Valence-Tautomerism-Driven Aromatic Nucleophilic Substitution in Cobalt-Bound Tetrabromocatecholate Ligands – Influence of Positive Charge at the Ligand Backbone on Phenoxazinone Synthase Activity

Article abstract of DOI:10.1002/ejic.201701176

The mononuclear Co^III complex [Co(Br₃Cat-py)₂(py)₂]Cl·8H₂O (1, py = pyridine, Br₃pyCatH₂ = 3,5,6-tribromo-4-pyridiniumcatechol) was synthesized through the reaction of CoCl₂·6H₂O with tetrabromocatechol in the presence of an excess of pyridine at elevated temperature. The solid-state structure was determined by X-ray crystallography, which disclosed the valence-tautomerism-induced aromatic nucleophilic substitution of the tetrabromocatecholate ligands by pyridine. A cyclic voltammetry study revealed the redox flexibility of both the transition-metal centre and the coordinated redox-active ligand in this complex. Moreover, 1 exhibits moderately strong catalytic activity and mimics the function of phenoxazinone synthase. A detailed kinetic study disclosed that the extra positive charges at the ligand backbone resulting from the substitution of the Br atoms by pyridyl groups could play an anchoring role for the stabilization of the complex–substrate intermediate. This process resembles those in biological systems, in which the extraordinary catalytic activities of metalloenzymes in various biochemical processes are associated with substrate recognition and the stabilization of the reactive intermediates through diverse supramolecular forces. DFT calculations at the M06-2X/6-31+G* level of theory were used to support the mechanistic aspects related to both the redox-driven aromatic nucleophilic substitution and the biomimetic catalysis.

Full text of DOI:10.1002/ejic.201701176

A Journal of
Accepted Article
Title: Valence tautomerism driven IPSO substitution in cobalt-bound
tetrabromocatecholate ligands: Influence of positive charge at
ligand backbone on phenoxazinone synthase activity
Authors: Anangamohan Panja and Antonio Frontera
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10.1002/ejic.201701176
European Journal of Inorganic Chemistry
FULL PAPER
Valence tautomerism driven aromatic nucleophilic substitution in cobalt-
bound tetrabromocatecholate ligands: Influence of positive charge at
ligand backbone on phenoxazinone synthase activity
Anangamohan Panja,*[a] and Antonio Frontera[b]
Abstract:
A
mononuclear Co(III) complex, [Co(Br3Cat-
redox shuttling between the oxidation state of the coordinated
redox-active ligands [10]. Cobalt complexes with these ligands
have recently been explored as catalysts for C–C coupling
reactions [9,10]. Furthermore, Mn(III) complexes with electron
deficient catechols such as tetracholorocatechol were reported
to be good candidates for the catalytic production of hydrogen
peroxide from molecular oxygen under ambient condition in the
presence of hydroxylamine or hydrazine as a reducing agent
[11,12]. Recently, we observed the valence tautomeric transition
induced aromatic nucleophilic substitution of a Br atom by
pyridine from a coordinated tetrabromocatecholate ligand [13]. We
have also observed thermally induced valence tautomeric
transition in cobalt-tetrabromocatecholate system in the solid
state [14]. Therefore, we anticipated that, like manganese system,
similar valence tautomeric transition driven aromatic nucleophilic
substitution may be possible in cobalt complexes in the solution
state. It is worth mentioning that the synthesis of bromo-
derivatives of pyrocatechols is driven by a part of their important
biological activities as these bromopyrocatechols may exhibit
enzyme inhibition, cytotoxicity, feeding deterrent and microbial
py)2(py)2]Cl∙8H2O (1), where py is pyridine and Br3pyCatH2 is
3,5,6-tribromo-4-pyridiniumcatechol, has been synthesized by
the reaction of CoCl2·6H2O with tetrabromocatechol in the
presence of excess pyridine at elevated temperature. The solid
state
crystallographycally that discloses the valence tautomerism
induced aromatic nucleophilic substitution of
structure
has
been
determined
by
X-ray
a
tetrabromocatecholate ligand by pyridine. Cyclic voltammetry
study reveals the redox flexibility of both the transition metal and
the coordinated redox active ligand in this complex. Moreover,
the present complex exhibits moderately strong catalytic activity
mimicking the function of phenoxazinone synthase. Detailed
kinetic study further discloses that the extra positive charges at
the ligand backbone, resulting from the substitution of Br atoms
by pyridines, could play anchoring role for stabilization of the
complex-substrate intermediate, which has resemblance with the
biological systems where extraordinary catalytic activity of the
metalloenzymes in various biochemical processes is associated
with the substrate recognition and stability of the reactive
intermediates through diverse supramolecular forces. DFT
calculations at the M06-2X/6-31+G* level of theory are used to
support the mechanistic aspects related to both redox-driven
aromatic nucleophilic substitution and biomimetic catalysis.
