Experimental and computational investigation of thiolate alkylation in NiII and ZnII complexes: Role of the metal on the sulfur nucleophilicity

Article abstract of DOI:10.1021/ic200899w

The biologically relevant S-alkylation reactions of thiolate ligands bound to a transition metal ion were investigated with particular attention paid to the role of the metal identity: Zn^II versus Ni^II. The reactivity of two mononucl

Full text of DOI:10.1021/ic200899w

ARTICLE
pubs.acs.org/IC
Experimental and Computational Investigation of Thiolate Alkylation
in NiII and ZnII Complexes: Role of the Metal on the Sulfur
Nucleophilicity
Marcello Gennari,† Marius Retegan,† Serena DeBeer,‡ Jacques Pꢀecaut,§ Frank Neese,||,^
Marie-No€elle Collomb,† and Carole Duboc*,†
†Universitꢀe Joseph Fourier Grenoble 1/CNRS, Dꢀepartement de Chimie Molꢀeculaire, UMR-5250, Laboratoire de Chimie Inorganique
Redox, Institut de Chimie Molꢀeculaire de Grenoble FR, CNRS-2607, BP-53, 38041 Grenoble Cedex 9, France
‡Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States
§Laboratoire de Reconnaissance Ionique et Chimie de Coordination, Service de Chimie Inorganique et Biologique, UMR E-3 CEA/UJF,
CNRS, CEA-Grenoble, INAC, 17 Rue des Martyrs 38054 Grenoble Cedex 9, France
Institute for Physical and Theoretical Chemistry, Universit€at Bonn, Wegelerstrasse 12, D-53113 Bonn, Germany
^Max-Planck-Institut f€ur Bioanorganische Chemie, Stiftstrasse 34-36, D-45470 M€ulheim an der Ruhr, Germany
S Supporting Information
b
ABSTRACT: The biologically relevant S-alkylation reactions of
thiolate ligands bound to a transition metal ion were investi-
gated with particular attention paid to the role of the metal
identity: ZnII versus NiII. The reactivity of two mononuclear
diamine dithiolate Zn and Ni complexes with CH3I was studied.
With the [ZnL] complex (1) (LH2 = 2,20-(2,20-bipyridine-6,60-
diyl)bis(1,1-diphenylethanethiolate)), a double S-methylation
occurs leading to [ZnLMe2I2] (1Me2), while with [NiL] (2), only
the mono-S-methylated product [NiLMe]I(2Me) is formed. Com-
plexes 1 and 1Me2 have been characterized by X-ray crystal-
lography, while the structures of 2 and 2Me have been previously described. The kinetics of the first S-methylation reaction,
investigated by 1H NMR, is found to follow a second-order rate law, and the activation parameters, ΔHq and ΔSq, are similar for both
1 and 2. S K-edge X-ray absorption spectroscopy measurements have been carried out on 1, 2, and 2Me, and a TD-DFT approach
was employed to interpret the data. The electronic structures of 1 and 2 calculated by DFT reveal that the thiolateꢀmetal bond is
predominantly ionic in 1 and covalent in 2. However, evaluation of the molecular electrostatic potential minima around the lone
pairs of the thiolate sulfur atoms gives similar values for 1 and 2, suggesting a comparable nucleophilicity. The DFT-optimized
structures of the mono-S-methylation products have been calculated for the Zn and Ni complexes. Molecular electrostatic potential
analysis of these products shows that (i) the nucleophilicity of the remaining thiolate sulfur atom is partly quenched for the Ni
complex while it is conserved in the Zn complex and, more importantly, (ii) that the accessibility for the methyl transfer agent to the
remaining thiolate is favored for the mono-S-methylated Zn complex compared to the Ni one. This explains the absence of a double
S-methylation process in the case of the Ni complex at room temperature.
’ INTRODUCTION
mononuclear thiolate ZnII complexes has been investigated in
numerous studies.9ꢀ21 Generally, S-alkylation reactions can
follow two different pathways: (i) a dissociative mechanism, in
which the metalꢀsulfur bond is split, followed by a SN2 reaction
involving the free thiolate and (ii) an associative mechanism, in
which the reaction occurs via a SN2 reaction involving the bound
thiolate. It has been demonstrated that for anionic tetrathiolate
Zn complexes a dissociative mechanism is operative,10,22 while
for neutral thiolate Zn complexes and for the Ada protein an
associative mechanism is most likely.11ꢀ13,23ꢀ26
Transition metal ions with thiolate ligands are found in the
active sites of numerous metalloproteins and involved in a wide
variety of biological processes.1ꢀ4Within this large family of
metalloproteins, some active sites exploit the nucleophilicity of
the thiolate sulfur atom to perform S-oxygenation and S-alkyla-
tion reactions.5 Indeed, post-translational modifications in nitrile
hydratase implicate S-oxygenation reactions via mononuclear
thiolate CoIII or FeIII active sites.2 In addition, ZnII-dependent
thiolate methylation proteins have been identified including
methionine synthase,6 farnesyl transferase,7 and, most prominently,
the Ada protein implicated in DNA repair.8
In an effort to obtain insight into the S-alkylation mechanism
of these Zn(II) metalloenzymes, the reactivity of synthetic
Received: April 28, 2011
Published: September 20, 2011
r
2011 American Chemical Society
10047
dx.doi.org/10.1021/ic200899w Inorg. Chem. 2011, 50, 10047–10055
|

Inorganic Chemistry
ARTICLE
Scheme 1
Even if none of the Ni thiolate-containing enzymes achieve
S-oxygenation or S-alkylation reaction, synthetic mononuclear
thiolate Ni complexes have also been extensively investigated
because of their efficient reactions with dioxygen5,27ꢀ31 or alkyl15,32ꢀ37
transfer agent. It appears from these studies that series of mono-
nuclear NiII and ZnII thiolate complexes synthesized with the
same ligand exhibit different reactivity toward S-alkylation.
Indeed, the nature of the byproduct varies as a function of the
metal: the resulting thioether remains generally bound to the Ni
center, while it dissociates from the Zn center. For dithiolate
complexes, only one sulfur atom is rapidly alkylated in the Ni
complexes, while the mono-S-alkylated product is never isolated
in the corresponding Zn complexes because of the very fast
second S-alkylation reaction.
Figure 1. ORTEP drawing of (a) [ZnL] (1) and (b) [ZnLMe2I2] (1Me2);
30% thermal ellipsoids. Hydrogen atoms are omitted for clarity.
