A dinuclear nickel complex modeling of the Nid(ii)-Ni p(i) state of the active site of acetyl CoA synthase

Article abstract of DOI:10.1039/b924915j

The dinuclear Ni(ii)-Ni(i) complex Ni^II(dadt^Et) Ni^I(SDmp)(PPh₃) was synthesized as a Ni(ii) _d-Ni(i)_p model of the A-cluster in acetyl CoA synthase. This complex was reacted with Co(dmgBF

Full text of DOI:10.1039/b924915j

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Tatsumi, Matsumoto et al.
A dinuclear nickel complex modeling
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Ribbe, Hu et al.
Ikariya and Kuwata
Dual functions of NifEN: insights into
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A dinuclear nickel complex modeling of the Nid(II)-Nip(I) state of the active
site of acetyl CoA synthase†
Tsuyoshi Matsumoto,* Mikinao Ito, Mai Kotera and Kazuyuki Tatsumi*
Received 26th November 2009, Accepted 7th January 2010
First published as an Advance Article on the web 19th January 2010
DOI: 10.1039/b924915j
The dinuclear Ni(II)-Ni(I) complex NiII(dadtEt)NiI(SDmp)-
(PPh3) was synthesized as a Ni(II)d–Ni(I)p model of the A-
cluster in acetyl CoA synthase. This complex was reacted
with Co(dmgBF2)2(Me)(Py) and KSDmp successively to
afford Ni(dadtEt)Ni(Me)(SDmp), which further reacts with
CO to afford the acetylthioester CH3C(O)SDmp via reductive
elimination.
which serve as structural and functional models of the NidII-Nip
0
and NidII-NipII centers of ACS.6 For instance, we have reported that
NiII(dadtEt)Ni0(cod) (cod = cyclooctadiene) reacts with methyl-
cobaloxime Co(dmgBF2)2(Me)(Py)7 (dmgBF2 = difluoroboryl-
dimethylglyoximate) and KSDmp (Dmp = 2,6-dimesitylphenyl)
successively to afford NiII(dadtEt)NiII(Me)(SDmp) (1), which
further reacts with CO to generate the acetyl CoA analog,
CH3C(O)SDmp, via reductive elimination.6a
In order to expand the scope of our study of A-cluster models,
we have examined a system at the NiII-NiI reduction level, and
this paper describes the synthesis of NiII(dadtEt)NiI(SDmp)(PPh3)
and its reaction with methylcobaloxime. While a variety of
A-cluster model complexes have been reported,6,8 dinuclear
Ni(II)–Ni(I) models remain very scarce. Schro¨der et al. de-
tected formation of [NiII(dadtEt)NiI(dppe)]+ by EPR upon
electrochemical reduction of [NiII(dadtEt)NiII(dppe)]2+,8a while
Mascharak et al. have prepared NiII–NiI complexes in situ, e. g.,
[Et4N][Ni(PhPepS)Ni(dppe)] (PhPepS = N,N¢-Phenylenebis(o-
mercaptobenzamide)), by chemical reduction of the correspond-
ing NiII-NiII complexes.8e,8h However, the structures and reactions
of these dinuclear NiII-NiI complexes have not been reported.
Our isolation of a NiI thiolate complex, NiI(PPh3)(SDmp)
Acetyl-CoA-synthase/CO-dehydrogenase (ACS/CODH) is a
novel bifunctional metalloenzyme, carrying out the important
function of fixing CO and CO2 in the global carbon cycle.1 The
enzyme produces acetyl-CoA, which is an acetylthioester, from
CO, CoA, and a methyl moiety derived from a corrinoid-iron-
sulfur protein. The active site of ACS, denoted as the A-cluster, is
composed of a redox-active [Fe4S4] cluster and a dinuclear Nid–
Nip unit. As shown in Fig. 1, the two nickel atoms designated as
Nid and Nip occupy distal and proximal positions to the [Fe4S4]
cluster, respectively.2,3
(2),9 opened a route to synthesize a NidII-Nip model of the A-
I
cluster using 2 as the Ni(I) building block. The reaction of 2 with
Ni(dadtEt) generated NiII(dadtEt)NiI(SDmp)(PPh3) (3) in 72% yield
(Scheme 1), and the molecular structure was determined by X-ray
I
analysis.‡ As shown in Fig. 2, the Nip site (Ni(2)) of 3 assumes
Fig. 1 Schematic view of the ACS active site (A-cluster).
