Synthesis, structure and diverse coordination chemistry of cobalt(III) complexes derived from a Schiff base ligand and their biomimetic catalytic oxidation of o-aminophenols

Article abstract of DOI:10.1016/j.poly.2019.02.024

This paper deals with the syntheses and structural characterizations of four new cobalt(III) compounds (1–4) derived from a N₃O donor Schiff base ligand and their catalytic activity towards the aerobic oxidation of o-aminophenols. Both counter

Full text of DOI:10.1016/j.poly.2019.02.024

Accepted Manuscript
Synthesis, structure and diverse coordination chemistry of cobalt(III) complexes
derived from a Schiff base ligand and their biomimetic catalytic oxidation of
o-aminophenols
Narayan Ch. Jana, Moumita Patra, Paula Brandão, Anangamohan Panja
PII:
S0277-5387(19)30125-1
https://doi.org/10.1016/j.poly.2019.02.024
POLY 13768
DOI:
Reference:
Polyhedron
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Revised Date:
Accepted Date:
11 November 2018
10 February 2019
13 February 2019
Please cite this article as: N.C. Jana, M. Patra, P. Brandão, A. Panja, Synthesis, structure and diverse coordination
chemistry of cobalt(III) complexes derived from a Schiff base ligand and their biomimetic catalytic oxidation of o-
aminophenols, Polyhedron (2019), doi: https://doi.org/10.1016/j.poly.2019.02.024
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Synthesis, structure and diverse coordination chemistry of
cobalt(III) complexes derived from a Schiff base ligand and their
biomimetic catalytic oxidation of o-aminophenols
Narayan Ch. Jana,a‡ Moumita Patra,a‡ Paula Brandão,b and Anangamohan Panja*a
a
Postgraduate Department of Chemistry, Panskura Banamali College, Panskura RS, WB
721152, India
b
Department of Chemistry, CICECO-Aveiro Institute of Materials, University of Aveiro,
3810-193 Aveiro, Portugal
*Corresponding Author
E-mail: ampanja@yahoo.co.in
‡ These authors contributed equally to this work.
This paper deals with the syntheses and structural characterizations of four new cobalt(III)
compounds (1–4) derived from a N3O donor Schiff base ligand and their catalytic activity
towards the aerobic oxidation of o-aminophenols. Both counter ions and solvents used for the
synthesis have significant influence on structural diversity of the resulting complexes. X-ray
crystallography reveals that although the geometry of cobalt(III) centres are octahedral in all
the cases but the coordination environments are significantly different in them. All these
complexes show diverse reactivity towards the catalytic oxidation of o-aminophenols in
which availability of substitutaionally labile sites at the metal centre for substrate o-
aminophenols binding is the main reason for higher catalytic activity in 2 and 3 than others.
Furthermore, we have examined the detailed kinetic studies of the aerobic oxidation of one
substituted o-aminophenol, namely 2-amino-5-methylphenol, using 2 and 3 as catalysts in

which facile oxidation of the substituted o-aminophenol was noticed. ESI mass spectral study
has been carried in order to get insight into mechanistic pathway of functioning such catalytic
activity.
Keywords: Cobalt complexes, Structural diversity, Influence of coordination sphere on
catalytic activity, Phenoxazine chromophores, Mass spectrometry and proposed mechanism
1. Introduction
Most of the industrial oxidation processes for the synthesis of various organic chemicals
including the manufacture of large-scale pharmaceutical compounds use permanganate,
dichromate and heavy metal oxides as oxidants, leading to the environmental pollution [1,2].
However, in the natural oxidation process, dioxygen is used as sole oxidant for the
biocatalytic oxidation of various biologically important organic compounds where the
metalloenzymes activate dioxygen [311]. Therefore, the biomimetic studies of these
metalloenzymes could provide us valuable catalysts for in vitro synthesis of various organic
compounds using dioxygen as a primary oxidant [12−16]. Further studies with these
biomimetic models may help for better understanding of the mechanistic aspects occurring at
the active site of the metalloenzymes [17−23]. Though a decent effort has been made by the
bioinorganic chemists in unravelling the catalytic mechanism of action of these enzymes by
means of a synthetic analogue approach, [24−26] further mechanistic studies are required for
developing alternative pathways to form same products.
We have been developing biomimetic catalysts for the oxidation of 3,5-di-tert-
butylcatechol [27−29] and o-aminophenol [30,31] by molecular dioxygen mimicking the
function of catechol oxidase and phenoxazinone synthase, respectively. Transition metal
complex mediated oxidative coupling of o-aminophenol to 2-aminophenoxazinone through
catalytic activation of dioxygen has been considered as an important reaction [32−34]
2

