The first example of a centro-symmetrical bis(imido)-bridged dinuclear cobalt(iii) complex: Synthesis via oxidative dehydrogenation and phenoxazinone synthase activity

Article abstract of DOI:10.1039/c3dt32788d

A bis(imido)-bridged dinuclear cobalt(iii) complex, [Co₂(amp) ₂(μ-imp)₂Cl₂]Cl₂·2H ₂O (1) [amp = 2-aminomethylpyridine; imp = 2-iminomethylpyridine anion], was synthesized by the reaction of cobalt(ii) chloride with 2-aminomethylpyridine in the presence of alkaline hydrogen peroxide at room temperature. X-ray crystallography reveals that both the metal centres in the molecule are related to each other through an inversion centre, and the geometry of each of the Co^III ions is a distorted octahedral structure having a CoN₅Cl coordination environment. The most important feature of the structure is the modification of half of the coordinated amines by the oxidative dehydrogenation process which involves double bridging in the complex cation. To the best of our knowledge, this is the first example of a bis(imido)-bridged dinuclear cobalt(iii) complex derived from metal-assisted oxidative dehydrogenation of the coordinated primary amine ligand. Complex 1 was found to be an excellent functional model for the phenoxazinone synthase, catalyzing the oxidative coupling of 2-aminophenol to the corresponding 2-aminophenoxazinone chromophore in dioxygen saturated methanol. The detailed kinetic investigations reveal that the phenoxazinone chromophore is produced via a potential complex-substrate intermediate.

Full text of DOI:10.1039/c3dt32788d

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The first example of centroꢀsymmetrical bis(imido)ꢀbridged
dinuclear cobalt(III) complex: synthesis via oxidative
dehydrogenation and phenoxazinone synthase activity†
*
,a,b,c
a,b
Anangamohan Panja
and Philippe Guionneau
a
CNRS, ICMCB, Groupe des Sciences Moléculaires, UPR 9048, F-33608 Pessac, France
Université de Bordeaux, ICMCB, UPR 9048, Pessac, F-33600, France
b
c
Postgraduate Department of Chemistry, Panskura Banamali College, Panskura RS, Purba
Medinipur, West Bengal 721152, India
Corresponding Author
Eꢀmail: ampanja@yahoo.co.in
ABSTRACT
2 2 2 2 2 2
A bis(imido)ꢀbridged dinuclear cobalt(III) complex, [Co (amp) (ꢁꢀimp) Cl ]Cl ꢂ2H O (1)
[
amp = 2ꢀaminomethylpyridine; imp = 2ꢀiminomethylpyridine anion], was synthesized by the
reaction of cobalt(II) chloride with 2ꢀaminomethylpyridine in the presence of alkaline
hydrogen peroxide at room temperature. Xꢀray crystallography reveals that both the metal
centres in the molecule are related to each other through an inversion centre, and the
III
geometry of each of the Co ion is a distorted octahedral structure having a CoN
5
Cl
coordination environment. The most important feature of the structure is the modification of
half of the coordinated amines by the oxidative dehydrogenation process which involve in
doubly bridging in the complex cation. To the best of our knowledge, this is the first example
of bis(imido)ꢀbridged dinuclear cobalt(III) complex derived from metalꢀassisted oxidative

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dehydrogenation of the coordinated primary amine ligand. Complex 1 was found to be an
excellent functional model for the phenoxazinone synthase, catalyzing the oxidative coupling
of 2ꢀaminophenol to the corresponding 2ꢀaminophenoxazinone chromophore in dioxygen
saturated methanol. The detailed kinetic investigations reveal that the phenoxazinone
chromophore is produced via a potential complexꢀsubstrate intermediate.
Introduction
Imines are useful intermediates in the synthesis of biologically active nitrogenꢀcontaining
organic compounds and pharmaceutical substances, thus the transition metalꢀpromoted
1
,2
oxidation of amines has attracted extensive attention. Substantial progress has been made in
recent years in the development of oxidation reactions for the synthesis of imines from
secondary amines; notable examples include stoichiometric oxidation with
3
4
N-tertꢀbutylphenylsulfinimidoyl chloride or 2ꢀiodoxybenzoic acid (IBX), metalꢀcatalyzed
t
5
6
oxidation with H
2 2 2 2 8
O , BuOOH, PhIO, or K S O , iridiumꢀcatalyzed dehydrogenation, along
7
ꢀ11
with osmium, ruthenium, cobalt, copper, and iron catalyzed aerobic oxidation.