activities [15–17]. Protein tyrosine phosphatase inhibitory activity of
[18]
some bromopyrocatechols has also been examined
.
Therefore, one of the ways to derive halogen-substituted
catechols is the metal promoted aromatic nucleophilic
substitution of halides in which drifting of electron density from
aromatic ring to metal centre welcome substitution at aromatic
ring [19]. Recently, we have explored that Mn(III) complexes with
tetrahalocatecholate ligands could exhibit biomimetic catalysis
mimicking the function of phenoxazinone synthase and catechol
oxidase [13,20]. The former is a multicopper metalloenzyme that
catalyses the oxidative coupling of substituted o-aminophenols
to phenoxazinone chromophores in the final step for the
biosynthesis of actinomycin D [21–23]. We further envisioned that
cobalt complexes derived from tetrabromocatecholate ligand
may exhibit similar activities. Accordingly, as a part of our
Introduction
Transition metal complexes with redox-active organic
ligands, commonly known as valence tautomer, may exist in
different electronic states depending upon the oxidation states of
both transition metal and redox-active ligand. Such valence
tautomeric compounds that can be switched between two or
more electronic states, under the influence of external stimuli
such as heat and light, are of great significance for future
applications in data storage, display devices, and molecular
spinotronics [1–7]. These compounds have also much importance
in the field of biomimetic catalysis, C–H bond activation, C–C
cross coupling, etc [8–10]. Soper et al. have reported that the
nucleophilic and electrophilic behaviours of square planar Co(III)
complexes can be mediated by the facile reversible ligand-based
ongoing program on the transition metal-dioxolene chemistry
[13,14,24–26]
and biomimetic catalysis
, herein the synthesis,
structure and phenoxazinone synthase like activity of
a
mononuclear [Co(Br3Cat-py)2(py)2]Cl∙8H2O (1), where py is
pyridine and Br3pyCatH2 is 3,5,6-tribromo-4-pyridiniumcatechol,
are reported. Theoretical study has also been performed to
support the experimental facts especially to explore the
mechanistic aspects associated in the chemical reactivity.
