Thioether ligation in Co(III) complexes with carboxamido nitrogens as donors: Implications on the coordination structure of the cobalt site in nitrile hydratase

Article abstract of DOI:10.1016/S0020-1693(01)00523-0

In order to determine the role of the sulfur donors around the Co(III) site of the enzyme nitrile hydratase, we have synthesized a designed ligand PyPSMeH₂ (Hs are dissociable carboxamide hydrogens) with carboxamido nitrogens and thioether sulfur donors. Although Co(III) complexes with bound thioether groups have previously been synthesized with other ligands, attempts to synthesize such a species with PyPSMe^2- have failed. The only complex isolated is the bis complex (Et₄N)[Co(PyPSMe)₂] (1) in which the potentially pentadentate PyPSMe^2- ligand acts as tridentate and all four thioether sulfurs remain as pendant groups. In 1, one of the four carboxamido groups is O-bonded. Methylation of the analogous (Et₄N)[Co₂(PyPS)₂] with iodomethane affords (Et₄N)[Co₂(PyPS(SMe))₂] (2), the only Co(III) complex with weakly bound thioether groups. The dimeric complex 2 contains two bridging thiolato sulfurs and each Co(III) center has one bound thioether sulfur in its coordination sphere. These two terminal thioether groups of 2 are replaced easily by other ligands like pyridine. Reaction of CN^- with 2 affords the dicyano complex (Et₄N)₂[Co(PyPS(SMe)(CN)₂] (3) with pendant thioether group. Collectively, these results indicate that Co(III) centers with coordinated carboxamido nitrogen(s) exhibit very low affinity toward thioether sulfur.

Full text of DOI:10.1016/S0020-1693(01)00523-0

www.elsevier.com/locate/ica
Inorganica Chimica Acta 321 (2001) 135–141
Thioether ligation in Co(III) complexes with carboxamido
nitrogens as donors: implications on the coordination structure of
the cobalt site in nitrile hydratase
Laurie A. Tyler a, Marilyn M. Olmstead b, Pradip K. Mascharak a,*
a Department of Chemistry and Biochemistry, Uni6ersity of California, Santa Cruz, CA 95064, USA
b Department of Chemistry, Uni6ersity of California, Da6is, CA 95616, USA
Received 11 May 2001; accepted 8 June 2001
Abstract
In order to determine the role of the sulfur donors around the Co(III) site of the enzyme nitrile hydratase, we have synthesized
a designed ligand PyPSMeH2 (Hs are dissociable carboxamide hydrogens) with carboxamido nitrogens and thioether sulfur
donors. Although Co(III) complexes with bound thioether groups have previously been synthesized with other ligands, attempts
to synthesize such a species with PyPSMe2− have failed. The only complex isolated is the bis complex (Et4N)[Co(PyPSMe)2] (1)
in which the potentially pentadentate PyPSMe2− ligand acts as tridentate and all four thioether sulfurs remain as pendant groups.
In 1, one of the four carboxamido groups is O-bonded. Methylation of the analogous (Et4N)[Co2(PyPS)2] with iodomethane
affords (Et4N)[Co2(PyPS(SMe))2] (2), the only Co(III) complex with weakly bound thioether groups. The dimeric complex 2
contains two bridging thiolato sulfurs and each Co(III) center has one bound thioether sulfur in its coordination sphere. These
two terminal thioether groups of 2 are replaced easily by other ligands like pyridine. Reaction of CN− with 2 affords the dicyano
complex (Et4N)2[Co(PyPS(SMe)(CN)2] (3) with pendant thioether group. Collectively, these results indicate that Co(III) centers
with coordinated carboxamido nitrogen(s) exhibit very low affinity toward thioether sulfur. © 2001 Elsevier Science B.V. All
rights reserved.
Keywords: Thioether ligation; Carboxamido nitrogens; Nitrile hydratase
1. Introduction
unmodified thiolate positioned trans to the active site.
The post-translational oxidation of the CysꢀS centers
has recently been shown to be essential for the activity
of the Fe-containing enzyme [8] although their specific
function is not understood at this time. The unprece-
dented coordination sphere around the Fe(III) center is
thought to play a crucial role in the catalytic activity of
the NHases. To date, no crystallographic study has
been reported for a Co-containing NHase. High se-
quence homologies at the active sites of Fe–NHase and
Co–NHase and spectroscopic evidences, however, sug-
gest that the coordination structure of the Co(III)
center in Co–NHase is very similar to that of Fe(III) in
Fe–NHase [9,10]. The mechanism by which NHases
hydrolyze nitriles is elusive at this time.