However,
comparatively little attention has been committed to the oxidation of primary amines,
probably because the corresponding imines usually constitute intermediate products that are
12
rapidly dehydrogenated to nitriles due to the reactivity of the second αꢀamino hydrogen.
Although the oxidative dehydrogenation of amines by the assistance of coordinated metal
centres involving a variety of monoꢀ, biꢀ and multidentate ligands, has been described, the
reports on crystal structures of the concerning imine coordinated metal complexes are
10,11,13
scarce.
Therefore, it remains a challenge to structurally characterize of the
imineꢀcoordinated metal complexes that are expected to disclose some relevant informations
for the further development of metalꢀassisted dehydrogenation of coordinated amines.
The design of dinuclear metal complexes incorporating suitable bridging ligands has
2

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1
4,15
attracted considerable research interest in recent years,
primarily due to their relevance
for biological processes, molecular electronics and for theoretical studies of electron transfer
16ꢀ18
19,20
processes.
As far as biochemistry is concerned, the enzyme phenoxazinone synthase,
a multicopper oxidase is found naturally in the bacterium Streptomyces antibioticus and
catalyzes the oxidative coupling of two molecules of a substituted 2ꢀaminophenol to the
21
phenoxazinone chromophore in the final step for the biosynthesis of actinomycin D. This is
used clinically for the treatment of Wilm’s tumour, gestational choriocarcinoma, and other
22,23
tumors.
The synthesis and investigation of functional model complexes for
metalloenzymes that mimic the oxidase (oxygenase) activity is therefore of great importance
in the development of new and efficient catalysts for oxidation reactions. Only a few
functional models based on cobalt have been reported which show phenoxazinone synthase
2
4
activities.
We have recently reported the study of the catechol oxidase/dioxygenase activity of
mononuclear Cu(II) and iron(III) complexes and also stoichiometric oxidation of
2
5,26
2ꢀaminophenol by a mononuclear cobalt(III) complex.
The catalytic inefficiency of the
reported cobalt(III) complex is mainly due to failure of regeneration of the catalyst during
26
course of the reaction. In order to explore better functional models for the phenoxazinone
synthase, herein, we report the synthesis, physiochemical and spectral properties of the first
structurally
Co (amp)
ꢀiminomethylpyridine anion], derived from the oxidative dehydrogenation of half of the
characterized
bis(imido)ꢀbridged
dinuclear
cobalt(III)
complex,
[
2
2
(ꢁꢀimp) Cl ]Cl ꢂ2H
2
2
2
2
O
(1) [amp
=
2ꢀaminomethylpyridine; imp
=
2
coordinated amine ligand at mild condition (Scheme 1). The synthesized dinuclear complex
shows phenoxazinone synthaseꢀlike activity, and the detailed kinetic investigations
concerning this activity are described.
3

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Experimental section
Materials and physical measurements
Chemicals such as 2ꢀaminomethylpyridine, 2ꢀaminophenol and cobalt(II) chloride
hexahydrate were purchased from Aldrich and Alfa Aesar. All other chemicals and solvents
were of reagent or analytical grade and were used without further purification.
Elemental analyses for C, H, and N were performed in a Thermo Fischer Flash EA1112
–
1
analyzer. The infrared spectra of the sample in KBr disk was recorded in the 400–4000 cm
range on a PerkinElmer Infrared spectrometer. Electrochemical data were collected on an
EG&G Princeton Applied Research potentiostat model 263A with a Pt working electrode,
glassyꢀcarbon electrode, and Ag/AgCl reference electrode. UVꢀvis spectra of the complex
were measured using a PerkinElmer Lamdaꢀ35 spectrophotometer with a 1 cm pathꢀlength
quartzꢀcell. Electrospray ionization mass (ESIꢀMS positive) spectra were recorded on a
MICROMASS QꢀTOF mass spectrometer.