[a]
[b]
Dr. A. Panja
Postgraduate Department of Chemistry, Panskura Banamali
College, Panskura RS, WB 721152, India
E-mail: ampanja@yahoo.co.in
Results and Discussion
Prof. A Frontera
Syntheses and general characterizations
Departament de Química, Universitat de les Illes Balears, Crta. de
Valldemossa km 7.5, 07122 Palma de Mallorca (Baleares), Spain
Reaction of a mixture of cobalt(II) chloride hexahydrate and
tetrabromocatechol (Br4CatH2) in the presence of excess
pyridine in methanol/acetone (1:1, v/v) mixed solvent in heating
condition resulted a dark-brown solution from which a brown
Supporting information for this article is given via a link at the end of
the document. ((Please delete this text if not appropriate))
1
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10.1002/ejic.201701176
European Journal of Inorganic Chemistry
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crystalline material of [Co(Br3Cat-py)2(py)2]Cl∙8H2O (1) was
isolated in ca. 38% yield. Interestingly, this reaction involves
nucleophilic aromatic substitution of a para Br atom related to
OH groups of the coordinated tetrabromocatecholate ligands by
pyridine. Recently, we have reported similar reaction where
substitution of a para Br atom related to OH groups of one of the
coordinated tetrabromocatecholate ligands by pyridine was
observed [13]. Remarkably, in the present system, both the
coordinated tetrabromocatecholate ligands are susceptible to
nucleophilic substitution reaction. A combined experimental and
theoretical studies revealed that the valence tautomeric
conversion from Mn(III)-tetrabromocatecholate to Mn(II)-
tetrabromosemiquinonate favours the aromatic nucleophilic
substitution in the aromatic ring. Theoretical study further
showed that the LUMO is located on delocalized
tetrabromosemiquinonate and tetrabromocatecholate ligands
and the largest atomic coefficients that participate in this
molecular orbital are located at the carbon atoms that suffer the
nucleophilic attack of pyridine [13]. These studies supported the
fact that at higher temperature the valence tautomeric
conversion from Mn(III)-tetrabromocatecholate to Mn(II)-
tetrabromosemiquinonate increases the electrophilic character of
aromatic carbon atom at para position with respect to OH group
of the semiquinonate ligand, thereby favouring the aromatic
nucleophilic substitution of Br by pyridine. In our recent report,
we examined the valence tautomeric behaviour in Co(III)-
tetrabromocatecholate system and found that compound trans-
[pyH][Co(Br4Cat)2(py)2]·2H2O·2C3H6O (A) is susceptible to
in Fig. 2a, the substitution is energetically favourable by 20.02
kcal/mol in solution, thus explaining the formation of compound 1
if excess of pyridine is present in the synthesis of A.
This complex is air-stable and moisture insensitive, and is
soluble in common organic solvents like methanol, acetonitrile
and DMF. The purity of the bulk sample was verified by
elemental analysis. Molar conductance of 1 in methanol is found to
be 96 Ω−1 cm2 mol−1 that suggests complex 1 is a 1:1 electrolytic type
compound. Moreover, a peak at m/z = 1062.4 in the mass spectrum
of 1 in methanol is agreed well with the complex cation of formula
[Co(Br3Cat-py)2(py)2]+ (calculated m/z = 1062.6 ). These solution
studies strongly support retention of the structure of the complex
cation in the solution state.
IR spectroscopic data could be helpful for distinguishing
the variable oxidation states of redox-active dioxolene ligand in
the metal complexes. Such ligands in the semiquinonate state
generally exhibit characteristic C–O stretching band in the region
1430–1480 cm–1, while it is found below1430 cm–1 for the fully
reduced catecholate state of the ligand [27,28]. In the IR spectrum
of 1, a strong and sharp band found at 1431 cm–1, which can be
assigned to the catecholate C–O stretching of 3,5,6-tribromo-4-
pyridiniumcatecholate ligand (Fig. S1). The catecholate state of
the ligand in 1 is further supported by the presence of medium
intense band at 1273 cm–1. Moreover, another strong bifurcated
bands observed at 1619 and 1637 cm–1 for 1 can be assigned to
pyridyl C–N stretching. The bifurcation of the band is indicative
of the presence of two different kinds of pyridine moieties in the
complex,
consistent
with
the
X-ray
crystallographic
valance
tautomeric
conversion
from
Co(III)-
characterization in the solid state. Furthermore, a broad band at
3427 cm–1 in the IR spectrum is typical for O–H stretching
vibration of the lattice water molecules.
tetrabromocatecholate to Co(II)-tetrabromosemiquinonate at the
elevated temperature
[14]
.
Such entropy driven valence
tautomeric conversion is much favourable in the gaseous or
liquid phase. Therefore, the mechanism of formation of the
present compound can be explained by the valence tautomeric
conversion of compound A to its tautomeric form 1a as shown in
scheme 1. This intramolecular ligand-to-metal electron transfer
facilitates the aromatic nucleophilic substitution of only the
bromide at para position with respect to semiquinonato oxygen
atom by pyridine at elevated temperature. The pyridine for Br-
substitution in the tetrabromosemiquinonate ring in 1a, followed
by the reversal of electron transfer (metal-to-ligand) produces an
unsymmetrical compound 1b. The repetition of same process for
other tetrabromocatecholate ligand leads to the formation of final
compound 1 (see scheme 1).
