A bio-inspired switch based on cobalt(II) disulfide/cobalt(III) thiolate interconversion

Article abstract of DOI:10.1002/anie.201402125

Disulfide/thiolate interconversion supported by transition-metal ions is proposed to be implicated in fundamental biological processes, such as the transport of metal ions or the regulation of the production of reactive oxygen species. We report herein a mononuclear dithiolate Co^III complex, [Co^IIILS(Cl)] (1; LS=sulfur containing ligand), that undergoes a clean, fast, quantitative and reversible Co^II disulfide/Co ^III thiolate interconversion mediated by a chloride anion. The removal of Cl^- from the Co^III complex leads to the formation of a bis(μ-thiolato) μ-disulfido dicobalt(II) complex, [Co ₂^II,IILSSL]²⁺ (2²⁺). The structures of both complexes have been resolved by single-crystal X-ray diffraction; their magnetic, spectroscopic, and redox properties investigated together with DFT calculations. This system is a unique example of metal-based switchable M ⁿ₂-RSSR/2 M⁽ⁿ⁺¹⁾-SR (M=metal ion, n=oxidation state) system that does not contain copper, acts under aerobic conditions, and involves systems with different nuclearities. A switchable Co^II ₂ disulfide/Co^III thiolate system (see scheme; filled circles show the color change) is stable under aerobic conditions. It offers the chance to understand the disulfide/thiolate interconversion supported by transition-metal ions, which is proposed to be involved in various fundamental biological processes.

Full text of DOI:10.1002/anie.201402125

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Angewandte
Communications
DOI: 10.1002/anie.201402125
Bioinorganic Chemistry
A Bio-Inspired Switch Based on Cobalt(II) Disulfide/Cobalt(III)
Thiolate Interconversion**
Marcello Gennari,* Bertrand Gerey, Nikita Hall, Jacques Pꢀcaut, Marie-Noꢁlle Collomb,
Mathieu Rouziꢂres, Rodolphe Clꢀrac, Maylis Orio, and Carole Duboc*
Abstract: Disulfide/thiolate interconversion supported by
transition-metal ions is proposed to be implicated in funda-
mental biological processes, such as the transport of metal ions
or the regulation of the production of reactive oxygen species.
We report herein a mononuclear dithiolate CoIII complex,
[CoIIILS(Cl)] (1; LS = sulfur containing ligand), that under-
goes a clean, fast, quantitative and reversible CoII disulfide/
CoIII thiolate interconversion mediated by a chloride anion.
The removal of ClÀ from the CoIII complex leads to the
formation of a bis(m-thiolato) m-disulfido dicobalt(II) com-
plex, [Co2II,IILSSL]2+ (22+). The structures of both complexes
have been resolved by single-crystal X-ray diffraction; their
magnetic, spectroscopic, and redox properties investigated
together with DFT calculations. This system is a unique
role in the folding and stability of most proteins. When this
reaction becomes reversible, it can switch “on” or “off” the
reactivity of a protein.[1] On the other hand, thiolates act as
terminal or bridging ligands for transition-metal ions to
generate self-assembled complexes of different nuclearities.[2]
The idea that metal ions can play an active role in the
disulfide/thiolate interconversion of essential biological pro-
cesses has only emerged during the last decade.[3] However,
this hypothesis has never been undoubtedly demonstrated nor
completely understood.[4]
In chemistry, the disulfide/thiolate interconversion has
been largely explored as well as the effect of a metal ion on
the kinetics. However, only a few investigations, limited to
copper complexes, report on the role of the metal ion directly
bound to the sulfur atoms involved in the RSSR/2RSÀ
interconversion.[5] In those three examples, the interconver-
sion is mediated by either halides or protons and requires
anaerobic conditions. Surprisingly, such processes have never
been reported for other transition-metal ions.
example of metal-based switchable Mn -RSSR/2M(n+1)-SR
2
(M = metal ion, n = oxidation state) system that does not
contain copper, acts under aerobic conditions, and involves
systems with different nuclearities.