Table 1. Selected Bond Lengths (Å) and Angles (deg) for
[ZnL] (1) and [ZnLMe2I2] (1Me2
)
1
2
Zn(1)ꢀN(1)
Zn(1)ꢀN(2)
Zn(1)ꢀS(1)
Zn(1)ꢀS(2)
2.116(5) Zn(1)ꢀN(1)
2.117(5) Zn(1)ꢀN(2)
2.271(2) Zn(1)ꢀI(1)
2.284(2) Zn(1)ꢀI(2)
S(1)ꢀC(25)
2.045(4)
2.061(4)
2.5432(7)
2.5384(7)
1.769(5)
1.774(6)
Thus, there is a need to define the factors that govern the
nucleophilic reactivity of mononuclear ZnII and NiII thiolate
complexes with the aim of eventually being able to predict it. In
this context, this work is focused on the reactivity toward CH3I of
two mononuclear dithiolate N2S2 Zn and Ni complexes, which
has been rationalized by a deep investigation of their electronic
structure. We report here the synthesis and characterization of
the new mononuclear bisamine dithiolate N2S2 [ZnL] complex (1)
(H2L = 2,20-(2,20-bipyridine-6,60-diyl)bis(1,1-diphenylethanethiol)
(Scheme 1). We have shown that 1 reacts with CH3I, generating the
double S-methylated complex, [ZnLMe2I2] (1Me2) (Scheme 1). We
also compared the reactivity of 1 with that of the previously
described isostructural NiII complex, [NiL] (2),38 which leads to
S(2)ꢀC(45)
N(1)ꢀZn(1)ꢀN(2)
N(1)ꢀZn(1)ꢀS(1)
N(1)ꢀZn(1)ꢀS(2)
N(2)ꢀZn(1)ꢀS(1)
N(2)ꢀZn(1)ꢀS(2)
S(1)ꢀZn(1)ꢀS(2)
77.9(2)
97.8(1)
N(1)ꢀZn(1)ꢀN(2)
N(1)ꢀZn(1)ꢀI(1)
N(1)ꢀZn(1)ꢀI(2)
N(2)ꢀZn(1)ꢀI(1)
N(2)ꢀZn(1)ꢀI(2)
I(1)ꢀZn(1)ꢀI(2)
81.34(19)
114.86(10)
109.19(11)
109.47(11)
113.75(10)
121.37(3)
143.4(1)
146.4(1)
97.0(1)
104.98(7)
the mono-S-methylated complex, [NiLMe]I (2Me 39
) (Scheme 1).
described NiII complex (2).38 In contrast, in the presence of
CuCl, the L2ꢀ ligand reacts with CH2Cl2 to form a dinucleating
ligand, leading to a dicopper complex.40
The S-methylation mechanism was investigated by kinetic ex-
periments performed on 1 and 2. S K-edge X-ray absorption
spectroscopy (XAS) combined with quantum chemistry have
been used to explore the electronic structures of the complexes 1,
2, and 2Me and especially the nature of the metalꢀthiolate bond,
related to the reactivity of the initial and mono-S-methylated
complexes.
The coordination sphere of the ZnII ion consists of two
nitrogen atoms of the bipyridine unit and two sulfur atoms of
the aliphatic thiolates of L2ꢀ. The geometry around the central
Zn ion is in between a square plane and a tetrahedron, with a twist
angle of 46.38ꢀ (angle between the NZnN and SZnS planes). In
contrast, the corresponding NiII complex, 2, displays a pseudo-
square-planar geometry with a twist angle of 29.15ꢀ. The other
previously described dithiolate N2S2 ZnII complexes present
geometries closer to a tetrahedron regardless of whether the
ligands lead to 5- or 6-membered N,S chelates.41ꢀ44 As expected,
the ZnꢀS (2.271(2) and 2.284(2) Å) and ZnꢀN (2.116(5) and
2.117(5) Å) bond distances in 1 are slightly longer than those of
’ RESULTS AND DISCUSSION
1. X-ray Structure of [ZnL] (1) and [ZnLMe2I2] (1Me2). The
structures of complexes 1 and 1Me2 were determined by X-ray
crystallography (Figure 1). Selected bond distances and angles
are provided in Table 1. Complex 1 is crystallized in CH2Cl2 as a
mononuclear dithiolate N2S2 ZnII complex, as for the previously
10048
dx.doi.org/10.1021/ic200899w |Inorg. Chem. 2011, 50, 10047–10055

Inorganic Chemistry
ARTICLE
2 (NiꢀS 2.173(1) and 2.176(1) Å; NiꢀN 1.934(2) and
1.935(2) Å).
Table 2. Second-Order Rate Constants (k2) for Reactions of
1 (1.1 mM) and 2 (1.4 mM) with CH3I (mono-S-methylation)
in CDCl3 at Different Temperatures
In the dimethyl complex 1Me2, the zinc anion is coordinated
to two nitrogen atoms of the bipyridine units of LMe2 and two
iodide ions in a pseudo-tetrahedral geometry with a twist angle
of 85.95ꢀ. Coordination of the iodide ions to the Zn ion is
confirmed by the typical ZnꢀI bond lengths observed in 1Me2
(2.5384(7) and 2.5384(7) Å).11,45 On the other hand, the long
ZnꢀS(CH3) distances (5.87 and 5.89 Å) unambiguously estab-
lish that the thioethers are not bound to the metal, in contrast
to 2Me. The ZnꢀN distances (2.045(4) and 2.061(4) Å) are
significantly shorter than those of 1. The IꢀZnꢀI angle
(121.37(3)ꢀ) is affected by the small NꢀZnꢀN angle
(81.34(19)ꢀ) that is dictated by the rigidity of the bipyridine unit.
2. Electrochemical Properties of [ZnL] (1). The electroche-
mical properties of 1 were investigated in DMF. The cyclic
voltammogram displays a quasi reversible wave at E1/2 = ꢀ1.95 V
vs Fc/Fc+ (ΔEp = 70 mV) corresponding to a one-electron
reduction process (Figure S1, Supporting Information). On
the positive potential side, an irreversible wave is observed at
k2 (Mꢀ1 sꢀ1
)
3
T (K)
1
2
285.4
294.0
302.5
311.1
8.8(5) ꢁ 10ꢀ4
1.5(2) ꢁ 10ꢀ3
3.1(1) ꢁ 10ꢀ3
6.1(6) ꢁ 10ꢀ3
6.0(2) ꢁ 10ꢀ3
1.25(5) ꢁ 10ꢀ2
2.2(1) ꢁ 10ꢀ2
3.3(2) ꢁ 10ꢀ2
Ep = +0.43 V. These two redox processes are obviously
a
ligand based, consistent with the filled d-orbital manifold of
the ZnII ion. The anodic wave is thus assigned to an oxidation oc-
curring at the thiolate sites, while the cathodic wave is attributed to
reduction of the bipyridine unit.
3. Methylation Studies. Reaction of 1 and 2 in the presence of
an excess of CH3I was studied in CH2Cl2, and the metal-
containing products were analyzed by mass spectrometry. The
S-methylation reaction is selective since in the case of the Zn
complex only the doubly S-methylated complex [ZnLMe2I2]
(1Me2) is formed, while in the case of the Ni complex, the
mono-S-methylated complex [NiLMe]I (2Me) is exclusively
produced after 12 h (Figure S2, Supporting Information). Both
products were characterized by X-ray crystallography (see above
for 1Me2 and ref 39 for 2Me). The inability of the thioethers to
coordinate to the Zn center in 1Me2 is consistent with previous
studies demonstrating that upon S-alkylation the resulting thioether
generally dissociates from the metal center.9,12,23,43 Indeed, only a
few examples of Zn products with bound thioether(s) have been
characterized so far.12,15 Conversely, upon S-alkylation, the gener-
ated thioether commonly remains bound to the Ni center.34ꢀ37
Figure 2. Eyring plots for reactions of 1(2) and2(9) withCH3IinCDCl3
determined by means of NMR data. Activation parameters derived from these
plots are ΔHq =+54(3) kJ molꢀ1 and ΔSq =ꢀ115(11) J molꢀ1
3
K
ꢀ1 for 1
3 ꢀ1
3
and ΔHq = +47(4) kJ mol and ΔSq = ꢀ123(12) J molꢀ1
3
K
ꢀ1 for 2.