We have used DFT calculations to support the explanation
given above. In Fig. 1 we show the optimized complex A and its
valence tautomer 1a. We have represented the LUMO of A in
Fig 1a and it can be observed that it is located in the coordinated
pyridines. Consequently, the nucleophilic substitution at the
tetrabromocatechol ring is not possible in this tautomeric form
since the LUMO is not located in this ring. However, in the other
tautomeric form (1a) the LUMO is located in the
tetrabromocatechol ring, thus supporting the mechanistic
proposal given in Scheme 1. Moreover, the spin density plot
reveals that the spin is basically located at the Co(II) metal
centre with some delocalization to the atoms directly bonded to it.
There is also spin density equally distributed in both
tetrabromocatechol ligands.
Description
py)2(py)2]Cl∙8H2O (1)
of
crystal
structure
of
[Co(Br3Cat-
The crystal structure of 1 is depicted in Fig. 3 in which
complex cation, [Co(Br3Cat-py)2(py)2], sits on an inversion centre,
and crystalizes with a disordered chloride ion in two positions
and eight lattice water molecules. Selected geometrical
parameters of complex 1 is given in Table 1. The coordination
geometry around cobalt(III) centre is best described as a slightly
distorted octahedron in which the equatorial positions are
coordinated by two 3,5,6-tribromo-4-pyridiniumcatecholate
ligands and the remaining two axial positions of the octahedral
structure of the central Co atom are bonded with two pyridine
ligands. Although the trans angles are found to be ideal values
of 180° as dictated by the centre of symmetry, the slight
geometrical distortion is thereby associated with the marginal
deviation of bite angle (88.5(3) Å) of the dioxolene ligand from
ideal angle of 90°. Two aromatic rings in 3,5,6-tribromo-4-
pyridiniumcatecholate are mutually perpendicular to each other
as suggested by the dihedral angle between pyridyl and phenyl
rings of 86.98°, which is usual for such organic molecules
[11,13]
.
The Co–N(pyridine) and average Co–O (catecholate) bond
lengths in 1 are 1.948(8) and 1.885 (6) Å, respectively, and
which are comparable to that found in reported cobalt(III)-
catecholate complexes with similar coordination environments
[29–35]. The C–O and ring C–C (bearing catecholate –OH groups)
bond lengths of the coordinated o-dioxolene ligand provide
useful information regarding oxidation state of the coordinated
redox-active dioxolene ligand. The C–O bond distances are
In addition, we have also studied energetically the double
substitution of Br by pyridine in complex A. As can be observed
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10.1002/ejic.201701176
European Journal of Inorganic Chemistry
FULL PAPER
Scheme 1. Plausible mechanistic pathway for the synthesis of 1.
Fig. 1. LUMO plots of A (a) and 1a (b) and spin density of 1a (c)
at the M062x/6-31+G* level of theory.
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10.1002/ejic.201701176
European Journal of Inorganic Chemistry
FULL PAPER
Fig. 2. Reaction energies for the nucleophilic substitution of Br
by pyridine in complex A (a) and the ligand substitution of
pyridine by o-aminophenol in complex 1 (b).
Table 1. Selected bond lengths (Å) and bond angles (º) for
complex 1#
Co1–O1
Co1–O2
Co1–N2
1.884(6)
1.887(7)
1.948(8)
C1–O1
C1–O2
C1–C2
1.348(12)
1.359(11)
1.395(15)
O1–Co1–O2
O1–Co1–
O1a
88.5(3)
180.0
O2–Co1–N2
O1–Co1–N2
90.2(3)
89.8(3)
O2–Co1–
O2a
180.0
N2–Co1–N2a 180.0
# Symmetry code: a = 1–x, 1–y, 2–z
Fig. 3. Molecular structure of the complex cation of 1 showing
atom numbering scheme. Ellipsoids are drawn at 30%
probability level, and hydrogen atoms have been omitted for
clarity.