Synthesis of [Co
A mixture of CoCl
mmol) was mixed together in 40 mL of methanol. The resulting red solution was treated with
a mixture of H and NaOH (4.0 mmol) in 1 mL of water with stirring for 10 min at room
2
(amp)
2
2 2 2 2
(ꢁꢀimp) Cl ]Cl ꢂ2H O (1)
2
ꢂ6H O (238 mg, 1.0 mmol) and 2ꢀaminomethylpyridine (216 mg, 2.0
2
2
O
2
temperature, during which time the mixture was turned brownishꢀred. The brown mass of
complex 1 was isolated by evaporation of solvent under reduced pressure. Recrystallization
from methanol afforded crops of brownishꢀred blocks of the complex and were isolated via
suction filtration, washed with diethyl ether, and air dried. Yield: 151 mg (42%). Anal Calcd.
for C24
5.36 %. IR (KBr, cm ): 3448 (br; νOꢀH); 3204 (w; νNꢀH); 3112ꢀ2972 (w; νCꢀH); 1643 (s;
νC=N).
4 2 8 2
H30Cl Co N O : C, 39.91 %; H, 4.19 %; N, 15.51%. Found: C, 40.08 %; H, 4.22 %; N,
–1
1
4

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Xꢀray crystallography
Suitable single crystal of complex 1 was coated with Nꢀparatone oil, picked up with a
nylon fibre and mounted in the cold nitrogen stream operating at 250 K of a Nonius Kappa
CCD diffractometer equipped with a Moꢀtarget rotating anode Xꢀray source and a graphite
monochromator (MoꢀKα, λ = 0.71073 Å). Cell refinement, indexing, and scaling of the data
2
7
set were performed using the programs DENZOꢀSMN and SCALEPACK. The structures
were solved by direct methods and subsequent Fourier analyses, and refined by the
2
fullꢀmatrix leastꢀsquares technique based on F with the SHELXL97 program using all the
2
8
reflections. All the nonꢀhydrogen atoms were refined using anisotropic thermal parameters.
Hydrogen atoms belonging to the complex were placed at calculated positions and refined as
riding atoms with isotropic displacement parameters. All the calculations were performed
2
9
using the WinGX System, Ver. 1.70.01. Crystal data and details of data collection and
refinement for complex 1 are summarized in Table 1. CCDC 883590 contains the
supplementary crystallographic data for complex 1.
Kinetics of the oxidation of 2ꢀaminophenol
The phenoxazinone synthase activity of the dinuclear cobalt(III) complex was studied
by the reaction with 2ꢀaminophenol at 25 ºC in methanol by the UVꢀvis spectroscopy.
Kinetics of the aerobic oxidation of 2ꢀaminophenol catalyzed by complex 1 was measured
3
–1
–1
monitoring change in the absorbance as a function of time at 433 nm (ε = 24 ×10 M cm ),
which is characteristic of 2ꢀaminophenoxazinꢀ3ꢀone in methanol. In a first test series, varying
–5
–2
amounts of the catalyst, (5 − 100) × 10 M, were added to a fixed concentration (1 × 10 M)
–
5
of substrate in methanol (2.0 mL) saturated with dioxygen. In a second test series, 5 × 10 M
solution of the complex was mixed with varying concentrations of substrate (0.5 – 20) mM in
dioxygen saturated methanol (2.0 mL). The initial rate method was applied to determine the
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rate of a reaction, and the average initial rate over three independent measurements was
determined by linear regression from the slope of absorbance versus time plot.
Results and discussion
Synthesis and general characterizations
Reaction of 2ꢀaminomethylpyridine (amp) with cobalt(II) salt generally yields bis(amp)
30
or tris(amp) chelated cobalt(III) complexes by the oxidation of molecular dioxygen. It is
well established that peroxoꢀbridged dinuclear cobalt(III) complexes having various nitrogen
donor ligands are usually formed in aerobic condition which thereafter produces imine
functionalities of the coordinated amines in basic media by the degradation of the
31,32
peroxoꢀintermediate.
In most of cases, an elevated temperature was employed in order to
facilitate such oxidative dehydrogenation of amines. Based on this view, we intended to
produce an imine functionality by the reaction of 2ꢀaminomethylpyridine with cobalt(II)
chloride in alkaline media. The spectra of the resulting blue solution is consistent with the
33
cobalt(II) species (Fig. S1†) and on standing at least for half an hour no significant spectral
modification was noticed. Thus, at the present reaction condition either the reactive
cobaltꢀdioxygen species was not formed or it was relatively weak to assist the oxidative
dehydrogenation of the coordinated primary amine. However, peroxoꢀadducts of cobalt(III)
may be produced by the direct treatment of hydrogen peroxide with cobalt(II) complex in the
3
4
presence of a base at low temperature. It is also reported that an additional oxidant, such as
hydrogen peroxide, is required in some systems to start the reaction and different imines were
produced as a result of the oxidative dehydrogenation reactions. Based on the above
observations, we envisioned that alkaline hydrogen peroxide may produce peroxoꢀadduct of
cobalt(III) complex coordinated to 2ꢀaminomethylpyridine at room temperature, which may
rapidly generate radical species that be responsible for the oxidative dehydrogenation of
coordinated amine. Accordingly, the present bis(imido)ꢀbridged dinuclear cobalt(III) complex
6

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was synthesized by the reaction of cobalt(II) chloride with 2ꢀaminomethylpyridine in 1:2
molar ratio in methanol, followed by treatment with alkaline H in aqueous medium at
2
O
2
room temperature (Scheme 1). Brownishꢀred crystals of complex 1 were isolated by the slow
evaporation of methanol solution in moderate yield. The use of strong alkaline base helps to
deprotonate the resulting imine and to produce the bis(imido)ꢀbridged dinuclear complex.