because of the presence of 2-aminophenoxazinone chromophore in actinomycin D, a
naturally occurring antibiotic [35]. Actinomycin D is among the most potent antineoplastic
agents known to inhibit DNA directed RNA synthesis [36,37]. It is used for the treatment of
some kind of cancers of the bones and soft tissues like choriocarcinoma, testis, Wilms’
tumor, rhabdomyosarcoma, Kaposi’s sarcoma and Ewing’s sarcoma [38]. Although
biological activity of actinomycin was elucidated, other phenoxazine derivatives have not
been examined well. Recently, Tomoda and co-workers were examined the anti-bacterial
effects of Phx-1 (2-aminophenoxazinone), Phx-2 (2-amino-4,4a-dihydro-4a-7-dimethyl-3H-
phenoxazinone) and Phx-3 (3-amino-1,4a-dihydro-4a-8-dimethyl-2H-phenoxazinone)
(Scheme 1), which are produced by the reaction of o-aminophenol or its derivatives with
bovine hemoglobin [39]. Thus, the chemistry of phenoxazine derivatives has to be further
explored. The active site structures of the metalloenzymes and their efficient synthetic
models [28−35,40−48] disclose that the redox flexibility of the metal centers and the labile
position(s) at metal sites are crucial factors behind their efficient activities. Therefore, the
ligands with fewer donor sites are more suitable for the development of efficient synthetic
analogues.
The coordination chemistry of N,N-dimethyldipropylenetriamine is almost unexplored,
[49] and we recently reported a series of Ni(II) and Co(III) complexes [50] with Schiff base
ligands resulting from this triamine with substitutionally labile coordination sites in most
cases. In continuation of our research interest, [27−31] we report, herein, the synthesis and
structures of four new cobalt complexes, [Co(HL)2](ClO4)3·2H2O (1), [Co(L)(N3)2] (2),
[Co(L)(NCS)2] (3), and [Co(L)(Br-sal)]2[Co(NCS)4] (4) (where HL is a Schiff base ligand as
shown in scheme 2 and Br-salH is 5-bromosalicylaldehyde), and their biomimetic catalytic
activity using the substrates o-aminophenol and 2-amino-5-methylphenol by molecular
dioxygen. Remarkable influence of solvents and counter ions leading to the diverse
3

coordination chemistry of cobalt was observed. Further emphasis was given to ESI mass
spectral study to get insight into the mechanism of action of such catalytic activity.
Scheme 1: Chemical structures of Phx-1, Phx-2, and Phx-3.
4

Scheme 2. Schiff base HL and synthetic scheme.
2. Experimental section
2.1 Materials and physical measurements
Cobalt(II) nitrate hexahydrate, cobalt(II) perchlorate hexahydrate, o-aminophenol (OAPH),
5-bromosalicylaldehyde (Br-salH), and N,N-dimethyldipropylenetriamine were of
commercially available reagent or analytical grade chemicals and were used as received. 2-
amino-5-methylphenol was purchased from Alfa Aesar. Other chemicals and solvents were
of reagent grade and used without further purification.
Caution! Metal perchlorate and azide salts are potentially explosive. Although no problem
was encountered in the present study, use of small amounts of the materials with great
precaution is recommended.
CHN (carbon, hydrogen and nitrogen) analysis were performed using a Perkin-Elmer
240C elemental analyser. Electronic absorption spectra were recorded using an Agilent
Carry-60 diode array UV-Vis spectrophotometer at room temperature with a 1-cm path-
length quartz cell. IR spectra were performed in a PerkinElmer Spectrum Two FTIR
spectrophotometer in the range 400 to 4000 cm–1 with the samples prepared as KBr pellets.
Electrochemical studies were performed using tetrabutylammonium perchlorate as a
supporting electrolyte in methanol on a CH Instrument electrochemical workstation model
CHI630E, with the conventional three-electrode assembly comprising of a platinum working
electrode, a platinum wire auxiliary electrode and a Ag/AgCl reference electrode.
Electrospray ionization mass spectral (ESI-MS positive) study were conducted in a
Micromass Q-tof-Micro Quadruple mass spectrometer. 1H NMR spectra were measured using
a Bruker 300 spectrometer in DMSO-d6. Magnetic susceptibility measurement was carried
out on a PAR 155 vibrating sample magnetometer at room temperature.
5

2.2 Synthesis of the Schiff-base ligand (HL)
A mixture of 1.0 mmol of N,N-dimethyldipropylenetriamine (159 mg) and 1.0 mmol of 5-
bromosalicylaldehyde (166 mg) in 20 ml of methanol was heated to reflux for about 1 h,
turning down a dark yellow solution. The solvent was removed under reduced pressure that
resulted dark yellow crude oily ligand. The same was extracted with dichloromethane and the
solvent was removed under reduced pressure that resulted finally the dark yellow liquid
ligand with desired purity. Anal. Calcd. for C30H52Br2Cl3CoN6O16: C 52.64%, H 7.07%, N
12.28 %. Found: C 51.37%, H 7.28%, N 12.03 %. FTIR (KBr, cm–1): ν(C=N) 1635 s;
ν(NH/OH) 3326 br.
2.3 Synthesis of [Co(HL)2](ClO4)3·2H2O (1)
A methanol solution of cobalt(II) perchlorate hexahydrate (366 mg, 1.0 mmol) was added to a
methanol (20 ml) solution of the Schiff base ligand HL (2.0 mmol) with stirring. Instantly the
solution became dark-brown colour and it was further stirred in air for 1 h. The reaction
mixture was filtered and left undisturbed for slow evaporation of solvent. Dark-brown colour
crystals suitable for X-ray diffraction were separated out from the solution at ambient
temperature within few days, which were collected by filtration and washed with
methanol/ether and air dried. Yield: 866 mg (81 %). Anal. Calcd. for C30H52Br2Cl3CoN6O16:
C 33.52%, H 4.88%, N 7.82 %. Found: C 33.67%, H 4.78%, N 7.63 %. FTIR (KBr, cm–1):
ν(C=N) 1624 s; ν(ClO4) 624 s, 1080 s.
2.4 Synthesis of [Co(L)(N3)2] (2)
Cobalt(II) nitrate hexahydrate (291 mg, 1.0 mmol) in 20 ml of methanol was added to the
Schiff base ligand HL (1.0 mmol) solution with stirring, which instantaneously produced a
dark-brown solution. The mixture was further stirred in air for 30 min, and to this solution
6