The enzyme nitrile hydratase (NHase), involved in
the assimilation of organic nitriles by various microor-
ganisms, contains either a low-spin Fe(III) or Co(III)
metal center at its active site and catalyzes the conver-
sion of a variety of nitrile substrates to the correspond-
ing amides [1–5]. Recent crystallographic studies of two
Rhodococcus NHases have revealed a single low-spin
Fe(III) metal center coordinated to two deprotonated
carboxamido nitrogens and three CysꢀS centers [6] two
of which are modified to Cys-sulfenic and -sulfinic
groups [7]. The thiolates are ligated in a fac arrange-
ment around the Fe(III) center in the enzyme with the
Recently we reported the first functional model of the
Co(III) site of Co–NHase which catalyzes the hydra-
tion of acetonitrile to acetamide under mild conditions
* Corresponding author. Tel.: +1-831-459-4251; fax: +1-831-459-
2935.
E-mail address: pradip@chemistry.ucsc.edu (P.K. Mascharak).
0020-1693/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved.
PII: S0020-1693(01)00523-0

136
L.A. Tyler et al. / Inorganica Chimica Acta 321 (2001) 135–141
[11]. The functional model complex contains a Co(III)
metal center ligated to a pentacoordinate ligand,
PyPSH4, which contains two deprotonated peptide ni-
trogens, two thiolates and a pyridine nitrogen.
pyridine and 1-methylimidazole and the reaction of 2
with CN− affords the dicyano complex (Et4N)2-
[Co(PyPS(SMe))(CN)2] (3) with pendant thioether
group. Therefore the results indicate that thioether
groups are not good ligands for Co(III) when addi-
tional carboxamido groups are present in the coordina-
tion sphere. And finally, we report that none of the
Co(III) complexes with thioether groups (bound or
unbound) promote hydrolysis of nitriles.
In order to investigate the importance of the thiolato
sulfur groups in the reactivity of our model complex,
we have now synthesized the ligand PyPSMeH2 (the
two dissociable carboxamido protons are denoted by
H2) which is identical to PyPSH4 except for the two
thiolates being replaced with methyl thioether groups.
A close scrutiny of the literature reveals that no Co(III)
complex containing thioether and carboxamido groups
has been reported so far and hence the reactivity of
such a species is unknown. Since the spectroscopic
parameters of Co(III) complexes with thiolato and
thioether sulfurs are often very similar [12,13], one
expects that the reactivity of such complexes could be
similar.
2. Experimental
2.1. Materials
2,6-Pyridinedicarbonyl dichloride, 2-(methylthio)-
aniline, sodium hydride, triethylamine, iodomethane
and tetraethylammonium cyanide were purchased from
Aldrich Chemical Co. and used without further purifi-
cation. [Co(NH3)5Cl]Cl2 was synthesized by following
the published procedure [14]. All manipulations were
carried out using standard Schlenk techniques except
otherwise noted and the solvents were dried and dis-
tilled before use.
2.2. Physical measurements
In this paper, we report that the reaction of
PyPSMe2− (deprotonated PyPSMeH2) with Co(III) af-
fords the bis complex (Et4N)[Co(PyPSMe)2] (1) with
four pendant thioether moieties. In addition, attempts
to synthesize a Co(III) complex with bound thioether
sulfur via the reaction of iodomethane with the previ-
ously reported model complex (Et4N)2[Co(PyPS)(CN)]
have so far afforded no characterizable Co(III) species.
The only Co(III) complex with bound thioether sulfurs
that we have isolated so far is the dimeric species
[Co2(PyPS(SMe))2] (2), which is obtained in the reac-
tion of iodomethane with the previously reported
dimeric complex (Et4N)2[Co2(PyPS)2]. However, we
have also noted that the ligated thioether groups in 2
can be displaced easily by weak nucleophiles including
Infrared spectra were obtained with a Perkin–Elmer
1600 FTIR spectrophotometer. Absorption spectra
were measured on a Perkin–Elmer Lambda 9 spec-
1
trophotometer. H NMR spectra were recorded either
on a Varian Unity Plus 500 running Solaris 2.6/VNMR
6.1B or a Bruker 250 MHz spectrometer with a Tec-
Mag workstation upgrade.
2.3. Preparation of compounds
The ligand PyPSH4, and the two complexes reported,
(Et4N)2[Co2(PyPS)2] and (Et4N)2[Co(PyPS)CN], were
synthesized by following published procedures [11,15].
2.3.1. Preparation of PyPSMeH2
A batch of 205 mg (1.03 mmol) of 2,6-pyridinedicar-
bonyl dichloride was dissolved in 20 ml of chloroform
with 8 ml of Et3N. To this solution, 1.27 ml (10.12
mmol) of 2-(methylthio)aniline was added and the solu-
tion was stirred for 2 days. The solvent was then
removed by rotary evaporation and the yellow–green
solid was washed two times with 30 ml of THF. The
solid was then extracted into 50 ml of chloroform and
layered with 20 ml of Et2O and kept at −28 °C for 24
h. The light yellow crystalline material thus obtained
was collected and dried under high vacuum for 10 h.
Yield: 0.95 g (46%). 1H NMR (CDCl3, 250 MHz,
25 °C, l from TMS): 2.40 (s, 3H, SMe), 7.18 (t, 1H),
7.36 (t, 1H), 8.17 (t, 1H), 8.35 (d, 1H), 8.53 (d, 2H)

L.A. Tyler et al. / Inorganica Chimica Acta 321 (2001) 135–141
137
10.58 (s, 1H). Selected IR bands: (KBr pellet, cm−1
(wCꢁO) 1684.
