopic properties of 1 and 2 are as ex-
pected for diamagnetic square-planar nickel(II) com-
plexes; no epr signal is observed. The optical spectrum
of 3 shows two absorbances at 413 and 590 nm different
to those previously reported for this complex (which we
suggest were misassigned), but very similar to those
observed (423 and 608 nm) for the related trinuclear
complex bis[Ni(II)–N,N0-ethylenebis(3-mercaptopropi-
onamide)]Ni(II) [10]. The cyclic voltammogram of 1 in
dichloromethane shows a reversible one electron process
at E1/2 = ꢀ0.42 V (vs. SCE) assigned to a NiII|NiI cou-
ple. A second feature at Epc = ꢀ1.39 V (vs. SCE) may
be assigned to an irreversible reduction NiI|Ni0 or an
irreversible NiII|NiI couple at the other nickel site.
The crystal structure of 3 Æ 2H2O (the water is adven-
titious) confirms the predicted [10] trinuclear arrange-
ment of nickel atoms in this complex (Fig. 3). The
central nickel atom in the complex lies on a centre of
symmetry. Each nickel atom is square planar coordi-
nated, the central one to four sulfur atoms and the outer
two to two sulfur atoms and two nitrogen atoms; these
2
(1): Anal. Calc. C33H34N2O2P2S2Ni2 requires: C, 54.0; H, 4.7; N,
3.8. Found: C, 54.6; H, 5.0; N, 4.3%. IR (cmꢀ1, KBr): m = 1561 (C@O);
k
max/nm (MeCN) 470 sh. (e/dm3 molꢀ1 cmꢀ1 990), 637 (1330); dH
(CD2Cl2; standard SiMe4) 7.3–8.2 (20H, C6H5), 3.50 (2H, –SCH2
(CO)), 3.35 (2H, –SCH2(CO)), 3.10 (2H, –PCH2CH2), 2.30 (4H, –
NCH2), 1.90 (4H, –PCH2); dP (CD2Cl2; standard H3PO4) 31.06; mass
spectrum m/z 733 ({M + H}+, 100%). [Ni(ema)(l-S,S0)Ni(dppe)] (2):
IR (cmꢀ1
, KBr): m = 1564 (C@O); kmax/nm (MeCN) 282 (e/
dm3 molꢀ1 cmꢀ1 17,560), 472 (896), 623 (1090); dH (CD2Cl2; standard
SiMe4) 7.3–8.2 (20H, C6H5), 3.32 (4H, –SCH2C(O)), 1.80–2.40 (8H,
–NCH2 and –PCH2); dP (CD2Cl2; standard H3PO4) 55.6; mass
spectrum m/z 719 ({M + H}+, 100%).
3
Crystal data for [Ni(ema)(l-S,S0)Ni(dppp)] Æ Et2O (1) Æ Et2O:
C33H34N2Ni2O2P2S2, C4H10O, M = 808.2, orthorhombic, space group
Pcab (equiv. to Pbca, no. 61), a = 16.557(3), b = 16.799(8),
3
c = 26.931(5) A, V = 7491(4) A , Z = 8, Dc = 1.43 mg/m ; data
3
˚
˚
collection method: CAD4 scintillation counter, x scans at T = 123(2)
K, k = 0.71073 A; F(0 0 0) = 3376, l = 1.240 mmꢀ1
, R1/wR2
˚
(final) = 0.039/0.078, R1/wR2 (all data) = 0.073/0.094, goodness-of-fit
on F2 = 1.040.
4
[NEt4]2[Ni{Ni(ema)(l-S,S0)}2] (3): IR (cmꢀ1, KBr): m = 1560
(C@O);
k
max/nm (MeCN) 249 (e/dm3 molꢀ1 cmꢀ1 21,815), 287
˚
outer Ni atoms lie 0.1916(4) A from the plane displaced
(15,580), 339 (6850), 413 (3399), 590 (1965); Mass spectrum: m/z 585
({Mꢀ}, 42%), 292 ({M–H}2ꢀ, 100%). Crystal data for [NEt4]2[Ni
{Ni(ema)(l-S,S0)}2] Æ 2(H2O) (3) Æ 2(H2O): C12H16N4Ni3O4S4,
away from the central nickel. The angle between the
normals to the two planes is 107.0°. Bond dimensions
within the ema ligands are comparable to those in com-
ꢀ
2(C8H20N1), 2(H2O1), M = 881.2; triclinic, space group P1 (no. 2),
˚
˚
a = 8.9446(3), b = 9.5103(3), c = 13.0739(3) A, a = 78.310(2)°,
plex 1. The Niꢁ ꢁ ꢁNi distance in 3 is 2.6668(2) A, shorter
3
˚
b = 73.178(2)°, c = 65.382(2)°, V = 963.48(5) A , Z = 1, Dc = 1.52 mg/
0
˚
than that found, 2.9947(2) A, in related bis[nickel-N,N -
ethylenebis(3-mercaptopropionamide)]nickel [10]. The
geometric parameters about the terminal nickel atoms
in complex 3 are again similar to those reported for
m3; data collection method: CCD rotation images, thick slices, at
T = 173(2) K, k = 0.71073 A; F(000) = 466, l = 1.714 mmꢀ1, R1/
˚
wR2 = 0.022/0.052 for all data, R1/wR2 = 0.021/0.052 for 3203 observed
data, goodness-of-fit on F2 = 1.05.