3
3
ΔHq = 47(4) kJ molꢀ1 and ΔSq = ꢀ123(12) J molꢀ1 Kꢀ1
.
3
3
3
These values are comparable to those obtained on two isostruc-
tural monothiolate N4S Ni and Zn complexes.14 However, in the
former study the NiII ion was high spin. Here, we confirm that the
kinetics of the first S-methylation is comparable for ZnII and low-
spin NiII ions.
The reaction exhibitsanapparent second-order process for both
Zn and Ni complexes, thus strongly suggesting that the same SN2
mechanism is involved. Two mechanisms can be considered
depending on the nature of the active nucleophilic species: the
thiolate either is or is not coordinated to the metal center. On the
basis of earlier studies, it is commonly assumed that for neutral
complexes the mechanism is associative and does not involve a
breaking of the thiolateꢀmetal bond before the S-alkylation
process.13,14,24 The large negative activation entropies together
with the small activation enthalpies values determined for 1 and 2
are also consistent with an associative mechanism.
1
The S-alkylation reaction was monitored by H NMR in
CDCl3 by the smooth decay of 1H NMR resonances typical of
the initial dithiolate metal complexes, with the concomitant
appearance of features that are characteristic of the thioether
metal products of the methylation. For determining the rates of
1
the first S-methylation process, the decay of the H NMR
resonances of the initial species was monitored as a function of
time (Figures S3 and S4, Supporting Information). Kinetic data
were accumulated under pseudo-first-order conditions (large
excess of CH3I), and they can be fitted by assuming second-
order behavior (v = k2[MIIL][CH3I]) for both systems (Scheme 1).
The pseudo-first-order rate constants (kobs) were determined as
a function of the CH3I concentration (kobs = k2[CH3I]).
The k2 values (1.3 ꢁ 10ꢀ3 and 1.1 ꢁ 10ꢀ2 Mꢀ1 sꢀ1 for 1 and
2, respectively, at 21 ꢀC) reveal that with Ni the rate of the
first S-methylation is faster than with Zn (Table 2). The kinetic
parameters of these reactions were determined by analyzing
the temperature dependence of k2 for both 1 and 2. From
the resulting Eyring plots displayed in Figure 2, the activa-
tion parameters ΔHq and ΔSq were extracted: for 1, ΔHq =
All of our attempts to isolate the product of the mono-
S-methylation of 1 have failed, revealing that the second S-alkylation
is faster than the first one. In contrast, for the Ni complex, only
the mono-S-methylated compound was isolated even in the
presence of an excess of CH3I after 12 h of reaction. Formation
of traces of the bis-methylated [NiLMe2 2+
complex is only
]
observed after 1 week of reaction at room temperature by mass
spectrometry. This is consistent with the previous studies of
Darensbourg, which showed that the second S-methylation of
dithiolate Ni complexes is slower than the first one.34
Furthermore, in an attempt to understand the influence of the
iodide on the reaction, we carried out S-methylation reactions
54(3) kJ molꢀ1 and ΔSq = ꢀ115(11) J molꢀ1
3
K
ꢀ1, and for 2,
3
3
10049
dx.doi.org/10.1021/ic200899w |Inorg. Chem. 2011, 50, 10047–10055

Inorganic Chemistry
ARTICLE
using a S-alkylating agent, which does not generate a coordinat-
ing counteranion, Me3OBF4. Mass spectrometry has shown
that for the Ni complex only mono-S-methylation occurs like
with CH3I but the reaction is slower. For the Zn complex, we can
only detect the L ligand even after 6 h of reaction using
Me3OBF4. In contrast, with CH3I, only the di-S-methylated
ligand (LMe2) is observed in the same conditions of reaction.
These results indicate that the presence of the iodide is required
to efficiently perform S-methylation reactions, especially for 1.
In order to explain this difference in reactivity between the
dithiolate Zn and Ni complexes for the S-methylation, we ex-
plored the electronic structure of the complexes by means of S
K-edge XAS experiments and theoretical calculations.
4. Spectroscopic and Theoretical Investigation of the
Methylation Process. 4.1. S K-Edge XAS Experiments. The solid
state S K-edge XAS of complexes 1, 2, and 2Me are shown in
Figure 3. The principal results are reported in Table 3. The
spectrum of 2 displays a pre-edge transition at 2470.5 eV,
assigned to a transition from the S1s orbital to the formally filled
S3p orbital, which gains hole character via mixing with a Ni 3d
orbital (i.e., the transition corresponds to the lowest unoccupied
molecular orbital with sulfur and metal character (LUMO)). The
rising edge transition is located at 2472.4 eV. From the normal-
ized intensity of the pre-edge, a semiquantitative measure of the
NiꢀS bond covalency can be estimated.46ꢀ48 Plastocyanin was
used as a reference, where it has been shown that 1.02 units of
pre-edge intensity corresponds to 38% sulfur character in the
singly occupied molecular orbital of the mononuclear CuII thiolate
complex.49 The pre-edge intensity of 1.16 normalized units thus
corresponds to a contribution of 22% sulfur character in the
LUMO of 2 (∼11% for each thiolate of L). For the previously
described dithiolate [Ni(bme-daco)] (H2-bme-daco = N,N0-bis-
(2-mercaptoethyl)-1,5-diazacyclootane) complex, a larger contri-
bution (23% for each thiolate) has been found.50
The S K-edge XAS of 2Me displays three transitions at 2470.2,
2473.0, and 2474.1 eV. The pre-edge feature at 2470.2 eV is at
similar energy and approximately 60% as intense as the pre-edge
of 2 (0.65 arbitrary units). This mainly reflects the difference
in the number of thiolate sulfur donors in both complexes
(one and two in 2Me and 2, respectively). From its intensity,
the sulfur character of the LUMO can be experimentally esti-
mated as ∼12%, a value comparable to that found for each
thiolate in 2.
The S K-edge XAS spectrum of the ZnII complex (1) exhibits
only two features at 2472.0 and 2473.6 eV. The absence of pre-
edge feature in 1 is consistent with a d10 transition metal ion
complex.
4.2. Theoretical Investigations. 4.2.1. S K-Edge XAS Analysis.
The geometries of complexes 1, 2, and 2Me (denoted 1*, 2*, and
2
Me*) optimized with DFT (see computational details) were used
as the basis for TD-DFT studies of the system’s S K-edge spectra.
The resulting optimized geometries compare well with the crystal-
lographic data, thus validating the computational approach
(Table 4).
By employing the TD-DFT approach, it has been shown that
the pre-edge transition can be properly predicted in the case of
thiolateꢀmetal complexes.51,52 Our calculations adequately re-
produce the key features of the S K-edge XAS spectra of
complexes 2 and 2Me (Figures S5 and S6, Supporting In-
formation). For the two complexes, the energy of the pre-edge
involving the thiolate ligand(s) located at around 2470 eV is well
predicted (calculated 2470.6 and 2470.3 eV for 2* and 2Me*,
respectively) (Table 3). For 2Me*, the pre-edge transition invol-
ving the S-methylated thiolate ligand is calculated at 2472.4 eV,
which is unfortunately overlapping with the rising edge of the
thiolate ligand. This precludes determination of the normalized
intensity of the pre-edge for the S-thioether in the experimental
spectrum. Since the acceptor orbital is the same for both involved
transitions, the relative energy of the S1s orbital for a thiolate
versus a thioether ligand can be measured from the difference
of their pre-edge energies. The value of 2.1 eV is consistent with
a previous study reporting thꢀat the S1s orbital energy difference
between a RSꢀ and a RSO2 ligand was 5.4 eV.50 In fact, the
Figure 3. S K-edge XAS spectra of complexes 1, 2, and 2Me
.