)
TMS):1.20 (s, 3H), 5.48 (d, 1H), 6.52 (t, 1H), 7.13 (t,
1H), 7.24 (t, 1H), 7.47 (d, 1H), 7.55 (d, 1H), 7.63 (t,
1H), 8.06 (d, 1H), 8.17 (d, 1H), 8.45 (t, 1H), 8.57 (d,
1H). Selected IR bands: (KBr pellet, cm−1) 1623 (wCꢁO).
Electronic absorption spectrum: umax (nm) (m,
2.3.2. Synthesis of (Et4N)[Co(PyPSMe)2] (1)
A batch of 300 mg (0.74 mmol) of PyPSMeH2 was
dissolved in 10 ml of dimethylformamide (DMF) and
37 mg (1.55 mmol) of NaH was added. The solution
was stirred for 10 min. Next, a batch of 185 mg (0.74
mmol) of [Co(NH3)5Cl]Cl2 was added and the solution
was heated at 60 °C for 1.5 h. A batch of 245 mg (1.47
mmol) of (Et4N)Cl was then added to the orange
solution and the DMF was removed by vacuum distil-
lation. The solid thus obtained was dissolved in 15 ml
of acetonitrile and filtered. Acetone was slowly diffused
into this solution and the brown–orange crystals col-
lected after 48 h. Yield: 330 mg (45%). 1H NMR
(DMSO-d6, 250 MHz, 25 °C, l from TMS): 1.15 (t,
Et4N), 1.55 (s, 3H,SMe), 1.60 (s, 3H, SMe), 3.20 (q,
Et4N), 2.06 (s, 6H, SMe) 6.87 (m, 15H), 7.40 (m, 1H),
7.95 (m, 4H), 8.09 (d, 1H), 8.22 (t, 1H). Selected IR
bands: (KBr pellet, cm−1) (wCꢁO) 1618, 1590. Electronic
absorption spectrum: umax (nm) (m, M−1 cm−1) (aceto-
nitrile): 690 (95), 475 sh (2550), 405 (4600).
M
(6250).
−1 cm−1) (DMF): 575 (2400), 430 (5410), 372 sh
2.3.4. Synthesis of (Et4N)2[Co(PyPS(SMe))(CN)2] (3)
A batch of 105 mg (0.116 mmol) of 2 was suspended
in 10 ml of acetonitrile and the mixture was stirred for
10 min. Next, a batch of 106 mg (0.680 mmol) of
(Et4N)CN was added. After 2 h, the mixture became
homogeneous and a deep red–orange color developed.
The solution was filtered to remove any unreacted 2.
Et2O was allowed to slowly diffuse into this solution.
Large orange blocks were collected after 24 h. Yield: 70
1
mg (70%). H NMR (DMSO-d6, 500 MHz, 25 °C, l
from TMS): 1.13 (t, Et4N), 2.24 (s, 3H), 3.16 (q, Et4N),
6.50 (m, 2H), 6.76 (d, 1H), 6.96 (m, 3H), 7.15 (d, 1H),
7.55 (d, 1H), 7.74 (t, 1H), 8.11 (t, 1H), 8.69 (d, 1H).
Selected IR bands: (KBr pellet, cm−1) (wCꢁN) 2114,
(wCꢁO) 1597. Electronic absorption spectrum: umax (nm)
(m, M−1 cm−1) (DMF): 475 (1920), 345 (5600).
2.3.3. Synthesis of [Co2(PyPS(SMe))2] (2)
A batch of 218 mg (0.19 mmol) of (Et4N)2[Co2-
(PyPS)2] was dissolved in 15 ml of acetonitrile. To this
solution, an aliquot of 480 ml (7.71 mmol) of
iodomethane was added carefully and the solution was
stirred for 2 h after which a dark brown microcrys-
talline solid began to form. The stirring was stopped
and the mixture was allowed to stand for an additional
2 h. The microcrystalline solid thus obtained was col-
lected and washed two times with 5 ml of acetonitrile
and dried under high vacuum for 5 h. Yield: 130 mg
2.4. X-ray data collection and structure solution and
refinement
Light brown parallelepipeds of (Et4N)[Co(PyPSMe)2]
(1), suitable for X-ray analysis, were obtained by slow
diffusion of acetone into a solution of 1 in acetonitrile.
Black parallelepipeds of [Co2(PyPS(SMe))2] (2) were
obtained by slow diffusion of acetone into an acetoni-
trile solution of 2. Red plates of (Et4N)2[Co(PyPS-
(SMe))(CN)2] (3) were obtained by slow diffusion of
Et2O into a solution of 3 in acetonitrile. Diffraction
data for complexes 1–3 were collected on a Bruker
SMART 1000 diffractometer. All structures were solved
by direct methods (SHELXS-97). The data were cor-
rected for absorption effects [16]. In the structure of 1,
one pendant arm containing C36–C42 is disordered.