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10.1002/ejic.201701176
European Journal of Inorganic Chemistry
FULL PAPER
Fig. 4. Packing diagram of complex 1 viewed along the c axis
showing wavy water sheet.
molecules have been omitted. The 2D sheet is formed by
parallel arrangement of infinite 1D supramolecular chains
stabilized by Br···π interactions involving both coordinated
pyridine and 3,5,6-tribromo-4-pyridiniumcatecholate ligands.
Remarkably, each complex participates in two symmetrically
equivalent bifurcated Br···π interactions with distances of 3.59 to
the ring centroid of pyridine and 3.41 Å to the ring centroid of
catecholate ring.
usually shorter for semiquinonate state (ca. 1.28 Å) compared to
that found in the fully reduced catecholate state (ca. 1.34 Å) of
the ligands. Similarly, C–C bond distances of semiquinonate and
catecholate states of the ligands usually vary in the range 1.45–
1.48 Å and 1.36–1.44 Å, respectively [29–35]. In the present
complex, C–O and ring C–C bond distances are 1.353(11) Å
(average value) and 1.395(15) Å, respectively, indicating the
catecholate state of the dioxolene ligand. In order to further
support the Co(III)-catecholate charge distribution in 1 in the
solid state, we adopted the empirical method developed by
Brown to calculate the metrical oxidation state (MOS) of the
Electrochemical Study
Electrochemical studies of transition metal complexes with redox
active ligand could be useful to get insight into the electronic
structure of those complexes. The cyclic voltammogram of 1 in
methanol as depicted in Fig. 5 consists of two well-resolved
quasireversible oxidative responses with half-wave potentials
(E1/2) of 0.35 and 0.58 V versus ferrocene/ferrocenium couple,
and these closely associated oxidation processes of 1 are
attributable to the stepwise oxidation of two coordinated 3,5,6-
tribromo-4-pyridiniumcatecholate ligands to corresponding
semiquinonate forms [30,37]. In addition to the ligand based redox
processes, electrochemical study also reveals a metal based
redox event. Scanning the electrode potentials in the cathodic
direction, the cyclic voltammogram of 1 showed an irreversible
peak at –1.19 V, which is responsible for the reduction of
cobalt(III) to cobalt(II) centre. The irreversible nature of the
metal-based reduction process is probably due to the loss of
coordinated pyridine ligands during the electrochemical
reduction, which is associated with the increasing lability of
metal centre upon reduction, leading to significant modification
of the reduced species at the electrode surface.
redox active dioxolene ligand considering all C–O and ring C–C
[36]
bond distances
. The calculated MOS value of two
crystallographically equivalent dioxolene ligands in 1 is –2.03,
further suggesting the catecholate state of the dioxolene ligand
in the present system. The crystal packing of 1 as depicted in
Fig. 4 is quite interesting, in which water molecules form a wavy
sheet in the bc plane. Similar type of sheet is also constructed
by the complex cations in the same plane. These two different
kinds of parallel sheets propagate alternatingly along the
crystallographic a axis, leading to the 3D structure in the solid
state.