sodium azide (130 mg, 2.0 mmol) in methanol/water (5 ml, 4:1 v/v) was slowly added with
stirring. The resulting solution was allowed to reflux for about 30 min and it was then filtered
and kept at ambient temperature for slow evaporation, which afforded X-ray diffraction
quality dark-brown crystals after few days. These crystals were collected by filtration and
washed with methanol/ether and air dried. Yield: 373 mg (77 %). Anal. Calcd. for
C15H23BrCoN9O: C 37.21%, H 4.79%, N 26.03 %. Found: C 37.29%, H 4.60%, N 25.91 %.
FTIR (KBr, cm–1): ν(N3) 2032 vs; ν(C=N) 1618 s.
2.5 Synthesis of complex [Co(L)(NCS)2] (3)
Complex 3 was synthesized from acetonitrile/water (20:1, v/v) mixture adopting the identical
procedure as described for 2, except that NaSCN was used instead of NaN3. Colour: Dark
brown, Yield: 387 mg (75%). Anal. Calcd. for C17H23BrCoN5OS2: C 39.54 %, H 4.49%, N
13.56 %. Found: C 39.63%, H 4.40%, N 13.49 %. FTIR (cm–1, KBr): ν(NCS) 2065 s, ν(C=N)
1625 s.
2.6 Synthesis of complex [Co(L)(Br-sal)]2[Co(NCS)4] (4)
Complex 4 was synthesized from methanol/water (20:1, v/v) mixture following same
procedure as that applied for the synthesis of 2, but NaSCN was used in place of NaN3.
Colour: Dark brown, Yield: 343 mg (69%). Anal. Calcd. for C48H54Br4Co3N10O6S4: C
38.65%, H 3.65%, N 9.39 %. Found: C 38.69%, H 3.57%, N 9.30%. FTIR (cm–1, KBr):
ν(NCS) 2063 s, ν(C=N) 1623 s.
2.7 X-ray crystallography
Suitable single crystals for all complexes were chosen for X-ray diffraction, and the data
were collected on a Bruker SMART APEX-II CCD X-ray diffractometer, which is equipped
with a graphite-monochromated Mo Kα (λ = 0.710 73 Å) radiation by the ω-scan method.
Data integration, reduction, and space group determination were performed using using the
SAINT-plus software, and the absorption correction was made by multi-scan method using
7

SADABS program [51]. The structures were solved using the direct method and refined by
the successive full-matrix least-squares cycles on F2 using SHELXL-v.2013 or SHELXL-
v.2014 [52]. Anisotropic refinement was performed for all non-hydrogen atoms while the
hydrogen atoms placed on carbon atoms were refined using fixed geometry and riding
thermal parameters. The hydrogen atoms associated with nitrogen atoms were located on the
difference Fourier map and isotropically treated with fixed thermal parameters equivalent to
1.2 times of the parent atoms. All the crystallographic diagrams for 1–4 were generated with
the MERCURY-3.10.1 software. Information regarding the X-ray diffraction data collection
and structure refinements of the compounds is given in Table 1.
Table 1. Crystallographic data and structure refinement parameters of 1 to 4
1
2
3
4
Empirical formula
Formula weight (g mol–1)
Crystal system
Space group
C30H46Br2Cl3CoN6O16 C15H23BrCoN9O C17H23BrCoN5OS2
C48H54Br4Co3N10O6S4
1487.70
1071.83
Monoclinic
C2/c
484.26
516.36
Monoclinic
P21/c
Monoclinic
P21/c
Monoclinic
C2/c
a (Å)
20.3477(18)
13.8596(13)
16.2643(14)
90
11.5230(2)
9.2719(2)
18.9789(4)
90
10.2789(6)
13.1774(7)
15.6068(9)
90
11.4638(3)
23.0995(7)
21.5616(7)
90
b (Å)
c (Å)
(°)
107.420(3)
90
106.2820(10)
90
93.700(3)
90
99.484(2)
90
 (°)
(°)
volume (Å3)
4376.3(7)
4
1946.38(7)
4
2109.5(2)
4
5625.6(3)
4
Z
Dcalc (mg m‒3)
µ (mm‒1)
1.625
1.653
1.626
1.757
2.473
2.961
2.923
3.198
F(000)
1908
984
1048
2972
2.625–27.219
40409
1.841–27.922
17294
1.985–26.443
14714
1.763–27.152
43974
 Range (°)
Reflections collected
Independent reflections (Rint)
Observed reflections [I>2(I)]
Restraints/parameters
Goodness-of-fit on F2
Final R indices [I>2(I)]
4788(0.0621)
4357
4654(0.0412)
3727
4328(0.0628)
2865
6243(0.0505)
5101
2/246
0/250
0/250
0/355
1.119
1.028
1.006
1.129
R1 = 0.1401
wR2 = 0.2934
R1 = 0.1482
wR2 = 0.2978
R1 = 0.0392
wR2 = 0.0892
R1 = 0.0551
wR2 = 0.0964
1.457/ –0.660
R1 = 0.0408
wR2 = 0.0784
R1 = 0.0822
wR2 = 0.0910
0.596/ –0.649
R1 = 0.0464
wR2 = 0.0920
R1 = 0.0607
wR2 = 0.0965
1.293/ –0.849
R indices (all data)
Largest diff. peak/hole (e Å‒3) 2.074/ –1.856
8