This fact has been omitted in Fig. 1 for sake of clarity.
Machine parameters, crystal data, and data collection
parameters are summarized in Table 1. Selected bond
distances and bond angles are listed in Table 2. The
three sets of crystallographic data have been submitted
as supporting information.
1
(75%). H NMR (DMSO-d6, 500 MHz, 25 °C, l from
3. Results and discussion
The potentially pentadentate ligand PyPSMe2− only
affords the bis complex (Et4N)[Co(PyPSMe)2] (1) even
with
a metal–ligand ratio of 1:1. Reactions of
Fig. 1. Thermal ellipsoid plot (50% probability level) of the anion of
1 showing the numbering scheme. Hydrogen atoms are omitted for
the sake of clarity.
PyPSMe2− and [Co(NH)5Cl]Cl2 in DMF always result
in the formation of the bis complex 1 in which the

138
L.A. Tyler et al. / Inorganica Chimica Acta 321 (2001) 135–141
Table 1
Summary of crystal data and intensity collection and structure refinement parameters for (Et4N)2[Co(PyPSMe)2]·acetone (1·acetone),
[Co2(PyPS(SMe))2]·1.5 acetone·0.5 MeCN (2·1.5 acetone·0.5 MeCN) and (Et4N)2[Co(PyPS(SMe))(CN)2]·MeCN (3·MeCN)
(Et4N)2[Co(PyPSMe)2·acetone [Co2(PyPS(SMe))2]·1.5 acetone·0.5MeCN (Et4N)2[Co(PS(SMe))(CN)2]·MeCN
Empirical formula
Molecular weight
Crystal color, habit
Temperature (K)
Crystal system
C53H60CoN7O5S4
1062.25
light brown parallelpiped
90(2)
C45.5H38.5Co2N6.5O5.5S4
1010.43
black parallelpiped
90(2)
C40H57CoN8O2S2
804.99
red plate
130(2)
monoclinic
triclinic
triclinic
(
(
Space group
Unit cell dimensions
P21/c
P1
P1
,
a (A)
13.4541(5)
27.2013(11)
14.9702(6)
90
111.3830(10)
90
5101.5(3)
4
1.383
12.1152(4)
13.5131(5)
14.1852(5)
84.9540(10)
79.8880(10)
71.4810(10)
2166.57(13)
2
11.141(3)
12.666(4)
15.098(5)
106.96(2)
94.16(2)
98.56(2)
1999.9(11)
2
,
b (A)
,
c (A)
h (°)
i (°)
k (°)
V (A3)
Z
Dcalc (g cm−3
)
1.549
1.337
Absorption coefficient (v) 0.555
1.016
0.579
(mm−1
)
Goodness-of-fit on F2 a
1.143
5.36
12.00
1.050
3.86
8.53
1.010
4.07
9.72
b
R1 (%)
c
Rw2 (%)
a Goodnss-of-fit=[ꢀ[w(Fo2−Fc2)2]/M−N)]1/2 (M=number of reflections, N=number of parameters refined).
b R1=ꢀꢁꢁFoꢁ−ꢁFcꢁꢁ/ꢀꢁFoꢁ.
c Rw2=[ꢀ[w(Fo2−Fc2)2]/ꢀ[w(Fo2)2]]1/2
.
thioether moieties are not involved in coordination. All
attempts to isolate a Co(III) complex with bound
thioether group(s) with PyPSMe2− have so far been
unsuccessful. This is somewhat surprising since many
Co(III) complexes with bound thioether (SR) groups
have been synthesized directly from cobalt salts and
ligands containing SR groups [17–20].
Both the availability of the monomeric model com-
plex (Et4N)2[Co(PyPS)(CN)] in this research group and
the reports on conversion of thiolato complexes to
thioether species by the use of alkyl halides [12,13,21]
prompted us to try to prepare (Et4N)2[Co(PyPSMe)-
(CN)] via the reaction of (Et4N)2[Co(PyPS)(CN)] with
iodomethane. All attempts in this direction resulted in
orange solutions from which only insoluble and in-
tractable orange residues have been obtained. As the
last option, we subjected the dimeric complex
(Et4N)2[Co2(PyPS)2] to react with iodomethane in ace-
tonitrile.
lates are converted into thioether groups. The higher
basicity of the terminal thiolato sulfurs compared to
that of the bridging ones is clearly responsible for this
selected methylation leading to 2. Such behavior has
been observed in thiolato-bridged nickel complexes
[22,23]. The conversion of the thiolato sulfurs to
thioether moieties results in a loss of charge and the
neutral complex 2 precipitates out of the reaction mix-
ture. This allows for isolation of 2 as a pure compound
and in high yield.