a distorted tetrahedral geometry, where the S(3)–Ni(2)–P bond
angle is large, 134.62(4)◦. This may be partly due to the steric bulk
of SDmp. Another salient feature of the dinuclear structure is a
smaller folding angle of the Ni2S2 quadrangle (98.89◦), relative
to those of the related Ni(II)-Ni(II) complexes, Ni(dadtEt)NiL2
(103.5–119.4◦).6,8a,8f
The oxidized form of the A-cluster (Aox) has been formulated
as {NidII-NipII-[Fe4S4]2+}. However, this state is inactive and
requires reduction to promote the methyl group transfer from
methylcobalamin. One possible mechanism is based on an active
state generated by a two-electron reduction of Aox, and the electron
configuration of this reduced form has been proposed by Lindahl
et al. as either {NidII-Nip -[Fe4S4]2+} or {NidII-Nip -[Fe4S4]1+}.4 On
0
I
the other hand, Ragsdale has proposed an alternative mecha-
nism that utilizes a one-electron-reduced active state, {NidII-Nip -
I
[Fe4S4]2+}.1c,5 Recently, we reported the synthesis and some reac-
tions of the dinuclear NiII(dadtEt)-Ni0 and NiII(dadtEt)-NiII com-
plexes (dadtEt = N,N¢-diethyl-3,7- diazanonane-1,9-dithiolate),
Scheme 1 Synthesis of NiII(dadtEt)NiI(SDmp)(PPh3) (3).
Research Center for Materials Science, and Department of Chemistry, Grad-
uate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya,
464-8602, Japan. E-mail: i45100a@nucc.cc.nagoya-u.ac.jp; Fax: +81 52 789
2943; Tel: +81 52 789 2474
† Electronic supplementary information (ESI) available: Experimental
details, spectroscopic and X-ray data and cif file for 3. CCDC reference
number 737907. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/b924915j
The magnetic moment of 3 was measured over a 12–300 K
range. The observed value of 2.21–2.47 mB is consistent with the
expected spin state S = 0 at NidII (Ni(1)) and S = 1/2 at NipI (Ni(2)).
The X-band EPR spectrum in toluene displays a broad isotropic
signal at 297 K (giso = 2.20) and a rhombic spectrum at 77 K
This journal is
The Royal Society of Chemistry 2010
Dalton Trans., 2010, 39, 2995–2997 | 2995
©

signals of g = 2.08, 2.07, 2.03. The spectral disparity between 3
and these reduced states of ACS indicates that the coordination
I
geometries of the ACS Nip sites may be somewhat different from
that of 3.10,12
The cyclic voltammogram of 3 in THF shows irreversible oxida-
I
II
tion and reduction waves at Epa = -0.73 V (NidII-Nip → NidII-Nip
)
and Epc = -1.68 V (NidII-Nip → NidII-Nip ) (vs SCE, see ESI†),13
which are negatively shifted from the corresponding reduction
potentials of [NiII(dadtEt)NiII(dppe)](PF6)2, E1/2 = -0.47 V for the
NiII-NiII/NiII-NiI redox couple and Epc = -1.22 V for the reduction
of NiII-NiI to NiII-Ni0 (vs SCE), respectively,8a probably because
the thiolate DmpS- is a stronger electron donor than the phosphine
chelate dppe.8i
The reaction of the dinuclear NiII-NiI model complex 3 and
methylcobaloxime was investigated to examine the significance
of the NidII-Nip state in the function of ACS. When complex
I
0
I
3 was mixed with CoIII(dmgBF2)2(Me)(Py) in a 1 : 1 ratio and
charged with CO gas, the acetylthioester CH3C(O)SDmp was
obtained in 43% yield, based on the methylcobaloxime, with
concomitant formation of Ni0(CO)4 and NiII(dadtEt). The yield
of the acetylthioester was improved to 90% when two equiv of
3 were allowed to react, whereas further significant improvement
was not found from a three equiv addition. Furthermore, a similar
2 : 1 reaction without addition of CO resulted in the formation of
NiII(dadtEt)NiII(Me)(SDmp) (1) in 34% yield.14 These results show
that the reaction of 3 and CoIII(dmgBF2)2(Me)(Py) proceeds in a