The complex was characterized by the elemental analysis, and various spectroscopic and
physiochemical methods. The infrared spectral data of the complex are reported in the
Experimental Section with tentative assignments. The IR spectrum of the complex shows a
–1
broad band observed at 3448 cm assigned to solvent water molecules that illustrate the
involvement of strong hydrogen bonding by water molecules in the crystal packing. The most
–1
significant feature of IR spectra is the presence of a band at 1643 cm , attributed to νC=N for
imine functionalities, which is in good agreement with the Xꢀray crystal structure of the
complex (vide infra).
Description of the crystal structure of complex 1
The molecular structure of the dinuclear cobalt(III) complex was determined by single
crystal Xꢀray diffraction technique. Crystallographic data and the details of data collection
and refinement for the complex are assembled in Table 1. The important bond lengths and
angles are summarized in Table 2. The compound crystallizes in the triclinic Pī space group,
where the asymmetric unit corresponds to half of the molecule. The perspective view of
complex cation of 1 along with the selected atom numbering scheme is depicted in Fig. 1.
III
The complex cation is formed by a bis(imido)ꢀbridged Co dimer, and in the molecular
structure two metal centres are related to each other through an inversion centre which bisects
2
Co1 and Co1a and also N4 and N4a. A C rotation about this point of origin transposes the
coordinates of half of the atoms in the molecule to their ‘a’ equivalents. The geometry of each
III
of the Co ion can be best described as a distorted octahedral structure; the CoN
5
Cl
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coordination environment is comprised of two imidoꢀbridged nitrogen atoms, one amine
nitrogen atom, two pyridyl nitrogen atoms, and one chloride ion. Importantly, the imino
III
ligand lies on the same plane along with the Co centre as expected from their electronic
structure, and the maximum deviation from the mean plane defined by
N4−C1−C2−C3−C4−C5−N3 observed for N3 is 0.012 Å. The C−Nimino bond distance of
3
5
1
.263(5) Å, is significantly shorter than the C−Namine bond (1.478(5) Å) as expected. The
Co–Namine, average Co–Nimino, mean Co–Npyridine, and Co–Cl bond lengths are 1.947(3),
1.895(3), 1.965(3) and 2.264(1), respectively, which are in good agreement to those found in
30,36
the related cobalt(III) complexes.
The Co–Nimino bond length is shorter than Co–Namine,
indicating that the deprotonated bridging iminoꢀN coordinates more strongly to the metal
centre than the primary amine group. Average bite angel of the bidentate ligands, 82.54(14)º,
deviates significantly from 90°, which is the main reason for the structural distortion of
complex 1 from the ideal geometry. The intramolecular separation between the two
III
imidoꢀbridged Co centres is 2.925(1) Å, which is comparable to the metalꢀmetal separations
3
7
found in many multinuclear metalloenzymes showing oxidase activity. The molecular
packing of the complex is stabilized by several πꢂꢂꢂπ stacking interactions between the
aromatic rings (Fig. S2†), and the moderately strong hydrogenꢀbonding interactions involving
–
primary amines, solvent water molecules and Cl ions (Table 3).