Since our original intention was to synthesize a
monomeric Co(III) complex with bound thioethers, we
decided to split the thiolato bridge of 2 with the aid of
CN−. Such reaction had yielded (Et4N)2[Co(PyPS)-
(CN)] from (Et4N)2[Co2(PyPS)2] before. Reaction of
CN− does split the thiolato bridge in 2. However, only
complex 3 can be isolated from a reaction mixture
containing 2 and 2 equiv. of (Et4N)CN. In this reaction,
approximately half of the starting dimer 2 is converted
into 3 while the remaining half stays unreacted. When
one uses 4 equiv. of (Et4N)CN in this reaction, complex
3 is isolated as the only product and in high yield. Since
reaction of CN− with 2 in MeCN in the presence of air
slowly oxidizes the thiolato sulfur to S-bound sulfenate
(SꢁO) group, anaerobic conditions are required for
isolation of complex 3 in pure form. Collectively, all
these results indicate that in no case one obtains a
monomeric Co(III) complex with carboxamido nitro-
gens and bound thioether group. This in turn suggests
that a thioether group is not a good donor for Co(III)
This reaction afforded a new dimeric species namely,
[Co2(PyPS(SMe))2] (2) in which only the terminal thio-

L.A. Tyler et al. / Inorganica Chimica Acta 321 (2001) 135–141
139
Table 2
support for this notion comes from the fact that reac-
tion of 2 with ligands like N-methylimidazole (N-
MeIm) or pyridine (py) affords a dimeric species (still
thiolato bridged) in which the thioether groups are
replaced by N-MeIm or py. These dimeric species have
been identified by NMR spectroscopy.
,
Selected bond distances (A) and bond angles (°)
(Et4N)[Co(PyPSMe)2]·acetone
Bond distances
Co(1)ꢀN(5)
Co(1)ꢀN(2)
Co(1)ꢀN(6)
Co(1)ꢀO(3)
Co(1)ꢀN(1)
Co(1)ꢀN(3)
S(1)ꢀC(2)
1.8408(16) N(1)ꢀC(7)
1.8529(16) S(3)ꢀC(23)
1.9508(19) O(3)ꢀC(29)
1.958(14) O(4)ꢀC(35)
1.9608(17) N(4)ꢀC(29)
1.9617(17) N(4)ꢀC(28)
1.770(3)
1.781(3)
1.809(2)
1.431(3)
1.763(2)
1.305(2)
1.235(3)
1.306(3)
1.407(3)
1.354(3)
1.457(4)
1.804(5)
1.796(6)
3.1. Structure of complexes
3.1.1. Structure of (Et4N)2[Co(PyPSMe)2]·acetone
(1·acetone)
N(6)ꢀC(35)
N(6)ꢀC(36)
S(4A)ꢀC(42A)
S(1)ꢀC(1)
S(2)ꢀC(21)
O(1)ꢀC(8)
O(2)ꢀC(14)
The asymmetric structure of the bis complex [Co(Py-
PSMe)2]2− is shown in Fig. 1. The coordination geome-
try around cobalt is pseudo-octahedral with distortions
arising from the bite angle of the 2,6-pyridinedicarbox-
amide units. Interestingly, this complex contains both
N-bound and O-bound carboxamido group pre-
sumably to relieve steric crowding between the pendant
aryl thioether groups and the ligand backbone. In 1, the
CoꢀNpep bond and average CoꢀNpy distances are
1.235(3)t S(4B)ꢀC(42B)
1.241(2)
Bond angles
N(5)ꢀCo(1)ꢀN(2)
N(5)ꢀCo(1)ꢀN(6)
N(2)ꢀCo(1)ꢀN(6)
N(5)ꢀCo(1)ꢀO(3)
N(2)ꢀCo(1)ꢀO(3)
N(6)ꢀCo(1)ꢀO(3)
O(3)ꢀCo(1)ꢀN(3)
N(1)ꢀCo(1)ꢀN(3)
177.98(7) C(2)ꢀS(1)ꢀC(1)
83.03(8) C(20)ꢀS(2)ꢀC(21)
97.17(7) C(14)ꢀN(3)ꢀC(15)
82.74(7) C(23)ꢀS(3)ꢀC(22)
97.08(6) O(3)ꢀC(29)ꢀN(4)
165.74(7) O(3)ꢀC(29)ꢀC(30)
102.72(13)
101.09(11)
120.33(17)
102.20(12)
129.23(18)
113.43(17)
88.97(7) C(41A)ꢀS(4A)ꢀC(42A) 102.2(2)
164.11(7) C(41B)ꢀS(4B)ꢀC(42B) 103.7(2)
,
1.9578(19) and 1.8469(16) A, respectively. The CoꢀOpep
,
bond length is 1.958(14) A. These values are well within
[Co2(PyPS(SMe))2]·1.5acetone·0.5MeCN
Bond distances
the range of such distances in Co(III) complexes con-
taining bound carboxamido-N and pyridine-N donors
[24].