It is also worth noting that a network of Br···π interactions
is established in the solid state, as shown in Fig. S2. In this
representation (partial view) of the packing of 1 it can be
observed the formation of 2D sheets in the solid state
architecture. In this solid state representation, the Cl and water
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10.1002/ejic.201701176
European Journal of Inorganic Chemistry
FULL PAPER
complex 1 has been synthesized [14], as similar studies with
Mn(III)-catecholate systems revealed that the positive charge at
the ligand backbone brings the significantly enhanced catalytic
[13]
activity upon pyridyl substitution
. However, the time-
dependent spectral scanning in an identical reaction condition
shows that compound is almost inactive towards the
A
biomimetic catalytic activity related to the function of
phenoxazinone synthase (Fig. S3). Therefore, in the present
system, two extra positive charges of the substituted pyridinium
ions again play anchoring role for exhibiting significantly high
catalytic activity of complex 1. The present study is well
resemblance with the biological systems where the substrate
recognition and stabilization of reactive intermediates through
diverse supramolecular forces including hydrogen bonding and
– stacking interactions are considered the key factors behind
the extraordinary catalytic activity of the metalloenzymes in
various biochemical processes [46,47]. Therefore, the moderately
strong catalytic activity of 1 is likely due to the presence of two
pyridinium ions at ligand backbone which in turn stabilizes the
complex substrate intermediate as suggested by the rate
saturation kinetics. Thus, the catalytic cycle of the production of
2-aminophenoxazin-3-one is expected to start with the formation
of a complex-substrate intermediate, followed by the redox
decomposition of the intermediate at the rate determining step
with the production of o-aminophenol mono radical. This mono
radial by the reaction with o-aminophenol and molecular oxygen
yields the final product 2-aminophenoxazin-3-one through a
multiple step process as shown in Scheme 2.
Fig. 5. Cyclic voltammogram of
1
in methanol using
tetraethylammonium perchlorate as a supporting electrolyte at a
scan rate of 100 mV/s. Potentials were referenced to the Fc+/Fc
couple.
Phenoxazinone synthase like activity
Phenoxazinone synthase mimicking activity was examined by
UV-vis spectrophotometrically using o-aminophenol (OAP) as a
substrate [24–26,38–45]. First of all, it is important to check whether
the present complex is able to catalyse the oxidation of OAP in
aerobic condition. For this purpose, 2.0 × 10−5 M solution of the
complex was mixed with 1.0 × 10−2 M OAP in air-saturated
methanol, and the spectra were recorded at 5 min time intervals
at room temperature. The time-dependent spectral profile as
depicted in Fig. 6 reveals the progressive increase of the band
intensity at ca. 434 nm, characteristic of 2-aminophenoxazin-3-
one in methanol, suggesting the functional mimetic activity of the
present complex. Phenoxazinone synthase like activity of 1 is
further supported by the fact that the blank experiments using
cobalt(II) salt or pyridine or both of them did not show any
significant increase of the spectral band at 434 nm under
identical reaction condition. Detailed kinetic investigations are
further required to get insight into the catalytic efficiency of the
complex, and therefore, the kinetic studies at the maximum of 2-
aminophenoxazin-3-one band (434 nm) were performed for a
period of 10 min by mixing 2 × 10−5 M solutions of the complex
with variable concentration of the substrate maintaining pseudo-
first order condition. The initial reaction rate versus substrate
concentration plot shows a typical rate-saturation kinetics of
decreasing slope (Fig. 7), which is indicative of the formation of
a relatively stable complex-substrate intermediate prior to the
irreversible redox transformation of the intermediate in the rate
determining step. The Michaelis-Menten model and its double
reciprocal linear Lineweaver-Burk plot may be applied to analyse
these data (Fig. 7). Analysis of the experimental data yielded
We have used DFT calculations to study the first
mechanistic step proposed in Scheme
2 (see Fig. 2b).
Remarkably, the substitution of Py by OAP is energetically
favourable (–9.10 kcal/mol) giving support to the mechanism.
More interestingly, the presence of the pyridinium moiety in the
catechol ring contributes to the complexation of OAP to Co(III)
metal centre. That is, the coordinated OAP adopts
a
conformation where a C–H···π interaction is formed in addition
to the N–H···O hydrogen bond (see dashed lines in Fig. 2b). The
C–H···π interaction is remarkably short (2.34 Å) due to the
anionic nature of the coordinated OAP and the enhanced acidity
of the pyridinium aromatic H atoms.
Michaelis binding constant (KM) and Vmax values 6.08  10–3
M
)
and 1.70  10–7 M s–1, respectively. The turnover number (Kcat
value was calculated by dividing the Vmax by the concentration of
the catalyst used, and it is found to be 30.6 h–1.