T
he conversion of thiolates into disulfide bridges is one of
the major biological redox processes due to its fundamental
We report herein on a mononuclear dithiolate CoIII
complex, [CoIIILS(Cl)] (1, LS = sulfur containing ligand),
that undergoes a very clean, quantitative and fully reversible
CoIII thiolate/CoII disulfide interconversion mediated by
a chloride anion (Scheme 1). Remarkably, compound 1 is
a rare example of a triplet five-coordinated CoIII complex.[6]
The removal of the ClÀ ion from the CoIII complex leads to the
formation of a bis(m-thiolato) m-disulfido dicobalt(II) com-
plex, [Co2II,IILSSL]2+ (22+), containing the unusual {M2S2(SS)}
core, only found in Mn, Re and Ir complexes until now.[7]
The mononuclear complex 1 was obtained as black
crystals by electrochemical oxidation of [CoIILS][8] at
À0.50 V vs Fc/Fc+ (Fc = [(h-C5H5)2Fe]) in presence of
Et4NCl as electrolyte in CH3CN. The X-ray structure of
1 (Figure 1) shows that the CoIII ion is in the center of
a distorted square pyramidal N2S2Cl coordination sphere,
with the two N and two S atoms of the ligand located in the
equatorial plane, and the ClÀ ion occupying the axial position.
The CoIII ion is shifted 0.485 ꢀ from the mean N2S2 plane
[*] Dr. M. Gennari, B. Gerey, Dr. N. Hall, Dr. M.-N. Collomb,
Dr. C. Duboc
Universitꢀ Joseph Fourier Grenoble 1/CNRS
Dꢀpartement de Chimie Molꢀculaire, UMR-5250
Laboratoire de Chimie Inorganique Redox
Institut de Chimie Molꢀculaire de Grenoble FR-CNRS-2607
BP-53, 38041 Grenoble Cedex 9 (France)
E-mail: marcello.gennari@ujf-grenoble.fr
carole.duboc@ujf-grenoble.fr
Dr. J. Pꢀcaut
Laboratoire de Reconnaissance Ionique et Chimie de Coordination
Service de Chimie Inorganique et Biologique
(UMR E-3 CEA/UJF,), CEA-Grenoble, INAC
17 rue des Martyrs 38054 Grenoble cedex 9 (France)
Dr. M. Orio
Univ Lille Nord de France, UDSL
Laboratoire de Spectrochimie Infrarouge et Raman
CNRS UMR 8516, BP 83, Lille (France)
À
toward the axial Cl ligand. As expected, the Co S and the
II
[8]
À
M. Rouziꢁres, Dr. R. Clꢀrac
CNRS, CRPP, UPR 8641, 33600 Pessac (France)
and
Co N bonds in 1 are slightly longer than those in [Co LS].
From the magnetic properties of 1, it can be concluded
that it is an S = 1 CoIII species both in solid state and in
solution. The cT product at 320 K of 1.3 cm3 KmolÀ1
(Figure 2) is in agreement with the expected values for such
S = 1 species. Its decrease observed at low temperature is
consistent with very large zero-field splitting, estimated by
fitting the experimental data with D/kB =+ 50(1) K and g =
2.27(5) (with H = DST,z2). For comparison, the unique pre-
viously reported D value for an S = 1 five-coordinated CoIII
Univ. Bordeaux, CRPP, UPR 8641, 33600 Pessac (France)
[**] M.G. thanks the CNRS for a post-doctoral fellowship. N.H. thanks
the Dꢀpartement de Chimie Molꢀculaire (DCM) for her Ph.D
fellowship. M.R. and R.C. thank the University of Bordeaux, the
Rꢀgion Aquitaine, the ANR and the CNRS. This work has been
partially supported by the Labex ARCANE (ANR-11-LABX-0003-01).
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201402125.
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center, is retained in solution. The
absorption spectrum of the brown
1 solution in CH2Cl2 (Figure 3) dis-
plays an intense transition at 477 nm
and two weaker features at 675 nm
and 795 nm, which have been
assigned, based on TD-DFT calcu-
lations, to ligand-to-metal charge
transfer (LMCT) transitions involv-
ing both the chloride anion and
thiolate ligands (Figure S8 in the
Supporting information). The cyclic
voltammogram (CV) of a CH2Cl2
Scheme 1.