III
Co ions in mononuclear complexes with 2ꢀaminomethylpyridine have been reported to be
sixꢀcoordinate with octahedral geometry in which the coordinated nitrogen atoms of primary
30
amine was not oxidatively dehydrogenated. In the present complex, the main feature of the
structure is the modification of the coordinated ligand: the C1–N4 distance [1.263(5) Å]
indicates the presence of an imine moiety, which is consistent with the spectroscopic studies
(cf. below). The structure of complex
1
can only be compared with an
III
imidomalonatoꢀbridged binuclear Co complex which was synthesized by the reaction of
8

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[
2 2
CoCl (tren)Cl.H O [tren = tris(2ꢀaminoethyl)amine] with αꢀaminomalonate anion in the
presence of triethylamine at elevated temperature. In the crystal structure, an imidoꢀbridge is
3
5
stabilized by the simultaneous coordination of malonato groups to the metal centres. But in
the present structure, the complex is simply stabilized by the two imidoꢀbridges, and this
remarkable stability arises mainly from the strong Co–Nimino bonding, indicative of the
significant cooperation of two imidoꢀbridges in the molecule. To the best of our knowledge,
complex 1 is the first example of a doubly imidoꢀbridged cobalt(III) complex.
Dehydrogenation of coordinated 2ꢀaminomethylpyridine
Dehydrogenation of the coordinated amine ligand was further established by UVꢀvis and IR
spectroscopic methods. For this purpose, shortly after mixing of cobalt(II) chloride and
2ꢀaminomethylpyridine, the UVꢀvis spectrum of a methanol solution was recorded. It displays
4
an absorption maxima at 252 nm (ε = 5.6 × 10 ) and a shoulder at 368 nm. Upon addition of
an aqueous solution of alkaline hydrogen peroxide, a vigorous reaction had been observed
and ultimately resulted in a dark brown solution. The UVꢀvis spectroscopy reveals that two
4
3
new absorption bands at 344 nm (ε = 1.2 × 10 ) and 541 nm (ε = 2.4 × 10 ) with isobestic
points observed at 282, 381 and 497 nm, clearly supporting the formation of a new product
[
Fig. 2]. The band at 541 nm can be assigned to the deprotonated imine to metal charge
transfer; the facile charge transfer, consistent with the crystal structure of the dinuclear
complex where imine nitrogen atoms are firmly bound to the metal centres. In order to get
further insight into the solution species, the mass spectroscopy (ESI, positive mode) of the
resulting solution was carried out. The base peak at m/z = 307.0298 observed in the mass
+
spectra can be assigned to monocationic halfꢀmolecule of complex 1, [Co(amp)(imp)Cl] ,
confirmed by the isotopic distribution patterns (Fig. S3†). In addition, a weak peak observed
+
at m/z = 613.1391 corresponds to the monocation of dimer, [1–H] , consistent with the
isotopic distribution patterns. The mass spectroscopic results unambiguously suggest that the
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major species produced by the oxidative dehydrogenation of coordinated
2ꢀaminomethylpyridine in solution is 1.
The Infrared spectroscopy is also a good tool for monitoring the conversion of
dehydrogenation of an amine. IR spectrum of a mixture of cobalt(II) chloride and
–1
2
ꢀaminomethylpyridine in 1:2 molar ratio in methanol shows a band at 1613 cm that might
be due to the C=N stretching of pyridyl moieties [Fig. S4†]. Upon addition of the alkaline
hydrogen peroxide the peak was shifted to higher frequency with band maximum at 1640
–1
cm which clearly indicates the conversion of a primary amine to an imine via an oxidative
dehydrogenation process. The ease of oxidative dehydrogenation of the coordinated
2ꢀaminomethylpyridine is probably due to the conjugated structure of the resulting imine,
which is consistent with crystal structure of complex 1. The spectroscopic results, together
with the crystal structure of the complex clearly demonstrate the oxidative dehydrogenation
of the coordinated primary amine to imine functionality ꢀ the metal ion associated with
hydrogen peroxide in basic media plays a significant role in this oxidative dehydrogenation
process. The presence of an alkali metal cation is strong enough to deprotonate the imine
group of coordinated ligands, resulting in a formation of the imidoꢀbridged dinuclear
cobalt(III) complex.
Most of the previous reports on metal ion promoted dehydrogenation of the coordinated
amines by cobalt complexes describe that the key intermediate for the oxidation of amines is
31,32,38ꢀ41
the peroxoꢀadduct of the cobalt(III) complex.