2.8 Catalytic oxidation of o-aminophenols
The phenoxazinone synthase like activity was carried out by the reaction of 1.0 × 10−2 M of
o-aminophenol with 5 × 10–5 M of the complexes (1–4) in air saturated methanol at room
temperature. Similarly, the oxidation reaction of 2-amino-5-methylphenol (0.5–1.0 × 10−2 M)
was studied with 2 or 3 (1.0–5.0 × 10−5 M) in methanol. Kinetics of the aerobic oxidation of
OAPH catalysed by 1–4 was investigated monitoring increase of the absorbance as a function
of time at 435 nm, which is characteristic absorption band of 2-aminophenoxazinone in
methanol. Similarly, the absorbance versus wavelength plots were generated for the reaction
mixtures of substituted aminophenol and 2 (or 3) by recording spectrophotometric data at a
regular time interval of 5 min. The rate dependency on the substrate concentration was
checked by the reaction of 1 × 10−5 M solution of the complexes with varying concentration
of the substrate maintaining the pseudo-first-order condition All the kinetic measurements
were carried out for a period of 10 min and the initial rate of the reaction was evaluated by
the linear regression from slope of the absorbance verses time plot. Finally, various kinetic
parameters were evaluated applying Michaelis–Menten model.
3. Results and Discussion
3.1 Syntheses and general characterizations
The ligand HL employed in the present study was synthesized by the Schiff base
condensation
reaction
between
5-bromosalicylaldehyde
and
N,N-
dimethyldipropylenetriamine in a 1: 1 molar ratio in refluxing methanol (Scheme 2). The
Schiff base was isolated as an oily mass and that has been characterized by elemental
9

analysis, IR spectroscopy (vide supra) and NMR spectroscopy (see Fig. S1). This Schiff base
ligand by the reaction with cobalt(II) perchlorate hexahydrate in a 2:1 molar ratio afforded
[Co(HL)2](ClO4)3·2H2O (1) in high yield. Again this Schiff base ligand upon reaction with
–
cobalt(II) nitrate hexahydrate together with pseudohalides (N3 for 2, NCS– for 3 and 4) in a
1:1:2 molar ratio produced [Co(L)(N3)2] (2), [Co(L)(NCS)2] (3) and [Co(L)(Br-
sal)]2[Co(NCS)4] (4), in high yields. All the above reactions are not dependent on
stoichiometric ratios of the reactants, but significant influence of the solvents on product
formation was observed. The reaction of the Schiff base ligand, cobalt nitrate hexahydrate
and sodium thiocyanate in acetonitrile/water mixture resulted only isolable product 3; but
same reaction when carried out in methanol/water mixture only compound 4 was isolated in
high yield. Following the same synthetic procedure, isolation of two different kinds of
products clearly suggests that both of them are thermodynamic products where the relative
stabilities in a particular solvent system governs the identity of the species that crystallizes
from that solvent. Interestingly, compound 3 can be converted to complex 4 by prolong
reaction in methanol/water mixture, which was further accelerated by the addition of Br-sal
externally. As found in most of the Schiff base ligands with phenolic group, cobalt(II) centre
is air-oxidized to cobalt(III) when it is bonded to the Schiff base. Some of the compounds
have been characterized by NMR spectroscopy and the NMR data nicely agree with
coordination of the Schiff base ligand to cobalt(III) metal centre (Figs. S2-S4).
The IR spectra of all complexes consist of sharp distinct bands due to stretching
vibrations of the azomethine bond of the Schiff base appearing in the range 1615–1626 cm–1.
Additionally, the presence of a shoulder at around 1650 cm–1 is consistent with the C=O
stretching frequency of the coordinated 5-bromosalicylaldehyde ion in 4. Moreover, broad
absorption bands at around 1080 and 624 cm−1 characteristics of the stretching and bending
vibrations of perchlorate anion, respectively, are observed in the IR spectrum of complex 1
10

−
[53]. The broadening of ν(Cl–O) band hints the participation of ClO4 ions in the hydrogen
bonding interactions in the solid-state. In the IR spectrum of complex 2, a strong absorption
band is appeared at 2032 cm–1, which is typical for stretching band of azide ion [54]. Bands at
2085 cm–1 and 2063 cm–1, assignable to the stretching vibration of thiocyanate ions, are
customarily noticed in the IR spectra of complex 3 and 4, respectively [50a,57]. The better 
acceptor ability of thiocyanate ion from cobalt(II) centre in 4 compared to its  acceptor
ability from cobalt(III) in 3 is reflected from the relative stretching frequencies of thiocyanate
ions in these complexes.
3.2 Structural descriptions
Single crystal X-ray diffraction studies were performed to determine the crystal structures of
all complexes. The crystal structure of complex cation 1 together with selected atom
numbering scheme is depicted in Fig. 1, while the molecular views of 2 and 3 are shown in
Fig. 2, and Fig. 3 represents the crystal structure of 4. The crystallographic parameters related
to important bond distances around the metal coordination sphere for all structures are
assembled in Table 2. Complex 1 crystalizes in the monoclinic C2/c space group where the
complex cation of 1 sits on an inversion centre along with three non-coordinating disordered
perchlorate anions, one of them residing on a two-fold rotation axis. The structure of the
complex cation of 1 is a distorted octahedron in which two zwitterionic forms of the Schiff
bases was coordinated to the metal centre. Each ligand coordinates the metal centre facially
using one phenolate−O atom and two nitrogen atoms (one each of imine and secondary
amine). The presence of zwitterionic form of Schiff base ligand is confirmed by the electro-
neutrality of the system. The average Co−O and Co−N bond lengths are 1.889(6) and
1.986(7) Å, respectively, which are in good agreement with reported low spin octahedral
cobalt(III) complexes [53,56,57].
11