2 : 1 ratio. Formally one equiv of 3 accepts the methyl group from
the methylcobaloxime to form 1 and cobaloxime in the CoII state,
while the second equiv of 3 provides one electron to the CoII site
of the cobaloxime, affording a dinuclear NiII-NiII cation and an
unidentified [CoI(dmgBF2)2(Py)]- anion. A similar 2 : 1 reaction of
mononuclear Ni(I) complex and methylcobaloxime was previously
reported by Riordan and co-workers, and the reaction mechanism
was investigated by kinetic study.7,15
Fig. 2 ORTEP drawing of Ni(dadtEt)Ni(SDmp)(PPh3) (3). Thermal
ellipsoids are shown at 40% probability. Selected bond distances
˚
(A) and angles (deg); Ni(1)–S(1) 2.1925(12), Ni(1)–S(2) 2.1848(12),
Ni(2)–S(1) 2.3529(12), Ni(2)–S(2) 2.3995(13), Ni(2)–S(3) 2.2273(12),
Ni(2)–P 2.2309(12), S(1)–Ni(1)–S(2) 82.96(4), S(1)–Ni(2)–S(2) 75.18(4),
S(1)–Ni(2)–S(3) 110.51(4), S(1)–Ni(2)–P 108.07(4), S(2)–Ni(2)–S(3)
111.66(4), S(2)–Ni(2)–P 100.45(4), S(3)–Ni(2)–P 134.62(4).
(g1 ª 2.62, g2 ª 2.12, g3 ª 2.00), as shown in Fig. 3. No hyperfine
splitting from the 31P nucleus was observed in the EPR spectrum.
While the g values of 3 compare well with those of the tetrahedral
NiI complex [PhTttBu]Ni(CO) (g = 2.64, 2.02, and 1.95; PhTttBu
=
phenyltris((tert-butylthio)methyl)borate),10 they are dissimilar to
those of a NiII-NiI complex, the formula of which was reported
to be [NiII(dadtEt)NiI(dppe)]+ (g = 2.158, 2.050, 2.040).8a The
“semireduced” A-cluster in the {NidII-Nip -[Fe4S4]2+} state was
I
formed via one-electron reduction of Aox, which exhibits an EPR
spectrum with gꢀ = 2.10, g• = 2.03.4e On the other hand, the EPR
I
spectrum of the Ared-CO state of ACS, {NidII-Nip (CO)-[Fe4S4]2+},
As we have reported earlier, 1 reacts with CO to afford the
thioester and a NiII-Ni0 species or [Ni0(CO)4 + NiII(dadtEt)] via
reductive elimination. Thus, according to our model study, the
methyl group transfer from methylcobaloxime occurs either to the
dinuclear NiII(dadtEt)-Ni0 or NiII(dadtEt)-NiI complex, indicating
that methylcobalamin could also react with the ACS active site
to produce acetyl-CoA regardless of the oxidation state of Nip.
generated by reduction of Aox under a CO atmosphere,11 shows
For {NidII-Nip -[Fe4S4]1+},4e methylcobalamin could react with
I
the Nip(I) site to form a NipII-Me species and cobalamin in the
formal CoII state, which then could accept one electron from
the reduced [Fe4S4]1+ cluster to be converted into the CoI state.
In our model reaction shown in Scheme 2, the electron that
reduces the cobaloxime from CoII to CoI is supplied by the
second equiv of 3. It is noteworthy that the reaction of the
methylcobaloxime with the dinuclear NiII-NiI complex 3 is consid-
erably faster than that with the corresponding NiII-Ni0 complex
NiII(dadtEt)Ni0(cod). Although the kinetic studies have not been
established, the reaction of 3 with CoIII(dmgBF2)2(Me)(Py) has
completed within 1 h at -40 ◦C while that of NiII(dadtEt)Ni0(cod)
and CoIII(dmgBF2)2(Me)(Py) requires 37 h at -30 ◦C. This result
I
might suggest the significance of the {NidII-Nip -[Fe4S4]1+} state
in the catalytic cycle of ACS. However, in our model systems,
acetylthioester formation from the reaction of 1 with CO is
accompanied by the formation of a NiII-Ni0 species. Further
modelling studies using dinuclear nickel complexes carrying a
Fig. 3 X-Band EPR spectrum of Ni(dadtEt)Ni(SDmp)(PPh3) (3); (a) at
297 K in toluene; (b) at 77 K in frozen toluene.
2996 | Dalton Trans., 2010, 39, 2995–2997
This journal is
The Royal Society of Chemistry 2010
©

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Scheme 2 The reaction of 3 with Co(dmgBF2)2(Me)(Py) and CO.