In the presence of a base, cobalt(II)
species activates molecular dioxygen for the catalytic dehydrogenation of the coordinated
amine groups. The elevated temperature was used in most cases to facilitate the
dehydrogenation process. However, similar intermediate may be generated by the treatment
of a coordinatvely unsaturated cobalt complex with hydrogen peroxide in basic medium at
34
low temperature. UVꢀvis spectral data suggest that molecular dioxygen is unable to start
1
0

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oxidative dehydrogenation of the coordinated primary amine, and an external activator, such
as hydrogen peroxide, is required for this chemical transformation (Fig. S1†). As with all the
31,32,38ꢀ41
reported cobalt complexes which show oxidative dehydrogenation of amines,
in the
present study, the peroxoꢀadduct rapidly decomposes and subsequently produces
bis(imido)ꢀbridged dinuclear cobalt(III) complex 1.
Electrochemical studies
The function of a redox active metalloenzyme is to catalyze a redox process; therefore, study
of the electrochemical properties of their models is of profound importance especially at
identical experimental conditions of the kinetic studies. The electrochemical data of the
complex has been recorded in methanol containing 0.1 M tetrabutylammonium perchlorate as
a supporting electrolyte at a glassyꢀcarbon working electrode and using a Ag/AgCl reference
electrode. Cyclic voltammogram of complex 1 shows an electrochemically irreversible peak
at –0.70 V both in aerobic and inert conditions which is assigned to the reduction of the
cobalt(III) centres to cobalt(II) (Fig. 3). The irreversible nature of the electrochemical process
II
may be due to the instability of Co species on the electrode surface presumably by the loss
II
of a labile chloride ion from the coordination sphere. Moreover, the Co species is formed at
a quite negative potential which indicates that complex 1 may not be a suitable catalyst for
oxidation reactions although the regeneration of catalyst is quite favourable in aerobic
condition. An irreversible oxidation response at 0.54 V attributed to the oxidation of
2ꢀaminophenol under identical conditions supports this fact (Fig. S5†). But the
electrochemical scenario of the reactants may be dramatically changed if a catalystꢀsubstrate
adduct is formed during the course of a redox transformation, and in such a situation facile
III
oxidation of the coordinated 2ꢀaminophenol by Co centre through an innerꢀsphere electron
transfer pathway would be possible. In fact, the rate saturation kinetic profile (cf. below)
strongly suggests the formation of complexꢀsubstrate adduct prior to the electron transfer
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process.
Phenoxazinone synthase activity and kinetic studies
The catalytic activity of complex 1 for the oxidation of 2ꢀaminophenol (OAPH) by
molecular O was evaluated spectrophotometrically in dioxygenꢀsaturated methanol at 25 ºC.
2
The reactivity studies were performed in methanol because of good solubility of the complex,
substrate and as well as their product. In order to avoid the autoxidation of the substrate by air
the catalytic activity was checked in absence of added base. Before proceeding into the
detailed kinetic study, it is necessary to check the ability of the complex to oxidize
–5
2
ꢀaminophenol. For this purpose, 5 × 10 M solution of complex 1 was treated with 100
equivalents of OAPH under the aerobic condition. The course of the reaction was followed
by UVꢀvis spectroscopy by monitoring increase in the absorbance at 433 nm, corresponding
to the formation of the phenoxazinone chromophore. Time dependent spectral change for the
period of 2 h after the addition of OAPH to the methanolic solution of the complex is
depicted in Fig. 4. The spectral scan reveals the increase of peak intensity at 433 nm
characteristic for phenoxazinone chromophore formed over time. The product was isolated
after 24 h of reaction, and analyzed by GC, which showed the formation of
2ꢀaminophenoxazineꢀ3ꢀone as the sole product with 100% conversion.
The reaction kinetics of the oxidation of OAPH was determined by the method of initial
rates by monitoring the growth of 433 nm band of the product 2ꢀaminophenoxazineꢀ3ꢀone.
The concentration of the substrate OAPH was always kept at least 10 times higher than that
of the complex to maintain the pseudoꢀfirstꢀorder condition. All the kinetic experiments were
carried out at constant temperature of 25 ºC, monitored with a thermostat. In order to explore
the dependence of the rate on the substrate concentration, a fixed concentration of complex 1
–5
–4
(
5 × 10 M) was treated with varying concentrations of the substrate from 5 × 10 M to 1 ×