Co(1)ꢀN(2)
Co(1)ꢀN(3)
Co(1)ꢀN(1)
Co(1)ꢀS(2)
Co(1)ꢀS(3)
Co(1)ꢀS(1)
Co(2)ꢀS(3)
1.8516(17) Co(2)ꢀS(2)
1.9181(16) Co(2)ꢀS(4)
1.9401(16) S(1)ꢀC(1)
2.2229(6) S(1)ꢀC(39)
2.2640(6) O(1)ꢀC(7)
2.2828(6) N(3)ꢀC(13)
2.2270(5) N(3)ꢀC(14)
2.2797(6)
2.2821(5)
1.787(2)
1.805(2)
1.235(2)
1.360(3)
1.403(3)
3.1.2. Structure of [Co2(PyPS(SMe))2]·1.5
acetone·0.5MeCN (2·1.5 acetone·0.5MeCN)
The dimeric structure of complex 2, shown in Fig. 2,
is very similar to the structure of (Et4N)2[Co2(PyPS)2]
reported by this group previously [11]. Methylation of
(Et4N)2[Co2(PyPS)2] results in (Et4N)2[Co2(PyPS-
Bond angles
N(2)ꢀCo(1)ꢀN(3)
N(2)ꢀCo(1)ꢀN(1)
N(3)ꢀCo(1)ꢀN(1)
N(2)ꢀCo(1)ꢀS(2)
N(3)ꢀCo(1)ꢀS(2)
N(2)ꢀCo(1)ꢀS(3)
N(3)ꢀCo(1)ꢀS(3)
83.18(7) S(2)ꢀCo(1)ꢀS(3)
82.43(7) S(2)ꢀCo(1)ꢀS(1)
164.62(7) N(4)ꢀCo(2)ꢀN(6)
169.01(5) N(4)ꢀCo(1)ꢀS(2)
89.06(5) S(3)ꢀCo(2)ꢀS(2)
88.97(5) S(3)ꢀCo(2)ꢀS(4)
96.69(5) C(39)ꢀS(1)ꢀCo(1)
84.20(2)
86.16(2)
163.77(7)
170.31(4)
83.74(2)
83.16(2)
107.86(8)
(SMe))2]
in
which
the
pentadentate
ligand
PyPS(SMe)2− occupies five coordination positions
around each Co(III) center. The thiolato S donor of
each ligand bridges the two cobalt centers and com-
pletes the pseudo-octahedral geometry around the
metal sites. In 2, the average CoꢀSbridging bond distance
(Et4N)2[Co(PyPS(SMe))(CN)2]·MeCN
Bond distances
,
is 2.2622(6) A which is identical to the average
Co(1)ꢀN(2)
Co(1)ꢀC(21)
Co(1)ꢀC(22)
Co(1)ꢀN(3)
Co(1)ꢀN(1)
Co(1)ꢀS(2)
1.859(2)
1.912(3)
1.925(2)
1.926(3)
1.973(2)
S(1)ꢀC(1)
S(1)ꢀC(2)
O(1)ꢀC(8)
N(1)ꢀC(8)
N(4)ꢀC(22)
1.800(3)
1.775(3)
1.238(3)
1.344(3)
1.149(3)
1.144(4)
CoꢀSbridging bond distance for (Et4N)2[Co2(PyPS)2]
,
(2.2623(15) A). The average CoꢀSMe bond distance is
,
2.2825(1) A which is within the range of previously
reported Co(III)ꢀthioether bond lengths [21,25,26]. The
remaining metric parameters of 2 (Table 2) are similar
to that of (Et4N)2[Co2(PyPS)2] and other Co(III) com-
plexes with bound pyridine and carboxamido nitrogens
[24,27].
2.2555(10) N(5)ꢀC(21)
Bond angles
N(2)ꢀCo(1)ꢀC(21)
N(2)ꢀCo(1)ꢀC(22)
92.24(10) N(2)ꢀCo(1)ꢀS(2)
89.14(9) C(21)ꢀCo(1)ꢀS(2)
171.10(6)
89.99(8)
88.71(7)
88.65(7)
107.48(6)
100.07(14)
176.8(3)
177.7(2)
C(21)ꢀCo(1)ꢀC(22) 178.57(11) C(22)ꢀCo(1)ꢀS(2)
N(2)ꢀCo(1)ꢀN(3)
C(21)ꢀCo(1)ꢀN(3)
C(22)ꢀCo(1)ꢀN(3)
N(2)ꢀCo(1)ꢀN(1)
C(22)ꢀCo(1)ꢀN(1)
N(3)ꢀCo(1)ꢀN(1)
82.76(9) N(3)ꢀCo(1)ꢀS(2)
89.20(10) N(1)ꢀCo(1)ꢀS(2)
91.33(9) C(2)ꢀS(1)ꢀC(1)
81.16(8) N(5)ꢀC(21)ꢀCo(1)
90.06(9) N(4)ꢀC(22)ꢀCo(1)
163.84(8)
3.1.3. Structure of
(NEt4)2[Co(PyPS(SMe))(CN)2]·MeCN (3·MeCN)
The structure of the anion of 3 is shown in Fig. 3.