Efficient biomimetic catalytic activity of complex 1 is
motivated us to examine the catalytic activity of trans-
[pyH][Co(Br4Cat)2(py)2]·2H2O·2C3H6O (A), through which
Fig. 6. Time course spectral profile showing progressive
formation of 2-aminophenoxazin-3-one at 434 nm by the
reaction of 0.01 M o-aminophenol with complex 1 (2 x 10–5 M) in
air-saturated methanol. Spectra were recorded 5 min time
intervals.
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10.1002/ejic.201701176
European Journal of Inorganic Chemistry
FULL PAPER
samples as KBr pellets were recorded in the range of 400–4000 cm–
1
on a PerkinElmer Spectrum Two Infrared spectrometer. Cyclic
voltammetric studies were performed in methanol at room
temperature using tetraethylammonium perchlorate as a supporting
electrolyte on a CH Instrument electrochemical workstation model
CHI630E using a platinum working electrode, a platinum wire
auxiliary electrode and a Ag/AgCl reference electrode. Electronic
absorption spectra were recorded using a PerkinElmer Lamda-35
spectrophotometer with a 1-cm path-length quartz cell.
Synthesis of [Co(Br3Cat-py)2(py)2]Cl∙8H2O (1)
CoCl2·6H2O (119 mg, 0.5 mmol) and Br4CatH2 (426 mg, 1.0 mmol)
were mixed in 20 mL of methanol/acetone (1:1, v/v) with stirring.
Then a solution of pyridine (790 mg, 10.0 mmol) in 10 mL of
methanol was added dropwise with continuous stirring, and the
resulting solution was allowed to heat at 50 ºC for about 1 h during
which time the colour of the solution changed to dark brown. The
reaction mixture was then filtered and left at ambient temperature for
slow evaporation. Crops of dark-brown block-crystals suitable for
structural studies separated out from the solution after several days.
These crystals were isolated via suction filtration, washed with
methanol/ether, and dried in air at room temperature. Yield: 0.236 g
(38 %). Anal Calcd. for C32H36Br6ClCoN4O12: C, 30.93; H, 2.92; N,
4.51. Found: C, 30.48; H, 3.09; N, 4.39. FTIR (KBr, cm–1): 3427 br,
1619 s, 1637 s, 1431 s, 1273 m.
Fig. 7. Initial rate versus substation concentration plot for the
oxidation of o-aminophenol catalysed by complex 1 in air-
saturated methanol at room temperature. Symbols and solid line
denote experimental and simulated profiles, respectively. Inset
showing the Lineweaver-Burk plot.
Conclusions
X-ray diffraction study
Single crystal X-ray diffraction data for 1 were collected on a Bruker
Kappa Apex-II CCD area-detector diffractometer (Mo-Kα graphite-
monochromated radiation, λ = 0.71073 Å) at 150(2) K. Several
images were collected by scanning in φ and ω directions and were
averaged during refinement cycles. Data processing was performed
using the Bruker SAINT software package, and all intensity data
were corrected by multi-scan absorption method implemented in
SADABS program [48]. The structures were solved by the direct
method and refined by a full-matrix least squares-based method on
F2 using the SHELXL program [49]. All non-hydrogen atoms were
refined with anisotropic thermal parameters, while hydrogen atoms
attached to carbon atoms were placed at geometrically idealized
positions with individual isotropic thermal parameters equal to 1.2
times of their parent atoms, but were not refined. Some of the
hydrogen atoms attached to the lattice water molecules were located
on the difference Fourier map, and they have been refined with a
riding model approximation where thermal parameters have been
fixed at 1.5 times of their respective parent atoms. Important
crystallographic data together with refinement details are given in
Table 2.