Figure 2. Temperature dependence of the cT product (where c is the
molar magnetic susceptibility equal to M/H per cobalt complex)
measured at 0.1 T for 1 and 22+. The solid lines are the best fits of the
experimental data to the models described in the text.
solution of 1 displays a poorly reversible reduction wave at
Epc = À0.78 V vs. Fc/Fc+ (Epa1 = À0.63 V, Epa2 = À0.27 V).
This can be assigned to the CoIII/CoII redox couple followed
by a partial decoordination of the ClÀ ion. An irreversible
oxidation wave is observed at Epa =+ 0.50 V (Epc = À0.08 V)
(Figure 4), most likely due to a ligand-based process.
Black crystals of 2(PF6)2·2CH3CN were obtained by
reaction of complex 1 with AgPF6 in CH2Cl2:CH3CN 9:1
(Scheme 1). The dinuclear 22+ complex can be also electro-
generated by an exhaustive electrolysis of [CoIILS] carried out
in CH2Cl2 at 0 V. The X-ray structure of 22+ (Figure 1)
displays a rare {M2S2(SS)} core, with a disulfide binding the
two CoII ions in a cis-m-1,2 mode. The slightly shorter Co N
À
distances in 22+ in comparison with those in the CoIII complex
1, are consistent with the + II oxidation state for both Co ions.
A C2 axis is at the origin of the structural equivalence of the
two CoII centers. Each CoII ion displays a highly distorted
square-pyramidal geometry, with two N atoms and two m-S
atoms of the ligand forming the square planar base and one S
Figure 1. ORTEP-type views (thermal ellipsoids set at 30% probability,
hydrogen atoms removed for clarity) of a) 1, b) 22+, c) the binuclear
{N4Co2S2(SS)} core of 22+
.
atom of the disulfide bridge in axial position. As expected, the
II
À
axial Co SS-S bond (2.5341(8) ꢀ) is significantly longer than
II
complex is of + 154 K.[6] The effective magnetic moment
determined in CH2Cl2 solution (meff = 2.44 mB at 208C by
Evans method, corresponding to cT= 0.74 cm3 KmolÀ1)[9]
evidence that the triplet state is conserved in solution
(2.82 mB is expected for S = 1), thus confirming that the
mononuclear structure of 1, with a five-coordinate CoIII
the basal Co (m-Sthiolate) bonds (2.3796(8) and 2.3272(7) ꢀ),
À
the latter being in the expected range (2.21–2.39 ꢀ).[10] The
long distance between the two Co ions (3.1188(5) ꢀ) implies
the absence of a direct metal–metal bond. The temperature
dependence of the magnetic susceptibility of 2-
(PF6)2·2CH3CN was collected over the 300–1.8 K temper-
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(PF6)]+). The UV/Vis spectrum of the pale yellow solution of
22+ (Figure 3) displays several low-intense shoulders at
around 400, 505, and 600 nm. The CV of 22+ (Figure 4)
shows an irreversible two-electron reduction process[11]
located at Epc = À0.74 V (Epa = À0.10 V), attributed to the
reduction of the disulfide bridge. Two consecutive one-
electron oxidation processes, electrochemically reversible,
are located at E1/2 =+ 0.56 V and + 0.68 V (DEp = 140 mV
and 80 mV, respectively). These can be assigned to the
oxidation of either the CoII ions or the remaining thiolates.
Remarkably, the cathodic peak of 22+ is only 40 mV shifted
(to less negative potentials) with respect to the cathodic peak
of 1, assigned to the reduction of CoIII into CoII.
In presence of two equivalents of Et4NCl, the dinuclear
22+ complex is immediately and quantitatively converted into
two equivalents of the mononuclear 1 species in CH2Cl2 under
aerobic conditions (208C), as shown by UV/Vis spectroscopy
(Figure 3). This internal redox process, induced by the
coordination of one chloride anion on each Co center,
involves the reduction of the disulfide bridge with the
concomitant oxidation of the CoII centers of 22+. This reaction
is completely reversible as the stoichiometric addition of
Li[B(C6F5)4] is sufficient to quantitatively regenerate 22+ from
1 (Figure 3). The process is clean without formation of any by-
products. Indeed, 22+ is the only species detected in solution
after the addition of Li[B(C6F5)4] to 1, as attested by ESI mass
spectrometry (signal at m/z 1953.1 for [2(B(C6F5)4)]+) and
electrochemistry (the CV being identical to that of 22+). The
reverse is also true, that is, when adding two equivalents of
Et4NCl to 22+, the resulting CV is identical to that of 1. More
interestingly, this chemical interconversion can be repeated
several times (at least 10 cycles) without loss of efficiency
(Figure 3).