172
S.E. Duff et al. / Inorganic Chemistry Communications 8 (2005) 170–173
C114
C113
C115
C112
O2
C1
C111
C116
C122
C2
N3
S1
C12
P1
C126
C4
C5
C22
Ni2
Ni1
P2
C21
C212
S2
N6
C7
C216
C226
C221
C8
O7
C222
C225
C223
C224
Fig. 2. ORTEP view of the molecule [Ni(ema)(l-S,S0)Ni(dppp)] (1). Thermal ellipsoids for non-hydrogen atoms are drawn at the 50% probability
˚
level. Selected interatomic distances (A) and angles (°): Ni(1)–P(1) 2.1893(8), Ni(1)–P(2) 2.1893(9), Ni(1)–S(1) 2.2813(9), Ni(1)–S(2) 2.2810(8), Ni(2)–
N(3) 1.838(2), Ni(2)–N(6) 1.823(2), Ni(2)–S(1) 2.1228(8), Ni(2)–S(2) 2.1218(12), Ni(1)ꢁ ꢁ ꢁNi(2) 2.6897(8) and P(1)–Ni(1)–P(2) 92.40(3), P(1)–Ni(1)–
S(1) 92.68(3), P(2)–Ni(1)–S(2) 94.01(3), P(1)–Ni(1)–S(2) 173.46(3), P(2)–Ni(1)–S(1) 174.83(3), S(1)–Ni(1)–S(2) 88.47(3), N(3)–Ni(2)–N(6) 86.51(11),
N(3)–Ni(2)–S(1) 91.88(8), N(6)–Ni(2)–S(1)172.49(8), N(3)–Ni(2)–S(2) 169.52(8), N(6)–Ni(2)–S(2) 91.78(8), S(1)–Ni(2)–S(2) 88.47(3), Ni(1)–S(1)–
Ni(2) 75.19(3), Ni(1)–S(2)–Ni(2) 75.21(3).
the A-cluster of ACS and the central square-planar nickel
atom models Nip of the A-cluster.
In summary, we have prepared homonuclear di- and
tri-nickel complexes as synthetic structural analogues of
the Ni–Ni subsite of the A-cluster of the enzyme acetyl-
CoA synthase. Now we are addressing their reactivity
by, for example, studying their interaction with carbon
monoxide.
Acknowledgements
The Biotechnology and Biological Sciences Research
Council, UK funded this work. The John Innes Founda-
Fig. 3. ORTEP of the dianion [Ni{Ni(ema)(l-S,S0)}2]2ꢀ (3). Thermal
ellipsoids for non-hydrogen atoms are drawn at the 50% probability
˚
tion is thanked for a studentship (S.E.D.). Dr. Lionel
Hill, JIC Metabolite Service is thanked for mass spec-
trometry and Dr. Xiaoming Liu, Department of Biolog-
ical Chemistry, JIC, for electrochemical measurements.
Dr. Peter B. Hitchcock, Department of Chemistry, Uni-
versity of Sussex is acknowledged for collection of the
X-ray diffraction data for complex 3.
level. Selected interatomic distances (A) and angles (°): Ni(1)–S(1)
2.2491(4), Ni(1)–S(2) 2.2324(4), Ni(2)–S(1) 2.1479(4), Ni(2)–S(2)
2.1480(4), Ni(2)–N(1) 1.8445(14), Ni(2)–N(2) 1.8380(14), Ni(1)ꢁ ꢁ ꢁNi(2)
2.6668(2) and S(2)–Ni(1)–S(1) 85.012(15), S(1)–Ni(1)–S(2_2)
94.988(15), S(1)–Ni(2)–S(2) 89.64(2), N(1)–Ni(2)–S(1) 91.03(5), N(2)–
Ni(2)–S(1) 169.88(5), N(1)–Ni(2)–S(2) 167.73(5), N(2)–Ni(2)–S(2)
90.73(5), N(2)–Ni(2)–N(1) 86.49(6), Ni(2)–S(1)–Ni(1) 74.633(14),
Ni(2)–S(2)–Ni(1) 74.979(13).

S.E. Duff et al. / Inorganic Chemistry Communications 8 (2005) 170–173
173
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