–
2
1
0 M, and the formation of 2ꢀaminophenoxazineꢀ3ꢀone was monitored over time at 433 nm.
1
2

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Initial rates were determined by linear regression from the slope of the absorbance versus
time plot for each concentration of the substrate and each experiment was repeated three
times with a variation of ± 4%. The average rate of the reactions show that the rate is first
order at the region of low concentrations of the substrate OAPH while zero order at its higher
concentrations (Fig. 5). This observation indicates that the oxidation of OAPH proceeds
through the formation of a relatively stable intermediate, complexꢀsubstrate adduct,
presumably formed by the coordination of substrate to catalyst by the replacement of a
chloride ion, followed by the irreversible substrate oxidation in the rateꢀdetermining step of
the catalytic cycle. This type of saturation rate dependency on the concentration of the
substrate may be explained by considering MichaelisꢀMenten model, originally developed for
M
the enzyme kinetics. Analysis of the experimental data yielded an equilibrium constant (K )
–3
–7
–1 –1
value of 1. 57 × 10 and Vmax value of 1.91 × 10 M s ; these are also verified by the
Lineweaver–Burk plot. The kcat value is obtained by dividing the Vmax by the concentration of
–3
–1
–1
the complex used, and is found to be 3.82 × 10 s . Although the turnover rate of 13.75 h
is moderate enough, reactivity of which cannot be compared to the reported functional
models of phenoxazinone synthase as most of the cases turnover numbers are not
4
2,43
evaluated.
Moreover, for a particular substrate concentration, varying the complex
concentration, a linear relationship for the initial rates was obtained, which shows a
firstꢀorder dependence on the complex concentration (Fig. S6†). Based on the above results, a
possible mechanism OAPH oxidation catalyzed by complex 1 is proposed (Scheme 2). At the
first step OAP forms an adduct with the dinuclear cobalt(III) complex, which yields OAP
radical in the rate determining step. The OAP radical may generate oꢀbenzoquinone
monoamine (BQMI) in many ways including the disproportionation of the OAP radical itself.
Ultimately, 2ꢀaminophenoxazineꢀ3ꢀone is produced via several oxidative dehydrogenation
2
processes involving OAPH, O , and BQMI as shown in Scheme 2.
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Conclusions
A dinuclear cobalt(III) complex was synthesized by the oxidative dehydrogenation of
coordinated 2ꢀaminomethylpyridine in the presence of alkaline hydrogen peroxide. The Xꢀray
crystal structure reveals an unprecedented bis(imido)ꢀbridged dinuclear cobalt(III) complex
in which both the octahedrally coordinated metal centres are related to each other through an
inversion centre. The spectroscopic results suggest that the alkaline hydrogen peroxide plays
a significant role in the oxidative dehydrogenation of the amine at mild condition. The
complex was found to be an excellent functional model of phenoxazinone synthase,
catalyzing the oxidative coupling of 2ꢀaminophenol to the corresponding phenoxazinone
chromophore in dioxygen saturated methanol medium via a catalystꢀsubstrate intermediate.
Apically coordinated labile chloride ion apparently helps to the formation of a
catalystꢀsubstrate intermediate, and thereby, increases the catalytic efficiency of the complex.
The metalꢀmetal separation in the molecule of 2.925 Å is comparable to the separations found
in many multinuclear metalloenzymes, and thus the present report would encourage the
chemists for the synthesis of imidoꢀbridged diꢀ or multiꢀnuclear complexes for the
development of functional models of various metalloenzymes.
Acknowledgements
The author is grateful to the University Grants Commission, India for the financial support of
this research (Sanction No. PSWꢀ173/11ꢀ12). The instrumental facility from Jadavpur
University, India is also gratefully acknowledged.