[Fe4S4] cluster are needed for a better understanding of the
function of ACS.
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Acknowledgements
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Dalton Trans., 2009, 4359.
This research was financially supported by Grant-in-Aids for
Scientific Research (Nos. 18GS0207 and 18065013) from the
Ministry of Education, Culture, Sports, Science, and Technology,
Japan, and the Global COE program (B08) from MEXT, Japan.
We are grateful to Prof. Roger E. Cramer for discussions and
careful reading of the manuscript.
Notes and references
‡ Crystal data of 3. The crystal contains 3 and a toluene molecule in
the asymmetric unit. The single crystal was mounted on a loop using oil
(CryoLoop, Immersion Oil type B: Code 1248, Hampton Laboratories,
Inc.). Diffraction data was collected at -100 ◦C under a cold nitrogen
stream on a Rigaku AFC8 equipped with a Saturn 70 CCD area
detector, equipped with a graphite monochromatized Mo-Ka source (l =
9 M. Ito, T. Matsumoto and K. Tatsumi, Inorg. Chem., 2009, 48, 2215.
10 J. L. Craft, B. S. Mandimutsira, K. Fujita, C. G. Riordan and T. C.
Brunold, Inorg. Chem., 2003, 42, 859.
˚
0.71070 A). Data were collected on 1200 oscillation images with an
11 (a) P. A. Lindahl, E. Mu¨nck and S. W. Ragsdale, J. Biol. Chem., 1990,
265, 3873; (b) P. A. Lindahl, S. W. Ragsdale and E. Mu¨nck, J. Biol.
Chem., 1990, 265, 3880; (c) S. W. Ragsdale, H. G. Wood and W. E.
Antholine, Proc. Natl. Acad. Sci. U. S. A., 1985, 82, 6811.
12 E. I. Solomon, T. C. Brunold, M. I. Davis, J. N. Kemsley, S.-K. Lee, N.
Lehnert, F. Neese, A. T. Skulan, Y.-S. Yang and J. Zhou, Chem. Rev.,
2000, 100, 235.
oscillation range of 0.3◦. The frame data were integrated and corrected
for absorption using a Rigaku/MSC CrystalClear program package. The
structure was solved by a direct method (SIR-97), and was refined by full-
matrix least squares on F2 using SHELXL-97 in a Rigaku/MSC Crystal
Structure program package. Anisotropic refinement was applied to all non-
hydrogen atoms except for the disordered atoms, and all hydrogen atoms
were placed at the calculated positions. Crystal data: C60H72N2PS3Ni2;
13 The potential was converted from the Ag/Ag+ to the SCE reference
electrode by adding 0.15 V, see N. G. Connelly and W. E. Geiger,
Chem. Rev., 1996, 96, 877.
orthorhombic; P212121 (#19); a = 13.5400(17), b = 14.7402(19), c =
3
˚
˚
˚
27.322(4) A; V = 5452.9(12) A ; Z = 4; T = 173 K; l = 0.71073 A;
F(000) = 2260; m = 0.874 cm-1; rc = 1.298 g cm-3; 44205 reflections (2q <
55.0◦), 12301 unique (Rint = 0.040); R1 = 0.0477 (I > 2s(I)), wR2 = 0.1672
(all data), GOF = 1.104, Flack parameter = -0.043(13).
14 The yields were calculated on the basis of Co(dmgBF2)2(Me)(Py).
15 They proposed a three step mechanism triggered by single electron
transfer from Ni(I) to the methylcobaloxime. See ref. 7.
This journal is
The Royal Society of Chemistry 2010
Dalton Trans., 2010, 39, 2995–2997 | 2997
©