Table 3. S K-Edge XAS Results
exp.
pre-edge
energy
(eV)
calcd
pre-edge
energy
(eV)
exp.
rising edge
energy
calcd rising
edge energy
(eV)
(eV)
2
2Me
RSꢀ
RSꢀ
2470.5
2470.2
2470.6
2470.3
2472.4
2472.4
2474.1
2472.1
2472.2
2473.6
RSCH3
Table 4. Selected Bond Distances (Å) for the DFT Geometry-Optimized Models 1*, 1Me(C)*, 1Me(O)*, 2*, and 2Me* and
Comparison (in parentheses) with the Experimental Data When Available
MꢀS1
MꢀS2
MꢀN1
MꢀN2
MꢀI
1*
1Me(C)
2.281 (2.271)
2.312
2.284 (2.284)
2.817
2.125 (2.116)
2.143
2.125 (2.117)
2.201
*
2.610
1Me(O)
2*
2Me
*
2.267
2.069
2.158
2.573
2.154 (2.173)
2.217 (2.169ꢀ2.174)
2.153 (2.176)
1.904 (1.934)
1.946 (1.899ꢀ1.914)
1.904 (1.935)
1.897 (1.918ꢀ1.959)
*
2.201 (2.172ꢀ2.187)
3.427 (3.778)
10050
dx.doi.org/10.1021/ic200899w |Inorg. Chem. 2011, 50, 10047–10055

Inorganic Chemistry
ARTICLE
Table 5. Lo€wdin Population Analysis for the HOMO and
Natural Population Analysis (NPA) Charges in Complexes 1*,
1
Me(C)*, 1Me(O)*, 2*, and 2Me
*
molecular orbital composition (%)
NPA charges
M
S(1)a S(2)b
M
S(1)a
S(2)b
1*
1Me(C)
1Me(O)
2*
2Me
8
36
68
70
24
18
36
<1
<1
24
1
1.38 ꢀ0.48 ꢀ0.48
Figure 4. Contour plots of the LUMOs in 2* and 2Me*.
*
7
1.34 ꢀ0.52
1.34 ꢀ0.50
0.21
0.19
*
7
S1s orbital of an S-oxidized thiolate is much more stable than the
corresponding orbital in an S-methylated thiolate.
40
43
0.65 ꢀ0.14 ꢀ0.14
*
0.69 ꢀ0.20
0.41
The rising edge is more difficult to predict; however, our TD-
DFT-calculated spectra are consistent with the experimental data
(Figures S5 and S6, Supporting Information). Indeed, the pre-
dicted rising edge for 2 is properly reproduced (the experimental
and calculated values are 2472.4 and 2472.1 eV, respectively).
For 2Me*, the calculated energy of the rising edge implicating the
thioether at 2473.6 eV is consistent with the experimental peak
observed at 2474.1 eV (Figure 3).
a S(1): thiolate sulfur atom. b S(2): thiolate or thioether sulfur atom.
The LUMO53 has a total metal character of only 32% and 40%
for 2* and 2Me*, respectively, and also features strong σ-antibond-
ing interactions with S3p orbitals in both complexes (Figure 4).
The S3p character of the thiolate in the LUMO in 2* is about 10%
for each thiolate and 14% for the remaining thiolate in 2Me*,
consistent with the S K-edge XAS experimental data (11% and
12% for 2 and 2Me, respectively). In 2Me*, the S3p character of the
thioether is smaller, about 6%. Note that these numbers do, of
course, not represent physical observables. However, we found a
very good agreement between theory and experiment.
Figure 5. Contour plots of the HOMOs in 1*, 1Me(C)*, 1Me(O)*, 2*, and
2Me*.
The covalency of the NiꢀSthiolate bond is greater than that of
the NiꢀSthioether bond given the S3p character in the LUMO
(14% and 6% for the thiolate and thioether in 2Me*, respectively).
Furthermore, the combination of experimental and theoretical
data demonstrates that the NiꢀS covalency of the remaining
thiolate in 2Me is not affected by the presence of the neighboring
thioether because of the comparable calculated value for the S3p
character of the thiolate in the LUMO (10% and 14% for 2* and
we obtain similar values for the minima (ꢀ0.078 and ꢀ0.069 au
for 1* and 2*, respectively), suggesting that sulfur atoms in both
complexes are characterized by a comparable nucleophilicity.
This is in agreement with the available experimental data.
4.2.3. Electronic Structures of the Mono-S-Methylated Zn
and Ni Complexes. Looking at the products observed in the
presence of an excess of CH3I, a second S-methylation reaction
occurs exclusively with the Zn complex. To understand this
result, the nucleophilicity of the remaining thiolate sulfur atom in
the mono-S-methylated ZnII and NiII complexes ([MLMe]I with
M = NiII or ZnII) was investigated.
2
Me*, respectively). Equivalent strongly covalent NiꢀSthiolate
bonds therefore characterize both complexes.
4.2.2. Electronic Structures of the Dithiolate Zn and Ni
Complexes. The L€owdin population analysis of complexes 1*
and 2* is presented in Table 5. In the [ZnL] complex, the
HOMO, nearly degenerate with the HOMOꢀ1, is almost
exclusively localized on the two thiolate sulfur atoms (36% for
each), while for the [NiL] complex it also contains significant
metal character (40% on Ni and 24% on each sulfur atom)
(Figure 5). The π-antibonding nature of the HOMO found in 2*
and other Ni thiolate complexes has been previously used as the
rationale for the increased nucleophilicity of the coordinated
thiolates.42 In 1*, the strong ionic character of the ZnꢀS bond
compensates for the absence of the antibonding interactions,
leading to a Zn complex which is just as nucleophilic as the Ni
complex.14 It is expected that these subtle electronic effects can
be obtained from evaluation of the molecular electrostatic
potential (MESP) around the lone pair region of the thiolate
sulfur. Local minima of the MESP, denoted hereafter Vmin, are
usually observed in these regions where the electronic term
dominates over the nuclear term. Determining MESP represents
an interesting approach to assess the molecule’s reactivity toward
positively or negatively charged reactants, because it provides a
good view of the relative polarity of a molecule. For both 1* and 2*,
While the product arising from the mono-S-methylation of
the Ni complex, 2Me, has been isolated and characterized by
X-ray crystallography, for the Zn complex, the rate of the second
S-methylation in the Zn complex is too fast to isolate the mono-
S-methylated Zn product. DFT calculations were thus used to
predict the corresponding structure. Two optimized structures
have been obtained. First, optimization has been initiated from
the X-ray data of 2Me, in which the NiII ion has been substituted
by ZnII, and is denoted 1Me(C)* (for the closed form). The
second optimized structure is issued from the X-ray structure of
1Me2 and is denoted 1Me(O)* (for the open form). The two
structures have been conserved for the discussion since the
difference in energy between these two structures is less than
1 kcal/mol and the energy barrier between them is also very
small, meaning that both structures can be present in solution.