†
Electronic supplementary information (ESI) available: The electronic supplementary
information file contains Figs. S1–S6. CCDC 883590 contains the supplementary
crystallographic data for complex 1. For ESI and crystallographic data in CIF or other
electronic format see DOI:
1
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Table 1. Crystal data and structure refinement of dinuclear complex 1
Empirical formula
Formula weight
Temperature (K)
Wavelength (Å)
Crystal system
Space group
a (Å)
C H Cl Co N O
24 30 4 2 8 2
722.22
250(2)
0.71073
Triclinic
Pī
8.5370(10)
8.9420(10)
10.680(2)
70.914(6)
75.052(6)
75.559(7)
732.14(18)
2
b (Å)
c (Å)
α
(º)
β(°)
(º)
γ
3
Volume (Å )
Z
–
3
D
calc (g cm )
1.638
–1
Absorption coefficient (mm )
F(000)
1.536
368
Crystal size (mm)
0.10 × 0.0 5 × 0.03
4.12 – 26.37
θ Range for data collection (°)
Limiting indices
–01 ≤ h ≤ 8,
–
–
11 ≤ k ≤ 11,
13 ≤ l ≤13
Reflections collected / unique
Indipendent reflection / Rint
Observed reflections
4893
2970 / 0.0493
2046
Completeness to 2θ (%)
Data / restraints / parameters
Goodnessꢀofꢀfit on F2
99.1
2970 / 0/ 181
1.011
Final R indices [I>2σ(I)]
R1 = 0.0478,
wR2 = 0.1046
R1 = 0.0832,
wR2 = 0.1187
0.937/–0.436
R indices (all data)
–3
Largest diff. peak / hole (e Å )
1
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Table 2. Selected bond lengths (Å) and bond angles (º) for 1
Co1 – N1
Co1 – N2
Co1 – N3
Co1 – Co1#
1.981(3)
1.947(3)
1.950(3)
2.9255(11)
Co1 – N4
Co1 – N4#
Co1 – Cl1
1.884(3)
1.907(3)
2.2645(11)
N4 – Co1 – N1
N4 – Co1 – N1#
N2 – Co1 – N1
N3 – Co1 – N1
N4 – Co1 – N2
N4 – Co1 – N2#
N4 – Co1 – N3
N4 – Co1 – N3#
173.84(13)
96.72(13)
82.10(14)
100.25(14)
93.40(13)
89.93(13)
83.98(14)
162.98(14)
N2 – Co1 – N3
N4 – Co1 – N4#
N4 – Co1 – Cl1
N4 – Co1 – Cl1#
N2 – Co1 – Cl1
N3 – Co1 – Cl1
N1 – Co1 – Cl1
Cl1 – Co1 – Co1#
91.04(14)
79.00(14)
90.97(10)
92.37(10)
175.38(10)
87.93(10)
93.64(10)
92.17(4)
Symmetry Code: # = 1–x, –y, 1–z
Table 3. Important hydrogen bonds (Å, º) for dinuclear complex 1
D–HꢂꢂꢂA
D–H
0.91
1.00
0.94
HꢂꢂꢂA
DꢂꢂꢂA
<D–HꢂꢂꢂA
N2–H2BꢂꢂꢂCl2#
O2–H2OꢂꢂꢂCl2
O2–H1OꢂꢂꢂCl2#
2.302(2)
2.239(2)
2.295(2)
3.166(4)
3.234(5)
3.219(5)
158.3(2)
173.7(3)
167.4(3)
Symmetry Code: # = 1–x, –y, 1–z
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N
Cl
H N
2
Cl NH2
N
N
H O / NaOH
2
2
N
Co
Cl
N
N
MeOH
N
NH2
Cl
N
NH2
Complex 1
Scheme 1. Schematic representation of synthesis of the dinuclear complex
Scheme 2. Probable mechanism for the formation of phenoxazinone chromophore
2
0

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Figure 1: ORTEP diagram of complex cation 1 showing the atom numbering scheme,
ellipsoids are drawn at the 50% probability level. H atoms are omitted for clarity. Symmetry
Code: a = 1–x, –y, 1–z
2
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Figure 2. UVꢀvis spectra of cobalt(II) chloride with 2ꢀaminomethylpyridine in 1: 2 molar
ratio in methanol (dashed line) and upon addition of alkaline hydrogen peroxide (solid line).
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Figure 3. Cyclic voltammogram of the complex in methanol containing TBAP as supporting
electrolyte at a scan rate of 100 mV/s.
2
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Figure 4. Time resolved UVꢀvis spectral changes for the oxidation of 2ꢀaminophenol (5 ×
–
3
–3
–5
–3
10
mol dm ) catalyzed by the complex (5 × 10 mol dm ) up to 2 h of reaction in
dioxygenꢀsaturated methanol at 25 ºC.
2
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Figure 5. Plot of the initial rates on the OAPH concentrations for the oxidation reaction
catalyzed by the complex at fixed concentration in dioxygenꢀsaturated methanol at 25 ºC.
Inset shows the reciprocal LineweaverꢀBurk plot.
2
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Graphical Abstract
The first example of centro-symmetrical bis(imido)-bridged dinuclear cobalt(III)
complex: synthesis via oxidative dehydrogenation and phenoxazinone synthase activity
Anangamohan Panja and Philippe Guionneau
An unprecedented bis(imido)-bridged dinuclear Cobalt(III) complex derived from the
oxidative dehydrogenation of the coordinated primary amine is reported. The phenoxazinone
synthase like activity of the complex is also described.