The two cyanide ligands are trans to each other with an
,
average CoꢀC bond length of 1.9188(3) A. The CoꢀNpy
and average CoꢀNpep bond distances of 3 (1.859(2) and
,
1.9497(3) A, respectively) are very similar to the corre-
centers when hard ligands such as carboxamido nitro-
gens are present in the coordination sphere. Further
sponding distances noted in 1, 2, and other related
complexes [24,27–29].

140
L.A. Tyler et al. / Inorganica Chimica Acta 321 (2001) 135–141
The Co(III)ꢀSR bonds in known thioether complexes
are quite stable and resistant to ligand substitution
[13,17,26]. In contrast, the bound thioether groups in 2
are replaced easily by ligands like py and N-MeIm.
These ligand substitution reactions can be monitored
1
by H NMR spectroscopy. Thus addition of 5 equiv. of
N-MeIm to a solution of 2 in DMSO results in deliga-
tion of the SMe group (1.19 ppm peak of bound SMe
shifts to 1.89 ppm) and binding of N-MeIm at that site.
The resulting complex, however, remains dimeric (thio-
lato bridge intact) as indicated by other peaks of the
ligands including the characteristic one at ꢀ5.4 ppm.
The thiolato-bridge of 2 is split only when one uses
CN− as the incoming ligand. Reaction of 2 with CN−
affords the monomeric dicyano complex (Et4N)2-
[Co(PyPS(SMe))(CN)2] (3) with pendant thioether
group (SMe peak at 2.24 ppm) within 2 h at room
temperature. Since analogous reaction of CN− with
(Et4N)2[Co2(PyPS)2] does not bring about scission of
any Co(III)ꢀS bond even after 24 h, it is evident that
CoꢀSR bonds are considerably weakened when addi-
tional carboxamido groups are present in the coordina-
tion sphere.
Fig. 2. Thermal ellipsoid plot (50% probability level) of 2 showing the
numbering scheme. Hydrogen atoms are omitted for the sake of
clarity.
The position of the SMe peak in the 1H NMR
spectra of the present complexes provides helpful in-
sight regarding their structures. This peak appears at
2.43 ppm in the spectrum of free PyPSMeH2 in DMSO-
d6 and shifts upfield when ligated to Co(III) (1.19 ppm
in 2). In complex 3, the pendant SMe group exhibits a
resonance at 2.24 ppm which is similar to that noted for
the free ligand. In the case of complex 1, the unbound
thioether groups are inequivalent and exhibit three
resonances at 1.59 (3H) and 1.54 (3H) and 2.06 ppm
(6H) in DMSO-d6. Close examination of the crystal
structure (Fig. 1) reveals that two of the four SMe
groups have significant interaction with the p-cloud of
the phenyl rings on the ligand frames. We assign the
peaks at 1.59 and 1.54 ppm to these two SMe groups.
The remaining two pendant SMe groups have little
interaction with the ligand backbone and hence are
assigned to the resonance at 2.06 ppm (similar to the
SMe group of free PyPSMeH2).
Although (Et4N)2[Co(PyPS)(CN)] promotes signifi-
cant hydrolysis of acetonitrile in aqueous buffer (pH
9.5) at 50 °C [11], complex 3 shows no such activity
under similar conditions. Indeed, none of the present
complexes initiate any hydrolysis of nitriles. This find-
ing indicates that presence of thiolato sulfur(s) could be
a requirement for the model complexes to promote
hydrolysis of nitriles.
Fig. 3. Thermal ellipsoid plot (50% probability level) of the anion of
3 showing the numbering scheme. Hydrogen atoms are omitted for
the sake of clarity.
3.2. Properties
The conversion of bound thiolate to thioether group
in Co(III) complexes is reported to impart little change
on the electronic configuration and hence Co(III) com-
plexes containing bound thioether moieties exhibit in-
tense ligand-to-metal charge transfer (LMCT) bands
much like the corresponding thiolato complexes. For
example, Deutsch and coworkers found that conversion
of the bound thiolato sulfurs of [(en)2Co(SCH2-
CH2NH2)]2+ to methyl-thioether (SMe) group results
in a 2-nm blue shift in the LMCT band [26]. Likewise,
complex 2 exhibits a strong LMCT band at 430 nm in
acetonitrile which is very similar to the LMCT band of
(Et4N)2[Co2(PyPS)2] (427 nm in acetonitrile). The thio-
late/thioether species 2 also displays a comparatively
weak absorption at 570 nm.
4. Conclusions
Although several Co(III) complexes with coordinated
thioether (SR) groups have been reported, the results of

L.A. Tyler et al. / Inorganica Chimica Acta 321 (2001) 135–141
141
[4] M. Kobayashi, T. Nagasawa, H. Yamada, TIBTECH 10 (1992)
402.
[5] T. Nagasawa, H. Yamada, Trends Biotechnol. 7 (1989) 153.
[6] W. Huang, J. Jia, J. Cummings, M. Nelson, G. Schneitder, Y.
Lindqvist, Structure 5 (1997) 691.