Both 2 and 3 are neutral complexes and crystalize on general positions in the
monoclinic P21/n space groups. The crystal structure determination reveals that the geometry
of the cobalt(III) centre is a distorted octahedral as reflected from slight deviation of cisoid
(84.68(12)–93.66(11)°) and transoid (174.58(13)–177.14(13)°) angles from the ideal values.
The structural features are similar in both cases where the phenolate-O and three nitrogen
atoms (one each of imine, secondary amine and tertiary amine nitrogen atoms) of
monoanionic Schiff base ligand together with two nitrogen atoms from two terminal azide (in
2) and thiocyanate (in 3) ions are bonded to the metal centre. Whereas three nitrogen atoms
from triamine part of the Schiff base ligand occupy one meridional position, other meridional
position is connected with two nitrogen atoms of pseudohalides and the phenolate-O atom of
the Schiff base (Fig. S5). The Co–N(pseudohalide) and Co–O(phenolate) distances of the
Schiff base ligand vary in the range 1.905(3)–1.961(3) and 1.874(2)–1.893(2) Å,
respectively, and are comparable to reported low-spin octahedral cobalt(III) complexes
[53,56,57]. The Co–N bond distances of imine, secondary and tertiary amines fall in the
range 1.931(2)–1.933(3), 1.984(3)–2.001(3) and 2.084(3)–2.107(3) Å, respectively, in both
complexes. The secondary amine bond is found somewhat longer than the imine nitrogen that
is in agreement with their state of hybridisations. The presence of two methyl groups in
tertiary nitrogen atom reduces Lewis basicity of the donor nitrogen atom, leading to the
significantly longer bond distances of the tertiary amine in these complexes [50]. The solid-
state stability of 2 is mainly governed by the hydrogen bonding interaction between
secondary amine and one terminal nitrogen atom of coordinated azide ion from an adjacent
molecule (Fig. 4). Further stability of the solid-state architecture of 2 is provided by the C–
H∙∙∙ interactions involving adjacent molecules. Similar kind of hydrogen bonding interaction
is also observed in the solid-state structure of complex 3 in which the secondary amine forms
hydrogen bond with the sulphur atom of coordinated thiocyanate ion from a neighbouring
12

molecule. Contribution from multiple C–H∙∙∙ interaction involving two adjacent molecules
is also noteworthy for overall stability of the solid-state structure of 3 (Fig 5).
Table 2. Important bond distances (Å) for complexes 1–4.
Bond
1
2
3
4
Co(III)–N(imine)
1.949(8)
2.021(8)
–
1.931(2)
2.001(3)
2.084(3)
1.893(2)
1.933(3)
1.984(3)
2.107(3)
1.874(2)
1.930(3)
2.005(3)
2.091(3)
1.888(3)
1.884(3)
1.910(3)
Co(III)–N(secondary amine)
Co(III)–N(tertiary amine)
Co(III)–O(phenolate)
1.887(7)
Co(III)–O(free aldehyde)
Co(III)–N(pseudohalide)
Co(II)–N(pseudohalide)
1.961(3)
1.952(3)
–
1.916(3)
1.905(3)
–
1.960(4)
1.947(4)
Fig. 1. Molecular structure of the complex cation of 1 with selected atom numbering scheme.
The counter anions and water molecules were omitted for clarity the counter anions and water
molecules were omitted for clarity. Thermal ellipsoids are drawn at 30% probability.
13

2
3
Fig. 2. Crystal structures of 2 and 3 showing selected atom numbering schemes. Thermal
ellipsoids are drawn at 30% probability.
Fig. 3. A partial crystal structure of [Co(L)(Br-sal)]2[Co(NCS)4] (4) with selected atom
labelling scheme. One of the symmetry-related complex cations is omitted for clarity.
Ellipsoids are drawn in 30% probability.
14

Fig. 4. A part of packing diagram showing hydrogen bonding and C–H··· interactions in 2
Fig. 5. A part of crystal packing of 3 displaying hydrogen bonding and C–H··· interactions.
Complex 4 crystalizes in the monoclinic C2/c space group in which the asymmetric unit
includes a complete set of the complex cation of composition [Co(L)(Br-sal)]+ on general
2–
position and a half of Co(NCS)42– unit on a two-fold axis. The geometry of Co(NCS)4 is a
distorted tetrahedral in which thiocyanate ions coordinate cobalt(II) centre through the
nitrogen atoms [56−60]. The oxidation state of cobalt in Co(NCS)42– is further ensured by the
15

