A square-planar Ni(II) complex with an N2S2 donor set similar to the active centre of nickel-containing superoxide dismutase and its reaction with superoxide

Article abstract of DOI:10.1039/b925755a

The structure around the metal centre of a Ni(ii) complex with an N ₂S₂ square-planar geometry, 1, prepared as a model compound of the NiSOD active site was drastically changed upon addition of potassium superoxide (KO₂). The Royal Society of Chemistry.

Full text of DOI:10.1039/b925755a

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A square-planar Ni(II) complex with an N2S2 donor set similar to the
active centre of nickel-containing superoxide dismutase and its reaction
with superoxidew
Daisuke Nakane,a Shin-ich Kuwasako,a Michiharu Tsuge,a Minoru Kubo,b
Yasuhiro Funahashi,a Tomohiro Ozawa,a Takashi Ogurab and Hideki Masuda*a
Received (in Cambridge, UK) 8th December 2009, Accepted 28th January 2010
First published as an Advance Article on the web 12th February 2010
DOI: 10.1039/b925755a
The structure around the metal centre of a Ni(II) complex with
an N2S2 square-planar geometry, 1, prepared as a model
compound of the NiSOD active site was drastically changed
upon addition of potassium superoxide (KO2).
provided by two amine nitrogens and two thioether sulfurs in
the equatorial plane. The bond lengths of Ni–N (1.931(4) A) and
Ni–S (2.197(1) A) are consistent with those of diamine- or
dithioether-type square-planar Ni(II) complexes with three five-
membered chelate rings.4–7 Complex 1 has an absorption band
characteristic of Ni(II) complexes with a square-planar structure
at 474 nm (e/Mꢀ1 cmꢀ1 210) in MeOH. This band is lower in
energy than those of related N2S2-type Ni(II) complexes reported
previously; [Ni(emi)]2ꢀ (diamide-dithiolate-type, 430 nm (340)),4
Ni-containing superoxide dismutase (NiSOD) catalyzes dis-
proportionation of superoxide anion to dioxygen and hydro-
gen peroxide through the following reactions:1
Ni(II) + O2 + 2H+ - Ni(III) + H2O2
(i)
ꢀ
[Ni(BEAAM)]ꢀ
(monoamide-monoamine-dithiolate-type,
461 nm (290)),5 [Ni(bmmp-dmed)] (diamine-dithiolate-type,
480 nm),6 [Ni(ema)ꢁ(Me)2] (diamide-dithiolether-type, 416 nm
(360))7 and reduced NiSOD (450 nm (480)).8 The Ni(II) complex
1 produces reversible and quasi-reversible redox potentials
corresponding to Ni(I)/(II) and Ni(II)/(III) couples at ꢀ0.68 and
1.71 V (vs. NHE), respectively. The potential for Ni(II)/(III) is
much higher than the analogous potential of other Ni complexes
with diamide-dithiolate- (ꢀ0.50 V), diamide-dithioether-
(1.24 V), diamine-dithiolate- (1.04 V (Epa)), or monoamide-
monoamine-dithiolate-donor sets (ꢀ0.04 V).4–7 The absorption
band observed in the lower energy region and the higher value of
the redox potential indicate that the ligating atoms are weaker
donors than those of typical N2S2-type Ni(II) complexes.
The reaction of the Ni(II) complex 1 with NaBH4 produces
an EPR spectrum typical of a low-spin dx2ꢀy2 ground state
(gJ = 2.25, g> = 2.07) as shown in Fig. 2(A). This implies that
the Ni(II) complex 1 is reduced to the Ni(I) state while retaining
square-planar geometry. After exposure of this solution to
air, the EPR spectrum is converted to a spectrum typical
of a dz2 ground state with triplet hyperfine splitting in
the gJ region (Fig. 2(B)). This EPR spectral change suggests
that the Ni(I) complex is oxidized by O2 to a low-spin
Ni(III) state.
ꢀ
Ni(III) + O2 - Ni(II) + O2
(ii)
The crystal structure of the active site has been reported for
both the Ni(II) and Ni(III) states. In the Ni(II) state, the central
metal ion has a square-planar geometry with ligands provided
by one amine nitrogen of the terminal histidine, one amide
nitrogen of the peptide backbone, and two cysteine thiolates at