The principal structural features of the DFT-optimized structure
of 1Me(C)*, 1Me(O)*, and 2Me* are given in Table 4. For 2Me*, the
calculated structure compared well with the experimental data,
unambiguously demonstrating that the thioether remains coor-
dinated to the NiII center. Conversely for 1Me(C)*, the long
ZnꢀSMe distance (2.817 Å) shows that this ligand is dissociated
10051
dx.doi.org/10.1021/ic200899w |Inorg. Chem. 2011, 50, 10047–10055

Inorganic Chemistry
ARTICLE
Table 6. Wiberg Bond Indices Calculated for the Me-
talꢀSulfur Bonds for Complexes 1*, 1Me(C)*, 1Me(O)*, 2*,
and 2Me
*
Wiberg bond
index
complexes
bond
1*
1Me(C)
ZnꢀSthiolate
ZnꢀSthiolate
ZnꢀSthioether
ZnꢀSthiolate
NiꢀSthiolate
NiꢀSthiolate
NiꢀSthioether
0.35
0.32
0.08
0.37
0.55
0.53
0.41
*
1Me(O)
2*
2Me
*
*
Figure 6. Electrostatic potential on the 0.02 au molecular surface
for 1Me(C)*, 1Me(O)*, and 2Me*.
than that of 2Me* and similar to that of 1* (ꢀ0.078 au). Conse-
quently, these calculations indicate that the negative partial charge
of the remaining thiolate sulfur is also partly quenched for the Ni
complex compared to the Zn one.
from the metal ion. In fact, the ZnꢀSthioether bond lengths
found in the rare examples of bound thioether Zn complexes
are in the range 2.39ꢀ2.62 Å.12,15 For 1Me(O)*, the ZnꢀN, ZnꢀI,
and ZnꢀSthiolate bond distances are comparable to that of
1
Me(C)* while the ZnꢀSthioether bond length is notably increased
leading to an open form.
The HOMOs for 1Me(C)*, 1Me(O)*, and 2Me* are displayed in
Figure 5. The HOMO of 2Me* clearly reveals the loss of anti-
bonding interactions at the NiꢀSMe bond, and the contribution
of the thioether sulfur atom to the HOMO becomes negligible
(1%). However, the contribution of the thiolate sulfur atom to
the HOMO in 2Me* is still significant (18%) and cannot explain
the lack of reactivity of the complex. Looking at 1Me(C)* and
’ CONCLUDING REMARKS
The reactivity of mononuclear dithiolate N2S2 Ni and Zn
complexes toward S-methylation was investigated by kinetic
studies, and the results were tentatively rationalized by means
of S K-edge XAS measurements combined with quantum
chemistry. In the presence of an excess of CH3I, a double
S-methylation occurs in the case of the Zn complex, while for
the Ni complex, only the mono-S-methylated product is formed
at room temperature. However, the data show that a similar
mechanism is operative for the first S-methylation in both Ni and
Zn dithiolate complexes. This implicates that the nucleophilicity
of the remaining thiolate sulfur atom is different in the mono-
S-methylated Ni and Zn complexes. Besides, in the case of the Zn
complex, the mono-S-methylated complex cannot be isolated
given that the second reaction is faster than the first one.
The S K-edge XAS measurements show, as expected, that the
NiꢀSthiolate bond is highly covalent, while the character of the
ZnꢀSthiolate bond appears to be ionic. However, evaluation of the
minimum of the electrostatic potential of the thiolate sulfurs in
both 1 and 2 complexes shows that their nucleophilicity is
comparable, in agreement with the kinetic experiments. Regard-
ing the second S-methylation process, which only occurs for the
Zn complex, the difference in reactivity with the Ni complex can
be rationalized by molecular electrostatic potential analysis.
Indeed, this analysis suggests (i) that the nucleophilicity of the
remaining thiolate in the Ni complex is partly quenched while it is
conserved in the case of the Zn complex and, more importantly,
(ii) that the accessibility for the methyl transfer agent to the
remaining thiolate is favored for the mono-S-methylated Zn
complex compared to the Ni one.
1
Me(O)*, the thiolate sulfur atom mostly contributes to the
HOMOs (68% and 70%, respectively), explaining that the
second S-methylation occurs more rapidly than the first one.
The Wiberg bond indices calculated for all complexes (Table 6)
reveal that the strength of the bonds varies in the order NiꢀSthiolate g
NiꢀSthioether g ZnꢀSthiolate . ZnꢀSthioether. The small value
calculated for the Wiberg bond index of the ZnꢀSthioether bond
in 1Me(C)* is consistent with dissociation of the sulfur atom from
the Zn center. For the thiolate ligands, the interaction with the
central Ni is slightly stronger than with Zn, as indicated by the
increased Wiberg bond indices. On the other hand, the strengths
of the NiꢀSthioether and NiꢀSthiolate bonds are similar, in agreement
with comparable bond lengths (2.201 and 2.217 Å, respectively).
Finally, no significant effect on the MꢀSthiolate bond in 1Me(C)*,
1
Me(O)*, and 2Me* is observed upon S-alkylation.
Natural population analysis (NPA) shows that the thiolate sulfur
atom bears most of the negative charge in the complexes (ꢀ0.52,
ꢀ0.50, and ꢀ0.20 for 1Me(C)*, 1Me(O)*, and 2Me*, respectively)
(Table 5). We notice an increase of the negative charge compared
to that of the initial complexes (ꢀ0.48 and ꢀ0.14 for 1* and 2*,
respectively). At first glance, this result is in contradiction with the
fact that no second S-methylation occurs with Ni. However,
looking at the molecular electrostatic potential maps displayed in
Figure 6, it clearly appears that the accessibility for the methyl
This work represents a nice example to show how powerful
the combination of experimental and theoretical investigation is
to understand the relation between the reactivity and the
electronic structure of transition metal ion complexes.
transfer agent to the remaining thiolate is favored for 1MeO
*
compared to 1Me(C)* and 2Me*. The difference in steric hindrance
is certainly an important factor to explain why a second S-methyla-
tion can occur in 1 and not in 2. Furthermore, in the case of 2Me*,
we find a magnitude for the minimum of the electrostatic potential
of ꢀ0.052 au around the lone pair of the remaining thiolate sulfur
atom, notably reduced with respect to that of 2* (ꢀ0.069 au). In
’ EXPERIMENTAL SECTION
the case of the Zn complex, Vmin is equal to ꢀ0.069 au for 1Me(C)
*
General. The ligand H2L54 and complexes [NiL] (2)38 and [NiLMe]I
and ꢀ0.075 au for 1Me(O)*, suggesting that the open form is the
(2
were freshly distilled (over Na/benzophenone and CaH2, respectively)
)
Me 39 were prepared according to reported methods. THF and CH2Cl2
one that reacts with CH3I. The Vmin magnitude of 1Me(O)* is higher
10052
dx.doi.org/10.1021/ic200899w |Inorg. Chem. 2011, 50, 10047–10055

Inorganic Chemistry
ARTICLE
prior to use. All other reagents and solvents were used as received.
Synthesis of [ZnL] (1) was performed under argon (Schlenk techniques).