room temperature magnetic study which results the magnetic moment value of 4.03 B.M,
consisting with cobalt(II) center in tetrahedral geometry. The bond angles (N–Co–N) varying
in the range 101.0(2)–112.1(2)º support the distorted tetrahedral structure of the complex
anion. In complex cation [Co(L)(Br-sal)]+, the geometry of cobalt(III) centre is best described
as a distorted octahedral structure and it is coordinated by one deprotonated Schiff base
ligand and a 5-bromosalicylaldehyde ion resulting from the hydrolysis of the Schiff base
during complexation process. Like complexes 2 and 3, the Schiff base ligand also coordinates
the metal centre in the tetradentate fashion. The Co–N bond distances of imine, secondary
and tertiary amines are 1.930(3), 2.005(3) and 2.091(3) Å, respectively, which are
comparable to bond distances observed in 2 and 3 and also in the reported low-spin
octahedral cobalt(III) complexes with similar coordination environments [53,56,57]. The Co–
O (phenolate) and Co–O (Br-sal) bond distances are 1.888(3), 1.884(3) and 1.910(3),
respectively, which are also comparable to the literature data. The Co–N bond distances
associated with amine and imine nitrogen atoms are similar as that found in 2 and 3. Different
types of noncovalent interactions like hydrogen bonding and C–H∙∙∙ interaction are
responsible for the stability of the solid-state architecture of 4 (Fig. S6).
3.3 Electrochemical studies
The redox flexibility of the transition metal ion residing at the active site of
metalloenzyme plays vital role in the biocatalytic oxidation of various biologically important
organic compounds. Therefore, the electrochemical study of the enzymatic models could
disclose their ability of functioning biomimetic catalysis. In this regard, the electrochemical
properties of all complexes were examined in methanol in presence of 0.1 M
tetrabutylammonium perchlorate as a supporting electrolyte. Cyclic voltammograms of 1 − 3
are displayed in Fig. 6, while Fig. 7 shows the electrochemical behaviour of 4. Cyclic
16

voltammograms of 13 consist of an irreversible reduction response in the range –0.61 to –
1.01 V, which is associated with the reduction of cobalt(III) to cobalt (II) at the electrode
surface. The cyclic voltammogram of 4 also consists of a similar irreversible reductive
response at –0.77 V. Additionally, an irreversible oxidative response was observed in 4 at
0.96 V. The reduction process is as usual responsible for the reduction of cobalt (III) to cobalt
(II) of the complex cation at the electrode surface, while the oxidative response is due to the
oxidation of cobalt (II) to cobalt (III) of the complex anion of formula [Co(SCN)4]2–.
Fig. 6. Cyclic voltammograms of 1−3 in methanol at room temperature containing
tetrabutylammonium perchlorate as a supporting electrolyte at a scan rate 100 mV s‒1.
Fig. 7. Cyclic voltammogram of 4 in methanol at room temperature containing
tetrabutylammonium perchlorate as a supporting electrolyte at a scan rate 100 mV s‒1.
17

3.4 Catalytic oxidation of o-aminophenols
UV-vis spectrophotometric method was applied to study oxidation of o-aminophenol
(OAPH), by molecular dioxygen in presence of catalytic amount of the complexes in
dioxygen-saturated methanol at room temperature [33]. In this context, 5.0 ×10–5
M
methanolic solution of the complexes were allowed to react with a 1.0 ×10–2 M solution of
OAPH. The progress of the reaction was monitored UV–vis spectrophotometrically at a
regular time interval of 5 min, and the time-dependent spectral profiles for aerobic oxidation
of OAPH catalysed by 2 and 3 are depicted in Fig. 8, while Fig. S7 represents the oxidation
of OAPH by 1 and 4. These spectral scans show the cumulative growth of spectral band at ca.
434 nm, which indicate the accumulation of 2-aminophenoxazinone as a function of time
[61]. Careful inspection of these spectral scans at least qualitatively suggests that complex 2
and 3 are efficient catalysts for the oxidation of OAPH, while 1 and 4 are less reactive.
Furthermore, a blank test was performed under same experimental condition in absence of the
catalysts, where no such significant growth of spectral band is observed, supporting the role
of catalysts in such reaction. In order to inculcate the catalytic efficiency of these complexes
detailed kinetic study is performed in which 1.0×10–5 M solutions of the complexes were
reacted with excess substrate at the pseudo-first-order condition and initial rates were
evaluated. Plots of initial rate versus concentration of the substrate for oxidation of OAPH
catalyzed by 1−4 show a typical rate saturation kinetics (Fig 9, Fig. S8), indicating the course
of reaction proceeds through formation of a stable complex-substrate aggregate. These rate
saturation profiles can be analyzed applying the Michaelis–Menten model to evaluate kinetic
parameters Vmax, KM, and Kcat (Table 3). The turnover numbers (TON) of the catalysts were
then calculated by dividing the value of Vmax by the concentration of catalyst used and values
are found to be 3.79, 51.74, 48.40 and 11.84 h−1 for 14, respectively.
18

Literature data reveal that a fair number of model oxidations of o-aminophenol have
been carried out to mimic phenoxazinone synthase activity to gain insight into the possible
mechanism and to check efficiency of the synthetic analogues. In comparison to the literature
data, it is clear that although 1 and 4 are less reactive but 2 and 3 are efficient catalysts for
oxidation of o-aminophenol [45] The catalytic efficiency of the present compounds is slightly
higher than the reported analogous compounds by us [50]. In previous cases, ethoxy or
methoxy substitution at ortho position of the donor phenolate group of the Schiff base ligands
may increase the steric crowding around the coordination sphere of the metal centre, leading
to slightly weaker complex-substrate adduct formation ability, while in the present case no
such effect may be expected as Br is substituted at para position with respect to the donor
phenolate group. It is to be further noted that the catalytic oxidation of some substituted o-
aminophenols and isolations and characterizations of their oxidised products were conducted
with native enzyme and its models, but the detailed kinetic studies were not available in the
literature. Therefore, it could be worthy to carry out the detailed kinetic investigations with
some substituted o-aminophenols to get further insights into the reactive intermediates and
the mechanistic details of the catalytic reactions and finally to establish the structure-
reactivity correlation of the catalysts. Accordingly, the reaction kinetics of aerobic oxidation
of 2-amino-5-methylphenol catalysed by the most reactive compounds 2 and 3, leading to
production of 2-amino-4,4a-dihydro-4a-7-dimethyl-3H-phenoxazineone (Phx-2), was carried
out UV-vis spectrophotometrically (Fig. 10). Like o-aminophenol, the catalytic oxidation of
this substituted o-aminophenol proceeds through the formation of a stable catalyst-substrate
intermediate as suggested by the rate saturation kinetics (Fig 11) before the redox degradation
of the intermediate in the rate determining step. Detailed kinetic analysis further gives us
values of various kinetic parameters Vmax, KM, and Kcat which along with turnover numbers
are given in Table 3.
19