equatorial positions.2 When the Ni(II) state is oxidized to the
Ni(III) state, the coordination structure is converted to square-
pyramidal geometry and the imidazolyl group of the terminal
histidine moves to an axial position and ligates to the Ni centre
with a relatively long ligand–metal distance of B2.5 A
(Scheme 1).2 Evidence for this coordination structure is pro-
vided by an EPR spectral feature typical of a dz2 ground state
with triplet hyperfine splitting in the gJ region. On the other
hand, the EPR spectrum of the H1Q mutant of NiSOD (H1Q-
NiSOD) also exhibits triplet hyperfine splitting in spite of the
lack of the terminal histidine imidazole group.3 As a result of
this observation, the structure of the Ni(III) active site of
NiSOD remains controversial.
In this work, we describe a new N2S2-type square-planar
Ni(II) complex (1) as an active site model of NiSOD, and
identify interesting structural behaviour exhibited during the
reaction of 1 with superoxide.
The crystal structure of 1, obtained by vapour diffusion of
Et2O into an acetone solution of 1, is shown in Fig. 1 together
with selected bond lengths and angles.z The Ni(II) centre of 1
has C2 symmetry with square-planar geometry. Ligands are
a Department of Frontier Materials, Graduate School of Engineering,
Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya
466-8555, Japan. E-mail: masuda.hideki@nitech.ac.jp
b Graduate School of Life Science, University of Hyogo, 3-2-1 Kouto,
Kamigori-cho, Ako-gun, Hyougo 678-1297, Japan
w Electronic supplementary information (ESI) available: Experimental
section and additional figures. CCDC 757339. For ESI and crystal-
lographic data in CIF or other electronic format see DOI: 10.1039/
b925755a
Scheme 1 Schematic structures of the NiSOD active site in the
reduced (left) and oxidized (right) states.
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Fig. 1 ORTEP drawing of the cation moiety of 1 with thermal
ellipsoids drawn at 50% probability. The hydrogen atoms and counter-
anions (perchlorate) are omitted for clarity. The atoms with and without
an asterisk are related by the crystallographic twofold axis. Selected
bond distances (A) and angles (1): Ni–N 1.924(3), Ni–S 2.1981(10),
N1–Ni–N1* 87.26(13), N1–Ni–S1* 173.97(8), N1–Ni–S1 88.60(9),
N1*–Ni–S1* 88.60(9), S1–Ni–S1* 95.85(4).
Scheme 2 The reaction scheme of complex 1 treated with NaBH4 and
subsequent addition of O2 (left), and that of 1 with KO2.
oxygen atoms. One of two amine nitrogen atoms may be
changed from the equatorial position to the axial position of
the new equatorial plane. The high structural flexibility of the
amine nitrogen site may permit such a structural change.
Although the EPR spectrum of a dz2 ground-state Ni(III)
complex with triplet hyperfine splitting in the gJ region is
observed only in cases where the axial position of the Ni(III)
centre is occupied by an exogenous nitrogen-containing ligand
with I = 1,4,10–13 the structural changes described above are
permissible. The Ni(III) ion has a rigid square-planar structure
with imine or amide nitrogen ligands. This structure permits
exogenous ligands to bind only at the axial positions.4,10–12
Therefore, higher structural flexibility of the ligands is neces-
sary in order to enable the drastic structural change to occur as
shown in Scheme 2. It is expected that the oxidized product of
1 is more flexible than other Ni(III) complexes, because there is
no rigid moiety. In fact, such ‘‘kicked-up’’ structures were
previously reported for Cu(II) and Ni(II) complexes containing
a thioether sulfur.14–17 In these previous reports, the thioether
sulfurs result in ‘‘kicked-up’’ structures when a stronger ligand
is provided.