Figure 3. a) UV/Vis spectra of 1 (0.19 mm in CH2Cl2, 1 cm path length,
room temperature, aerobic conditions) recorded before (c)
and (a) after the addition of Li[B(C6F5)4] (1.05 equiv) forming 22+
.
b) By monitoring the absorbance at 477 nm, the complete reversibility
of the process is attested by a subsequent addition of Et4NCl
(1.05 equiv): no loss of conversion is observed after 10 cycles. c) UV
cells with 1 (right) and 22+ (left).
The geometric and electronic changes induced on 1 by
removing the cobalt-bound ClÀ ion have been tentatively
rationalized through DFT calculations. The Mulliken spin
population analysis performed on the DFT-optimized struc-
ture of [CoLS]+ highlights a remarkable increase of the spin
distribution on the sulfur atoms in comparison to 1 (0.18 for
[CoLS]+ and 0.01 for 1, Figure S9). The clear “thiyl” character
of the thiolates can then explain their enhanced reactivity and
the immediate formation a disulfide bridge between two
[CoLS]+ units to generate 22+. Such a phenomenon has been
described for a mononuclear NiII thiyl radical complex, which
Figure 4. Cyclic voltammograms of an 1.70 mm solution of 1 (a)
and an 0.85 mm solution of 22+ (c) in CH2Cl2, 0.1m Bu4NPF6
(carbon vitreous electrode, scan rate of 100 mVsÀ1, potentials vs Fc+/
Fc).
rapidly undergoes an irreversible dimerization process involv-
[12]
À
ing the formation of an S S bond.
Two conditions seem to be required for such metal-based
disulfide/thiolate interconversion process to occur reversibly.
First, the redox potential of the RSSR/2RSÀ and Mn+/M(nÀ1)+
redox couples should be close enough to allow a small
structural modification to address the direction of the internal
electron transfer between the ligand and the metal. In this
specific case, this is owing to the coordination of a ClÀ ion that
the redox potential of the CoIII/CoII redox couple becomes
lower than that of the RSSR/2RSÀ couple, thus stabilizing the
CoIIISR species. In contrast, decoordination of the ClÀ ion
ature range (Figure 2). The magnetic behavior is consistent
with the presence of two high spin CoII ions (S = 3/2)
interacting by a strong antiferromagnetic coupling, J/kB =
À200(5) K (g = 2.37(5); H = À2JS1 S2). The effective mag-
netic moment determined in CH2Cl2 solution (meff = 3.77 mB at
208C, corresponding to cT= 1.8 cm3 KmolÀ1) is consistent
with the magnetic properties measured on the powder. The
dinuclear structure of 22+ is thus retained in solution, as
confirmed by ESI mass spectrometry (m/z 1419.2 for [2-
leads to the stabilization of the CoII (R)SSR form with respect
2
to the CoIIISR one. Secondly, the chemical reversibility of the
process seems to be also favored by the disulfido bridge
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highly reactive thiyls and/or free thiolate species during the
interconversion process.
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In conclusion, we have described a rare example of
a metal-based switchable system involving a disulfide/thiolate
interconversion. Most importantly, this work reports the first
Mn -(R)SSR/2M(n+1)-SR switch (n = oxidation state) that
2
1) does not contain copper, 2) acts under aerobic conditions,
and 3) involves systems with different nuclearities. In addi-
tion, these results also confirm that an external stimulus (in
this case, the addition of a chloride anion) can lead to the fine-
tuning of the electronic properties of the metal ion, thereby
permitting the shift of the disulfide/thiolate equilibrium.
However, the exact role of the mediator deserves to be
further elucidated with the determination of the key proper-
ties for the process to occur. More interestingly, this work
opens the door to a broader field of applications if other
external stimuli such as pH value, light, or pressure can
control this molecular switch.
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Received: February 5, 2014
Published online: April 9, 2014
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[11] The two-electron reduction peak is slightly resolved in two one-
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Keywords: bioinorganic chemistry · cobalt complexes ·
disulfide/thiolate interconversion · sulfur ligands
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