Fig. 8. UV-vis spectral profile for the aerobic oxidation of o-aminophenol (1.0 × 10−2 M)
catalysed by 2 and 3 (5.0 × 10−5 M) in methanol. The spectra were recorded at 5 min intervals
under aerobic conditions at room temperature
Fig. 9. Plots of initial rate versus substrate concentration for the aerobic oxidation of OAPH
in methanol catalysed by 1–4 at room temperature. Symbols and solid lines represent the
experimental and simulated profiles, respectively.
20

Fig. 10. Time dependent spectral scan showing growth of 4a,7-dimethyldihydro-2-
aminophenoxazinone at 405 nm upon addition of 2-amino-5-methylphenol to a solution
containing 2 or 3 in dioxygen-saturated methanol. The spectra were recorded at 5 min
intervals under aerobic conditions at room temperature
Fig. 11. Initial rate versus substrate concentration plot for the oxidation of 2-amino-5-
methylphenol in dioxygen-saturated methanol catalysed by 2 or 3 at room temperature.
Symbols and solid lines represent the experimental data and theoretical fit, respectively.
21

Table 3: Kinetic parameters of phenoxazinone synthase like activity for complexes 1–4.
Substrate
Catalyst
Vmax (Ms−1)
KM (M)
kcat (h−1)
3.79
(1.05 ± 0.06) × 10−8 (1.52 ± 0.15) × 10−2
(1.44 ± 0.04) × 10−7 (6.16 ± 0.43) × 10−3
1
2
3
4
2
3
51.74
48.40
11.84
88.01
64.14
OAPH
(1.34 ± 0.08) × 10−7
(8.95 ± 1.1) × 10−3
(3.29 ± 0.10) × 10−8 (6.39 ± 0.42) × 10−3
(2.44 ± 0.03) × 10−7 (2.59 ± 0.86) × 10−3
(1.78 ± 0.03) × 10−7 (2.69 ± 0.13) × 10−3
2-amino-5-
methylphenol
3.5 Proposed mechanism, comparative catalysis and mass spectrometry
Among the several factors that can affect the catalytic efficiency of the synthetic analogues,
the electronic environment around the metal centers and the labile position(s) at metal sites
for substrate binding are the most crucial factors behind their efficient activities. In present
systems, although the reduction potentials of the cobalt(III) centres are comparable, the
excellent catalytic activity of 2 and 3 over 1 and 4 is mainly due to the ease of formation of
stable complex-substrate intermediates by the replacement of labile sites (azide ions in 2 and
thiocyanate ions in 3) from the metal centres. Therefore, the course of catalytic reaction
proceeds through the inner sphere electron transfer pathway in 2 and 3, which is expected to
be quite faster than the outer sphere electron transfer pathway that follows when 1 and 4 are
used as catalysts where the metal centres are coordinatively saturated and no labile position is
available for substrate binding. However, the better lability of azide over thiocyanate ion is
responsible for somewhat greater reactivity of azide complex (2) compared to thiocyanate
analogue (3). From the kinetic data, it is also clear that the catalytic oxidation of methyl
substituted o-aminophenol is rather favourable than that of o-aminophenol itself which is
quite reasonable as the electron donating methyl substitution facilitates the oxidation process.
22

But it ultimately produces dihydro-aminophenoxazinone chromophore instead of
aminophenoxazinone chromophore as that methyl substitution blocks the final two-electrons
oxidation step (scheme 3).
The mass spectral study could provide valuable information regarding the product and
intermediate species that helps to establish the catalytic pathway of phenoxazinone synthase-
like activity. Accordingly, the electrospray ionization mass spectra of a reactive compound 3
in presence of 20 equivalents of o-aminophenol or 2-amino-5-methylphenol in methanol were
recorded and are displayed in Fig. 12 and 13, respectively. When o-aminophenol was used as
a substrate, the basal peak was found at m/z = 110.12, which is nothing but the protonated
species of substrate itself (calcd. m/z = 110.06), while for substrate 2-amino-5-methylphenol
the basal peak at m/z = 243.23 is matched with the protonated species of the product 3-
amino-1,4a-dihydro-4a-8-dimethyl-2H-phenoxazine-2-one (calcd. m/z = 243.11). Moreover,
a product related peak at m/z = 213.17 (calcd. m/z = 213.06), consisting of the protonated
species of the 2-aminophenoxazinone, is observed in the mass spectrum when o-aminophenol
was used as a substrate. Similarly, a peak at m/z = 124.14 (calcd. m/z = 124.08) related to
protonated species of substrate itself was found in the mass spectrum when 2-amino-5-
methylphenol was used as a substrate. In both cases, a common peak at m/z = 741.45 (calcd.
m/z = 741.19) is found in the mass spectra that indicates a species of composition
[(HL)2+H2O+K]+. The appearance of two other peaks at m/z 509.30 (calc. 509.10) for
substrate o-aminophenol and m/z 521.32 (calc. 521.10) for substrate 2-amino-5-methylphenol
are quite interesting as they support the formation of complex-substrate intermediate species
of
compositions
[(CoL)(OAPH)+H]+
and
[(CoL)(2-amino-5-methylphenolate)]+,
respectively. These observations clearly establish the ease of formation of stable complex-
substrate aggregates, exploiting the stronger chelating ability of o-aminophenolate ions by the
removal of terminal pseudohalide ions. The peak at m/z = 215.18 is also deserved to be
23