Synthesis of [ZnL] (1). Solid NaH (60% in mineral oil, 12.8 mg,
0.320 mmol) was added to a solution of H2L (100 mg, 0.128 mmol) in
THF (15 mL). After 20 min, the excess of NaH was filtered off and a
solution of Zn(OCOCH3)2 (24 mg, 0.131 mmol) in MeOH:THF 1:4
(5 mL) was added, yielding a clear yellow precipitate. After 1 h, the
solvents were removed in vacuo and the product was extracted from the
residue with CH2Cl2 (35 mL). CH2Cl2 was then removed in vacuo, and
the residual solid was washed with CH3OH (3 ꢁ 5 mL) and recrys-
tallized from CH2Cl2:CH3OH 2:1, yielding a clear yellow microcrystal-
line solid (65 mg, 0.101 mmol, 79% yield). IR (cmꢀ1): 3055w, 3024w,
2923w, 1598s, 1574m, 1487m, 1441m, 1268w, 1175w, 1078w, 1035w,
(only in the case of MeI for 15 h) of reaction in positive ionization mode
by direct perfusion in the ESI-MS interface after dilution to 5 ꢁ 10ꢀ5 M
with MeCN. All instrumental parameters remained unchanged for all
measurements (ESI capillary voltage 2 kV, sampling cone voltage 40 V).
ESI-MS (m/z, I%) of 1 + MeI: after 3 min 643.1, 100 [ZnLH]+, 579.5,
90 [LH]+; after 6 and 15 h 609.1, 100 [LMe2H]+, 671.1, 5 [ZnLMe2H]+
(see Figure S2, Supporting Information). ESI-MS (m/z, I%) of 2 + MeI:
after 3 min and 6 and 15 h: 651.1, 100 [NiLMe]+ (see Figure S2, Sup-
porting Information). ESI-MS (m/z, I%) of 1 + Me3OBF4: after 3 min
and 6 h 581.1, 100 [LH3]+. ESI-MS (m/z, I%) of 2+Me3OBF4: after 3
min 637.2, 100 [NiLH]+; after 6 h 637.2, 100 [NiLH]+, 651.4, 20
[NiLMe]+.
S K-Edge XAS. All data were measured at the Stanford Synchrotron
Radiation Lightsource under ring conditions of 3.0 GeV and 60ꢀ
100 mA. S K-edge data were measured using beamline 4-3. A fully
tuned Si(111) monochromator was utilized for energy selection, and a
Ni-coated mirror was utilized for rejection of higher harmonics. All
samples were measured at room temperature as fluorescence spectra
using a Lytle detector. Samples were ground finely and dispersed as
thinly as possible on Mylar tape to minimize the possibility of fluores-
cence saturation effects. Data represent 2ꢀ3 scan averages. All samples
were monitored for photoreduction throughout the course of data
collection. The S K-edge energy was calibrated using the S K-edge
1
1022w, 804w, 793w, 754w, 742m, 695s, 592 m. H NMR (500 MHz,
CDCl3): δ 3.97 (s, 4H, CH2), 6.60 (d, J = 7.7 Hz, 2H, CH bpy), 7.10
(m, 12H, CH Ph), 7.36 (d, J = 7.6 Hz, 8H, CH Ph), 7.60 (t, J = 7.8 Hz,
2H, CH bpy), 7.90 (d, J = 7.8 Hz, 2H, CH bpy). ESI-MS (10ꢀ5 M,
CH2Cl2:CH3CN, m/z, I%): 643.1, 100 [ZnLH]+. Anal. Calcd for
C38H30N2S2Zn (644.17): C, 70.85; H, 4.69; N, 4.35. Found: C, 70.93;
H, 4.61; N, 4.28. Colorless X-ray suitable single crystals of 1 were obtained
by layering CH3OH over a saturated solution of the product in CH2Cl2.
Obtaining of Single X-ray Crystals of [ZnLMe2I2] (1Me2).
Colorless single crystals of [ZnLMe2I2] (1Me2) were obtained by slow
evaporation of a CH2Cl2:CH3OH (1:1) solution of [ZnL], which was
previously treated with CH3I (20 equiv) in CH2Cl2 for 12 h. 1H NMR
(500 MHz, CDCl3): δ 1.87 (s, 6H, CH3), 4.93 (s, 4H, CH2), 7.21 (t, J =
7.3 Hz, 4H, CH Ph), 7.34 (t, J = 7.7 Hz, 8H, CH Ph), 7.61 (d, J = 8.0 Hz,
2H, CH bpy), 7.66 (d, J = 7.8 Hz, 8H, CH Ph), 7.76 (t, J = 8.0 Hz, 2H,
CH bpy), 7.90 (d, J = 7.9 Hz, 2H, CH bpy).
spectra of Na2S2O3 5H2O, run at intervals between sample scans. The
3
maximum of the first pre-edge feature in the spectrum was fixed at
2472.02 eV. A step size of 0.08 eV was used over the edge region. Data
were averaged, and a smooth background was removed from all spectra
by fitting a polynomial to the pre-edge region and subtracting this
polynomial from the entire spectrum. Normalization of the data was
accomplished by fitting a flattened polynomial or straight line to the
postedge region and normalizing the postedge to 1.0.
Physical Measurements. The infrared spectrum of 1 was recorded
on a Magna-IR TM 550 Nicolet spectrometer as a KBr pellet. 1H NMR
spectra were recorded on a Varian Unity+ 500 MHz spectrometer.
Elemental analysis of 1 was carried out with a C, H, N analyzer (SCA,
CNRS).
X-ray Crystallography. A summary of data collection and struc-
ture refinement for 1 and 1Me2 is reported in Table S1, Supporting
Information. Single-crystal diffraction data of 1 were taken using a
Bruker AXS Enraf-Nonius Kappa CCD diffractometer. The molecular
structure was solved by direct methods and refined with the TEXSAN
software package. Single-crystal diffraction data of 1Me2 were taken using
an Oxford-Diffraction Xcallibur S Kappa geometry diffractometer (Mo
Kα radiation, graphite monochromator, λ 0.71073 Å) at 150 K. An
absorption correction was applied using the ABSPACK Oxford-diffrac-
tion program55 with transmission factors in the range from 0.623 to
0.940. The molecular structure of 1Me2 was solved by direct methods and
refined on F2 by full matrix least-squares techniques using the SHELXTL
package.56 All non-hydrogen atoms were refined anisotropically, and
hydrogen atoms were placed at their calculated position.
Electrochemistry. Electrochemical measurements were carried
out under an argon atmosphere (in glovebox at room temperature).
Cyclic voltammetry experiments were performed by using an EG&G
model 173 potentiostat/galvanostat equipped with a PAR model uni-
versal programmer. A standard three-electrode electrochemical cell was
used. Potentials were referred to an Ag/0.01 M AgNO3 reference
electrode in CH3CN + 0.1 M Bu4NClO4. Measured potentials were
calibrated through the use of an internal Fc/Fc+ standard. The working
electrode was a vitreous carbon disk (3 mm in diameter) polished with 2
Kinetic Measurements. For reactions of 1 and 2 with CH3I, the
1
rates of the first S-methylation process were measured by H NMR
spectroscopy in pseudo-first-order conditions (i.e., in the presence of a
fixed concentration of complex and a large excess of CH3I) by moni-
toring the decay of the resonances of the initial complexes (in both cases
the CH2 singlet of the coordinated ligand L2ꢀ) as a function of time.