Fig. 2 EPR spectra observed (A) after reduction of 1 using NaBH4,
(B) after exposure of the solution to air, and (C) by reaction between 1
and KO2
The same EPR spectrum is also observed as a result of the
reaction between the Ni(II) complex 1 and almost the same
equivalent amount of potassium superoxide (KO2) in MeOH
(Fig. 2(C)). Furthermore, both reaction products have the
same absorption maxima at 300 nm. These spectroscopic
observations indicate that this reaction yields the same pro-
duct as that of the reaction of the Ni(I) complex and O2. This
reaction corresponds to step (i) of the superoxide dismutation
mechanism of NiSOD. The n(O–O) stretching band in the
resonance-Raman spectrum of the reaction product is observed
at 923 cmꢀ1 (Fig. S4, ESIw), a value similar to the n(O–O)
stretching band of side-on Ni-dioxygen species.9
As mentioned previously, the oxidized form of the H1Q
mutant of NiSOD also exhibits triplet hyperfine splitting in the
gJ region in EPR spectra in spite of the lack of the terminal
histidyl imidazole.3 The Ni(II) complex with a flexible N2S2-
type square-planar structure indicates another possibility to
explain this controversial result. From the crystal structure of
native NiSOD, it is estimated that H1Q- and native NiSODs
may also have higher flexibility similar to that of complex 1.2
We therefore propose that the thiolate sulfur atom of Cys6 on
the equatorial plane of active centre of H1Q- and native
NiSOD can be kicked up to the axial position when a stronger
donor such as superoxide anion is present.
The triplet hyperfine splittings (|AJ| = 1.5 mT) are observed
in the gJ region in spite of the fact that no additional
exogenous nitrogen donors are present. These findings suggest
that a nitrogen atom from the supporting ligand coordinates
to the axial position of the Ni(III) centre, thereby altering the
coordination structure of Ni(II) complex 1 from the square-
planar structure to another distinct coordination structure
upon oxidation.
In summary, we have prepared a new square-planar Ni(II)
complex 1 with an N2S2 donor set and characterized it
spectroscopically and electrochemically. The complex is oxi-
dized by KO2 to Ni(III) in MeOH. The same product is also
obtained in a reaction between the reduced product of 1 and
O2. The oxidized state of 1 exhibits an EPR signal with triplet
hyperfine splitting in the gJ region in spite of the lack of an
exogenous nitrogen donor. These findings suggest that the
active site structures of H1Q- and native NiSOD undergo
significant changes upon oxidization.
The EPR spectral behavior indicates that the coordination
geometry is dramatically altered as a result of the reaction. The
reactions between the Ni(I) species and O2 and between the
Ni(II) species and KO2 should both produce side-on Ni(III)-
peroxo species as shown in Scheme 2. One of the two thioether
sulfur atoms moves to the trans position of one of the peroxide
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This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 2142–2144 | 2143

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We gratefully acknowledge the support of this work from a
Grant-in-Aid for Scientific Research from the Ministry of
Education, Science, Sports and Culture and in part by a grant
from the Knowledge Cluster Program.
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z Crystallographic data for 1: C12H28Cl2N2NiO8S2, Mr = 522.09,
monoclinic, C2/c, a = 17.864(4), b = 8.569(2), c = 13.909(3) A, b =
107.176(3)1, V = 2034.2(8) A3, Z = 4, Dc = 1.705 g cmꢀ3, unique
refls. (Rint) 2297 (0.019), R (I 4 2s(I))/Rw (all reflections) = 0.0452/
0.1452, GOF = 1.018.
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2144 | Chem. Commun., 2010, 46, 2142–2144