special mention as that is related to a monocationic species of an important reactive
intermediate II-B (calcd. m/z = 215.08) produced during the course of oxidative coupling of
o-aminophenol as drown in scheme 3.
We are now at the right position where both the mass spectral study and kinetic data
clearly suggest that the catalytic cycle for the aerobic oxidation of o-aminophenol catalysed
by 2 and 3 starts with the formation of a stable complex-substrate aggregate by the
substitution of two coordinated pseudohalides by o-aminophenolate ion. This complex-
substrate intermediate generates o-aminophenolate radical through the inner sphere electron
transfer from o-amionophenolate to the cobalt(III) centre in the rate determining step. Being
unstable the OAP radical thereafter is oxidised to o-benzoquinone monoamine (BQMI) in
several ways including disproportionation of the OAP radical itself. The intermediate
(BQMI) undergoes oxidative coupling with another molecule of OAP to produce a reactive
intermedia I-B, followed by two electrons oxidation with molecular oxygen to produce
another reactive intermediate II-B as supported by mass spectral study, which ultimately
gives final product 2-aminophenoxazinone through the oxidative dehydrogenation of
intermediate II-B as shown in Scheme 3. Similar mechanistic pathway is also applicable for
catalytic oxidation of 2-amino-5-methylphenol in which methyl substitution does not inhibit
the formation of a stable complex-substrate intermediate. Even that methyl substitution does
not inhibit the coupling of two aminophenols, but the final 2-electrons oxidation was blocked
by methyl substitution, leading to the formation of dihydro-phenoxazinone chromophore
instead of phenoxazinone chromophore as found for the oxidation of o-aminophenol itself
(see Scheme 3).
24

Fig. 12. Electrospray ionization mass spectrum (ESI-MS positive) of a 1:20 mixture of
complex 3 and o-aminophenol in methanol recorded after 10 min of mixing.
25

Fig. 13. Electrospray ionization mass spectrum (ESI-MS positive) of a 1:20 mixture of
complex 3 and 2-amino-5-methylphenol in methanol recorded after 10 min of mixing.
26

Scheme. 3. Proposed mechanistic pathway for the aerobic oxidation of o-aminophenols
catalysed by 2 and 3.
4. Conclusions
A new tetradentate N3O donor Schiff base ligand has been synthesized by the condensation
reaction of N,N-dimethyldipropylenetriamine and 5-bromosalicylaldehyde. This Schiff base
ligand was allowed to react with cobalt(II) ions in presence of different counter ions that
resulted diverse cobalt complexes where influence of both counter ions and the solvents on
27

structural diversity has been observed. All these complexes exhibit phenoxazinone synthase
mimicking activity, but the reactivity of 2 and 3 is significantly higher than that of 1 and 4.
The available labile sites for the substrate binding in 2 and 3 is the main reason behind the
stronger activity of 2 and 3 than the others. Literature reports reveal that although the
catalytic oxidation of some substituted o-aminophenols and isolations and characterizations
of their oxidised products were carried out with the native enzyme and its models, but the
detailed kinetic studies were not available in the literature. Herein, we have examined the
detailed kinetic studies of the aerobic oxidation of two substituted o-aminophenol, namely 2-
amino-5-methylphenol, using 2 and 3 as catalysts. The present results disclose that the
catalytic oxidation of methyl substituted o-aminophenols is much favourable than the
oxidation of o-aminophenol itself which is due to the electron donating effect of methyl
substitution, leading to the facile oxidation of these substrates. Interestingly, this methyl
substitution does not inhibit the formation of a stable complex-substrate intermediate in the
catalytic cycle and the oxidative coupling of two o-aminophenols as well, but the final two-
electrons oxidation step was blocked by methyl substitution, leading to the formation of
dihydro-phenoxazinone chromophore instead of phenoxazinone chromophore that observed
for oxidation of o-aminophenol itself. ESI mass spectral study provides significant
information from which the mechanistic pathway of functioning such catalytic activity has
been explored.
Acknowledgements
A. P. also gratefully acknowledges the financial support of this work by the University Grant
Commission, India (Sanction no. F. PSW-229/15-16(REO)). Panskura Banamali College
acknowledges the grants received from Department of Science and Technology (DST), Govt.
28

of India through FIST program (SR-FIST-Col/295 dated 18/11/2015). The authors thank
Jadavpur University, Kolkata for providing the Mass spectral facility.
Supplementary data
† Electronic supplementary information (ESI) available: The electronic supplementary
information file contains Figs. S1–S8. CCDC 1874230-1874233 contain the supplementary
crystallographic data for 1–4, respectively. For ESI and crystallographic data in CIF or other
electronic format see DOI: To be filled by the publisher.
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