Standard solutions of the complexes (1.3 mM of 1, 1.6 mM of 2) and
CH3I (0.80 and 6.96 M) were prepared in CDCl3 and stored at 4 ꢀC in
the dark. The reagents (and further CDCl3) were combined in a NMR
sample tube immediately prior to measurements (final concentrations
1.1 mM of 1 + 33ꢀ522 mM range of CH3I, 1.4 mM of 2 + 5ꢀ80 mM
range of CH3I). After being mixed thoroughly, the tube was placed in a
1
thermostat probe of an NMR spectrometer. H NMR spectra were
recorded throughout the reaction. The integrated intensities I of the
CH2 singlet at 3.9 and 4.1 ppm for 1 and 2, respectively, provide a
relative measurement of the concentration of the initial complex in each
spectrum. Pseudo-first-order rate constants (kobs) were determined
from the slopes of first-order plots, ꢀln I versus time (Tables S2ꢀS9,
Supporting Information), at different analytical concentrations of CH3I
and temperatures (285.4, 294.0, 302.5, 311.1 K). Second-order rate
constants k2 were determined using the relationship kobs = k2[CH3I] for
each temperature (Table 2). An Eyring analysis of the temperature
dependence of k2 yielded activation parameters ΔHq and ΔSq
(Figure 2).
μm diamond paste (Mecaprex Presi) for cyclic voltammetry (Ep , anodic
a
peak potential; Ep , cathodic peak potential; E1/2 = (Ep + Ep )/2; ΔEp =
a
c
Ep ꢀ Ep ). The cauxiliary electrode was a Pt wire in DMF + 0.1 M
a
c
Bu4NPF6 solution.
ESI-MS Experiments. ESI-MS experiments were performed on a
Bruker Esquire 3000 Plus ion trap spectrometer equipped with an
electrospray ion source (ESI). Samples were prepared at 30 ꢀC by
mixing 5 mL of a solution of 1 or 2 (0.6 mM of in CH2Cl2) with 20 equiv
(200 μL) of a solution of MeI or Me3OBF4 (0.63 M in MeOH:CH2Cl2
1:9). The solutions have been analyzed after 3 min and 6 and 15 h
Computational Details. All calculations were performed with the
ORCA quantum chemistry program package.57 Geometry optimizations
were carried out using the BP86 functional,58,59 the zeroth-order regular
approximation for relativistic effects (ZORA),60,61 and the scalar relati-
vistic recontraction of the def2-TZVP basis sets.62 In all calculations we
took advantage of the RI approximation using the Coulomb-fitting basis
10053
dx.doi.org/10.1021/ic200899w |Inorg. Chem. 2011, 50, 10047–10055

Inorganic Chemistry
ARTICLE
set of Weigend.63 A dense integration grid was used (ORCA grid4),
coupled with tight SCF convergence criteria.
XAS spectra were calculated by employing time-dependent density
functional theory (TD-DFT) on the optimized geometries, as detailed
previously.51 These calculations were done analogously to the geometry
optimizations, with the sole exception of uncontracting the density-
fitting basis set.
The local minimum of the molecular electrostatic potential (MESP)
around the lone pair region of the sulfur thiolate atom was determined
by employing a grid search technique on a cubic grid (width 101 points/
side).
(16) Morlok, M. M.; Janak, K. E.; Zhu, G.; Quarless, D. A.; Parkin, G.
J. Am. Chem. Soc. 2005, 127, 14039.
(17) Ji, M.; Benkmil, B.; Vahrenkamp, H. Inorg. Chem. 2005, 44, 3518.
(18) Ibrahim, M. M.; He, G.; Seebacher, J.; Benkmil, B.;
Vahrenkamp, H. Eur. J. Inorg. Chem. 2005, 2005, 4070.
(19) Rombach, M.; Seebacher, J.; Ji, M.; Zhang, G. F.; He, G. S.;
Ibrahim, M. M.; Benkmil, B.; Vahrenkamp, H. Inorg. Chem. 2006, 45, 4571.
(20) Melnick, J. G.; Zhu, G.; Buccella, D.; Parkin, G. J. Inorg. Biochem.
2006, 100, 1147.
(21) Notni, J.; G€unther, W.; Anders, E. Eur. J. Inorg. Chem. 2007,
2007, 985.
(22) Wilker, J. J.; Wetterhahn, K. E.; Lippard, S. J. Inorg. Chem. 1997,
36, 2079.
(23) Brand, U.; Rombach, M.; Seebacher, J.; Vahrenkamp, H. Inorg.
Chem. 2001, 40, 6151.
(24) Chiou, S. J.; Riordan, C. G.; Rheingold, A. L. Proc. Natl. Acad.
Sci. U.S.A. 2003, 100, 3695.
(25) Bridgewater, B. M.; Fillebeen, T.; Friesner, R. A.; Parkin, G.
J. Chem. Soc., Dalton Trans. 2000, 4494.
(26) Chiou, S.-J.; Innocent, J.; Riordan, C. G.; Lam, K.-C.;
Liable-Sands, L.; Rheingold, A. L. Inorg. Chem. 2000, 39, 4347.
(27) Kaasjager, V. E.; Bouwman, E.; Gorter, S.; Reedijk, J.; Grapperhaus,
C. A.; Reibenspies, J. H.; Smee, J. J.; Darensbourg, M. Y.; Derecskei-Kovacs,
A.; Thomson, L. M. Inorg. Chem. 2002, 41, 1837.
’ ASSOCIATED CONTENT
Supporting Information. Cif files of 1 and 1Me2; addi-
S
b
tional structural, electrochemical, and S K-edge XAS data; com-
plementary data on kinetic investigations; further computational
details. This material is available free of charge via the Internet at
http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: carole.duboc@ujf-grenoble.fr.
(28) Maroney, M. J.; Choudhury, S. B.; Bryngelson, P. A.; Mirza,
S. A.; Sherrod, M. J. Inorg. Chem. 1996, 35, 1073.
(29) Henderson, R. K.; Bouwman, E.; Spek, A. L.; Reedijk, J. Inorg.
Chem. 1997, 36, 4616.
’ ACKNOWLEDGMENT
(30) Mullins, C. S.; Grapperhaus, C. A.; Frye, B. C.; Wood, L. H.;
Hay, A. J.; Buchanan, R. M.; Mashuta, M. S. Inorg. Chem. 2009, 48, 9974.
(31) Chohan, B. S.; Maroney, M. J. Inorg. Chem. 2006, 45, 1906.
(32) Farmer, P. J.; Reibenspies, J. H.; Lindahl, P. A.; Darensbourg,
M. Y. J. Am. Chem. Soc. 1993, 115, 4665.
M.G. thanks the CNRS for his postdoctoral fellowship. The
authors thank B. Gerey for his participation to some experiments.
S.D. acknowledges Cornell University for financial support.
Portions of the data in this paper were obtained at SSRL.
SSRL operations are funded by the Department of Energy,
Office of Basic Energy Sciences. The Structural Molecular
Biology program is supported by the National Institutes of
Health (grant 5 P41 RR001209), National Center for Research
Resources, Biomedical Technology Program, and Department of
Energy, Office of Biological Environmental Research.
(33) Musie, G.; Reibenspies, J. H.; Darensbourg, M. Y. Inorg. Chem.
1998, 37, 302.