[7] S. Nagashima, M. Nakasako, N. Dohmae, M. Tsujimura, K.
Takio, M. Odaka, M. Yohda, N. Kamiya, I. Endo, Nat. Struct.
Biol. 5 (1998) 347.
[8] T. Murakami, M. Nojiri, H. Nakayama, M. Odaka, M. Yohda,
N. Dohmae, K. Takio, T. Nagamune, I. Endo, Protein Sci. 9
(2000) 1024.
the present work now indicates that the thioether (SR)
group is not a good ligand for Co(III) when carboxa-
mido nitrogens are present. The only complex with
carboxamido-N and thioether-S donors that we have
been able to isolate is 2. The CoꢀS(R) bond in this
complex is, however, weak and is substituted readily by
other ligands. Collectively, the results suggest that
simultaneous coordination of carboxamide group and
methionine residues to Co(III) center in metalloen-
zymes is unlikely. The choice of cysteine (instead of
methionine) sulfurs as donors for the Co(III) site in
nitrile hydratase could be related to this finding.
[9] B.A. Brennan, G. Alms, M.J. Nelson, L.T. Durney, R.C. Scar-
row, J. Am. Chem. Soc. 118 (1996) 9194.
[10] T. Nagasawa, K. Takeuchi, H. Yamada, Eur. J. Biochem. 196
(1991) 581.
[11] J.C. Noveron, M.M. Olmstead, P.K. Mascharak, J. Am. Chem.
Soc. 121 (1999) 3553.
[12] M.J. Root, E. Deutsch, Inorg. Chem. 20 (1981) 4376.
[13] R.H. Lane, F.A. Sedor, M.J. Gilroy, P.F. Eisenhardt, J.P.
Bennett, R.X. Ewall, L.E. Bennett, Inorg. Chem. 16 (1977) 93.
[14] G.C. Schlessinger, Inorg. Synth. 9 (1967) 160.
[15] J.C. Noveron, M.M. Olmstead, P.K. Mascharak, J. Am. Chem.
Soc. 123 (2001) 3247.
[16] S. Parkin, B. Moezzi, H.J. Hope, Appl. Crystallogr. 28 (1995)
53.
[17] W.G. Jackson, A.M. Sargeson, Inorg. Chem. 17 (1978) 2165.
[18] T. Isago, K. Igi, J. Hidaka, Bull. Chem. Soc. Jpn. 2 (1979) 407.
[19] K. Okamoto, K. Wakayama, H. Einaga, S. Yamada, J. Hidaka,
Bull. Chem. Soc. Jpn. 56 (1983) 165.
5. Supplementary material
Crystallographic data for the structural analysis have
been deposited with the Cambridge Crystallographic
Data Centre, CCDC Nos. 167308–167310 for com-
plexes 1–3 respectively. Copies of this information may
be obtained free of charge from The Director, CCDC,
12 Union Road, Cambridge, CB2 1EZ, UK (fax: +44-
1223-336-033; e-mail: deposit@ccdc.cam.ac.uk or www:
http://www.ccdc.cam.ac.uk).
[20] V.M. Kothari, D.H. Busch, Inorg. Chem. 8 (1969) 2276.
[21] L. Roecker, M.H. Dickman, D.L. Nosco, R.J. Doedens, E.
Deutsch, Inorg. Chem. 22 (1983) 2022.
Acknowledgements
[22] D.H. Busch, D.C. Jicha, M.C. Thompson, J.W. Wrathall, E.
Blinn, Adv. Chem. Ser. 37 (1963) 125.
[23] S.G. Murray, F.R. Hartley, Chem. Rev. 81 (1981) 365 (and
references therein).
[24] F.A. Chavez, J.M. Rowland, M.M. Olmstead, P.K. Mascharak,
J. Am. Chem. Soc. 114 (1992) 3841.
[25] G.J. Gainsford, W.G. Jackson, A.M. Sargeson, J. Chem. Soc.,
Chem. Commun. (1979) 802.
This research was supported by a grant from the
National Institute of Health (GM61636). L.T. was a
recipient of a GAANN fellowship from the US Depart-
ment of Education.
[26] R.C. Elder, G.J. Kennard, M.D. Payne, E. Deutsch, Inorg.
Chem. 5 (1978) 1296.
[27] F.A. Chavez, M.M. Olmstead, P.K. Mascharak, Inorg. Chem.
36 (1997) 6323.
References
[1] M. Kobayashi, S. Shimizu, Eur. J. Biochem. 261 (1999) 1.
[2] M. Kobayashi, S. Shimizu, Nat. Biotechnol. 16 (1998) 733.
[3] H. Yamada, M. Kobayashi, Biosci. Biotechnol. Biochem. 60
(1996) 1391.
[28] L.A Tyler, J.C. Noveron, M.M. Olmstead, P.K. Mascharak,
Inorg. Chem. 39 (2000) 357.
[29] L.A Tyler, J.C. Noveron, M.M. Olmstead, P.K. Mascharak,
Inorg. Chem. 38 (1999) 616.
.