A
mononuclear Co(III)-catecholate complex (1) has been
synthesized by the reaction of cobalt(II) chloride in the presence
of pyridine in aerobic condition. The structural characterization of
1
reveals the valence tautomeric induced nucleophilic
substitution of Br atom at the para position of the
a
semiquinonato-O, thereby showing the possibility of the
synthesis of substituted bromopyrocatechols that have immense
importance in the biological field. Moreover, the present complex
is catalytically active towards the function of phenoxazinone
synthase. Detailed study further discloses that the extra positive
charges because of the substitution of Br atoms by pyridines
could play anchoring role for the stabilization of the complex-
substrate intermediate, which has resemblance with the
biological systems where substrate recognition and stability of
important reactive intermediates through diverse supramolecular
forces are considered the key factors behind the extraordinary
catalytic activity of the metalloenzymes in various biochemical
processes. Both the valence tautomerism and some key
mechanistic steps of the biomimetic catalysis have been
validated using DFT calculations including reaction energies and
spin density/orbital plots.
Kinetics of the oxidation of o-aminophenol
Catalytic oxidation of o-aminophenol (OAP) was examined by
mixing 100 equivalents of o-aminophenol with 2.0  10–5 M solution
of 1 in methanol under aerobic condition at room temperature.
Reaction kinetics was followed spectrophotometrically by monitoring
Experimental section
Materials and physical measurements
Tetrabromocatechol monohydrate, o-aminophenol (OAP), cobalt(II)
chloride hexahydrate and pyridine were purchased from commercial
sources and used as received. Some other chemicals and solvents
were of reagent or analytical grade and used without further
purification. Compound trans-[pyH][Co(Br4Cat)2(py)2]·2H2O·2C3H6O
(A) was synthesized following the procedure as described in our
recent paper [14].
the increase of the absorbance with time at 434 nm ( = = 24 × 103
[50]
M–1 cm–1)
, which is indicative of the formation of 2-
aminophenoxazin-3-one in methanol. To determine the various
kinetic parameters including turnover number, 2.0  10–5 M solutions
of the complex were mixed with at least 10 equivalents of substrate
to maintain pseudo-first order condition. Rate of the reaction was
determined by the initial rate method.
Elemental analyses for C, H, and N were conducted in a
PerkinElmer 240C elemental analyser. The infrared spectra of the
7
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10.1002/ejic.201701176
European Journal of Inorganic Chemistry
FULL PAPER
Scheme 2. Plausible pathway of functioning phenoxazinone
synthase activity of compound 1.
Supporting Information Summary (see footnote on the first page
of this article): The electronic suporting information file contains
synthetic detais for complex 1, X-ray data, theoritical methods and
Figs. S1 and S2. CCDC 1525135 contains the supplementary
crystallographic data for 1.
Theoretical methods
[51]
The hybrid, DFT-based M06-2X method
and the 6-31+G* basis
set has been used in all calculations as implemented in Gaussian-09
[2]. The geometries have been fully optimized and solvent effects
have been taken into account using the Polarizable Continuum
Model (PCM), specifically the integral equation formalism variant
(IEFPCM) [53]. The plots of molecular orbitals and spin densities have
been generated using Gauss View.
Acknowledgements
A.P. would like to thank the University Grant Commission, New Delhi
(Sanction no. PSW-229/15-16) for financial support. The authors are
also thankful to Indian Association for the Cultivation of Science and
Jadavpur University for instrumental facilities.
Table 2. Crystal data and structure refinement for complex 1.
Empirical formula
Formula weight (g mol–1)
Temperature (K)
Wavelength (Å)
Crystal system
Space group
a (Å)
C32H36Br6ClCoN4O12
1242.49
Keywords: Cobalt-catecholate complex • valence tautomerism;
aromatic nucleophilic substitution • mechanistic exploration and DFT
study • phenoxazinone synthase activity
150(2)
0.71073
Monoclinic
P21/c
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FULL PAPER
Arometic
substitution
nucleophilic
Co-bound
Anangamohan Panja, Antonio
Frontera
in
tetrabromocatecholate
ligands
tautomeric
biomimetic
Page No. – Page No.
through
transition
valence
and
Valence tautomerism driven
aromatic nucleophilic substitution
in cobalt-bound
catalysis are reported
tetrabromocatecholate ligands:
Influence of positive charge at
ligand backbone on phenoxazinone
synthase activity
10
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11
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