(34) Bellefeuille, J. A.; Grapperhaus, C. A.; Derecskei-Kovacs, A.;
Reibenspies, J. H.; Darensbourg, M. Y. Inorg. Chim. Acta 2000, 300ꢀ302, 73.
(35) Green, K. N.; Brothers, S. M.; Jenkins, R. M.; Carson, C. E.;
Grapperhaus, C. A.; Darensbourg, M. Y. Inorg. Chem. 2007, 46, 7536.
(36) Smee, J. J.; Miller, M. L.; Grapperhaus, C. A.; Reibenspies, J. H.;
Darensbourg, M. Y. Inorg. Chem. 2001, 40, 3601.
(37) Grapperhaus, C. A.; Kreso, M.; Burkhardt, G. A.; Roddy,
J. V. F.; Mashuta, M. S. Inorg. Chim. Acta 2005, 358, 123.
(38) Gennari, M.; Orio, M.; Pꢀecaut, J.; Neese, F.; Collomb, M.-N.;
Duboc, C. Inorg. Chem. 2010, 49, 6399.
’ REFERENCES
(1) Solomon, E. I.; Gorelsky, S. I.; Dey, A. J. Comput. Chem. 2006,
27, 1415.
(39) Gennari, M.; Orio, M.; Pꢀecaut, J.; Bothe, E.; Neese, F.;
Collomb, M.-N.; Duboc, C. Inorg. Chem. 2011, 50, 3707.
(40) Gennari, M.; Pꢀecaut, J.; DeBeer, S.; Neese, F.; Collomb, M.-N.;
Duboc, C. Angew. Chem., Int. Ed. 2011, 50, 5662.
(41) Alves de Sousa, R.; Galardon, E.; Rat, M.; Giorgi, M.; Artaud, I.
J. Inorg. Biochem. 2005, 99, 690.
(2) Kovacs, J. A. Chem. Rev. 2004, 104, 825.
(3) Venkateswara Rao, P.; Holm, R. H. Chem. Rev. 2003, 104, 527.
(4) Wuerges, J.; Lee, J.-W.; Yim, Y.-I.; Yim, H.-S.; Kang, S.-O.;
Djinovic Carugo, K. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 8569.
(5) Grapperhaus, C. A.; Darensbourg, M. Y. Acc. Chem. Res. 1998,
31, 451.
(42) Grapperhaus, C. A.; Mullins, C. S.; Kozlowski, P. M.; Mashuta,
M. S. Inorg. Chem. 2004, 43, 2859.
(6) Peariso, K.; Zhou, Z. H. S.; Smith, A. E.; Matthews, R. G.;
Penner-Hahn, J. E. Biochemistry 2001, 40, 987.
(43) Seebacher, J.; Ji, M.; Vahrenkamp, H. Eur. J. Inorg. Chem.
2004, 409.
(44) Potenza, M. N.; Stibrany, R. T.; Potenza, J. A.; Schugar, H. J.
Acta Crystallogr. 1992, 48, 454.
(7) Tobin, D. A.; Pickett, J. S.; Hartman, H. L.; Fierke, C. A.;
Penner-Hahn, J. E. J. Am. Chem. Soc. 2003, 125, 9962.
(8) Myers, L. C.; Terranova, M. P.; Ferentz, A. E.; Wagner, G.;
Verdine, G. L. Science 1993, 261, 1164.
(45) Lindoy, L. F.; Lip, H. C.; Rea, J. H.; Smith, R. J.; Henrick, K.;
McPartlin, M.; Tasker, P. A. Inorg. Chem. 1980, 19, 3360.
(46) Shadle, S. E.; Pennerhahn, J. E.; Schugar, H. J.; Hedman, B.;
Hodgson, K. O.; Solomon, E. I. J. Am. Chem. Soc. 1993, 115, 767.
(47) Shadle, S. E.; Hedman, B.; Hodgson, K. O.; Solomon, E. I. J. Am.
Chem. Soc. 1995, 117, 2259.
(48) Solomon, E. I.; Hedman, B.; Hodgson, K. O.; Dey, A.; Szilagyi,
R. K. Coord. Chem. Rev. 2005, 249, 97.
(49) Solomon, E. I.; Penfield, K. W.; Gewirth, A. A.; Lowery, M. D.;
Shadle, S. E.; Guckert, J. A.; LaCroix, L. B. Inorg. Chim. Acta 1996,
243, 67.
(9) Wilker, J. J.; Lippard, S. J. J. Am. Chem. Soc. 1995, 117, 8682.
(10) Wilker, J. J.; Lippard, S. J. Inorg. Chem. 1997, 36, 969.
(11) Grapperhaus, C. A.; Tuntulani, T.; Reibenspies, J. H.;
Darensbourg, M. Y. Inorg. Chem. 1998, 37, 4052.
(12) Hammes, B. S.; Carrano, C. J. Inorg. Chem. 2001, 40, 919.
(13) Warthen, C. R.; Hammes, B. S.; Carrano, C. J.; Crans, D. C.
J. Biol. Inorg. Chem. 2001, 6, 82.
(14) Fox, D. C.; Fiedler, A. T.; Halfen, H. L.; Brunold, T. C.; Halfen,
J. A. J. Am. Chem. Soc. 2004, 126, 7627.
(15) Grapperhaus, C. A.; Mullins, C. S.; Mashuta, M. S. Inorg. Chim.
Acta 2005, 358, 623.
10054
dx.doi.org/10.1021/ic200899w |Inorg. Chem. 2011, 50, 10047–10055

Inorganic Chemistry
ARTICLE
(50) Dey, A.; Green, K. N.; Jenkins, R. M.; Jeffrey, S. P.; Darensbourg,
M.; Hodgson, K. O.; Hedman, B.; Solomon, E. I. Inorg. Chem. 2007,
46, 9655.
(51) DeBeer George, S.; Neese, F. Inorg. Chem. 2010, 49, 1849.
(52) DeBeer George, S.; Petrenko, T.; Neese, F. Inorg. Chim. Acta
2008, 361, 965.
(53) In the case of 2 and 2Me, the lowest unoccupied molecular
orbital with sulfur and nickel character is actually the LUMO+1.
(54) Kopf, M. A.; Varech, D.; Tuchagues, J. P.; Mansuy, D.; Artaud, I.
J. Chem. Soc., Dalton Trans. 1998, 991.
(55) ABSPACK; Oxford Diffraction Ltd: Abingdon, Oxfordshire,
England, 2010.
(56) Sheldrick, G. M. SHELXTL; Madison, WI, 1998.
(57) Neese, F. ORCA; Universit€at Bonn: Bonn, Germany, 2007.
(58) Becke, A. D. Phys. Rev. A 1988, 38, 3098.
(59) Perdew, J. P. Phys. Rev. B 1986, 33, 8822.
(60) van W€ullen, C. J. Chem. Phys. 1998, 109, 392.
(61) van Lenthe, E.; Snijders, J. G.; Baerends, E. J. J. Chem. Phys.
1996, 105, 6505.
(62) Pantazis, D. A.; Chen, X. Y.; Landis, C. R.; Neese, F. J. Chem.
Theory Comput. 2008, 908.
(63) Weigend, F. Phys. Chem. Chem. Phys. 2006, 8, 1057.
10055
dx.doi.org/10.1021/ic200899w |Inorg. Chem. 2011, 50, 10047–10055