Peroxidase activity of new mixed-valence cobalt complexes with ligands derived from pyridoxal

Article abstract of DOI:10.1002/aoc.4903

New mixed-valence cobalt complexes with ligands derived from pyridoxal were synthesized and characterized, and their application as mimetics of the peroxidase enzyme was investigated. Single-crystal X-ray diffraction was used to analyze all complex structures in the solid state and their electrochemical behavior was investigated. A reactivity pattern was observed in the complex synthesis regarding the cobalt compounds from which analogous zwitterionic derivatives were obtained. The importance of these compounds lies in understanding their behavior in an oxidizing environment and evaluating whether they can activate hydrogen peroxide to oxidize phenolic compounds. In nature, enzymes called peroxidases, which efficiently oxidize phenolic compounds, trigger many reactions involving the activation of hydrogen peroxide to oxidize organic substrates. However, these enzymes present several disadvantages, including denaturation and elevated costs. Therefore, these limitations can be overcome by expanding research into the study of synthetic catalysts for the oxidation of phenolic compounds using hydrogen peroxide, which is a highly relevant field of bioinorganic chemistry.

Full text of DOI:10.1002/aoc.4903

Received: 15 October 2018
DOI: 10.1002/aoc.4903
Revised: 26 December 2018
Accepted: 18 February 2019
F U L L P A P E R
Peroxidase activity of new mixed‐valence cobalt complexes
with ligands derived from pyridoxal
Liniquer André Fontana1 | Josiéli Demetrio Siqueira1 | Joice Ceolin1 |
Bernardo Almeida Iglesias2
| Paulo Cesar Piquini3 | Ademir Neves4 | Davi Fernando Back1
1 Laboratório de Materiais Inorgânicos –
Departamento de Química, CCNE, UFSM,
97105‐900 Santa Maria, RS, Brazil
2 Laboratório de Bioinorgânica e Materiais
Porfirínicos, CCNE, UFSM, 97105‐900
Santa Maria, RS, Brazil
New mixed‐valence cobalt complexes with ligands derived from pyridoxal were
synthesized and characterized, and their application as mimetics of the perox-
idase enzyme was investigated. Single‐crystal X‐ray diffraction was used to ana-
lyze all complex structures in the solid state and their electrochemical behavior
was investigated. A reactivity pattern was observed in the complex synthesis
regarding the cobalt compounds from which analogous zwitterionic derivatives
were obtained. The importance of these compounds lies in understanding
their behavior in an oxidizing environment and evaluating whether they can
activate hydrogen peroxide to oxidize phenolic compounds. In nature, enzymes
called peroxidases, which efficiently oxidize phenolic compounds, trigger many
reactions involving the activation of hydrogen peroxide to oxidize organic sub-
strates. However, these enzymes present several disadvantages, including dena-
turation and elevated costs. Therefore, these limitations can be overcome by
expanding research into the study of synthetic catalysts for the oxidation of
phenolic compounds using hydrogen peroxide, which is a highly relevant field
of bioinorganic chemistry.
3 Departamento de Fisica, CCNE, UFSM,
97105‐900 Santa Maria, RS, Brazil
4 Departamento de Química, Universidade
Federal de Santa Catarina, UFSC, 88040‐
970 Florianópolis, SC, Brazil
Correspondence
Davi Fernando Back, Laboratório de
Materiais Inorgânicos – Departamento de
Química, CCNE, UFSM, 97105‐900, Santa
Maria, RS, Brazil.
Email: davi.f.back@ufsm.br
Funding information
Brazilian Research Councils: CNPq,
Grant/Award Number: Proc. Num.
444780/2014‐9, 303011/2016‐5 and
424514; UFSM/CNPQ‐PIBIC, Grant/
Award Number: 2016 (043272).;
FAPERGS, Grant/Award Number: ED.
02/2017 ‐ PqG; UFSM/CNPQ‐PIBIC‐2016,
Grant/Award Number: 443625‐2014‐0
KEYWORDS
cobalt, peroxidase activity, pyridoxal, zwitterionic complexes
1 | INTRODUCTION
combinations of N, S, and O atoms (alcohol dehydroge-
nase),[9] which form the coordination sphere of the metal.
New polydentate ligands associated with N, O, and S atoms
have been attracting increasing interest in coordination
chemistry and associated areas (mainly bioinorganic
chemistry, catalysis, and material science).[1–3] In
bioinorganic chemistry, coordination complexes with
these ligands are widely studied as enzymatic
mimetics.[4–6] This is because the active sites of many
metalloenzymes exhibit nitrogen and sulfur (nitrile
hydratase),[7] nitrogen and oxygen (SOD‐Mn),[8] or even
Therefore, the present study aimed to explore ONS
Schiff base‐type ligands with nitrogen derived from an
azomethine group (imine), oxygen from a phenol group,
and sulfur from a thioether group. Schiff bases are versa-
tile ligands in coordination chemistry[10] that are easily
obtained by the reaction between a primary amine and
an aldehyde.
Pyridoxal was chosen for ligand synthesis due to its
rich coordination chemistry.[11] This aldehyde is a
Appl Organometal Chem. 2019;e4903.
wileyonlinelibrary.com/journal/aoc
© 2019 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.4903

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FONTANA ET AL.
derivative of vitamin B6 and the cofactor of several enzy-
matic reactions related to protein metabolism, especially
transamination, racemization, and decarboxylation of
amino acids.[11,12] Therefore, Schiff base‐type ligands
were obtained from the reaction of pyridoxal with 2‐
aminothiophenol derivatives.
32N system) at room temperature and under argon atmo-
sphere, in dry DMF solution. Electrochemical‐grade
tetrabutylammonium hexafluorophosphate (TBAPF6;
0.1 M) was used as supporting electrolyte. A standard
three‐component system was employed to carry out these
cyclic voltammetry experiments with a glassy carbon
working electrode, a platinum wire auxiliary electrode,
and a platinum wire pseudo‐reference electrode. To mon-
itor the reference electrode, the ferrocenium/ferrocene
redox couple was used as an internal reference.[22]
GC‐MS analyses were performed using a Shimadzu
QP2010PLUS GC‐MS combination (Shimadzu Instru-
ments). The GC was equipped with a low‐polarity (5%
phenylsiloxane, 95% methylsiloxane) capillary column
(30 m length, 0.25 mm inner diameter, 0.25 μm film
thickness). Samples were dissolved in ethyl acetate at a
concentration of 3 mg ml−1 and injected into the instru-
ment with an autosampler. The injector temperature
was maintained at 250°C and the transfer interface at
280°C. The oven temperature was ramped from 50 to
250°C at a rate of 15°C min−1. The QP2010PLUS is an
electron ionization quadrupole‐based mass spectrometer
with a maximum scan range of 900 amu and an ionizing
electron energy of 70 eV.
Cobalt complexes with Schiff bases, which can revers-
ibly bind to oxygen and carbon dioxide,[13] are a new
alternative for the catalytic activation of these substances.
In addition, they are efficient catalysts for the oxidation of
olefins and oxidative coupling of phenols[14] and aromatic
amines.[15–17] Therefore, the main interest in the com-
pounds synthesized in this study is their behavior in the
oxidizing environment and whether hydrogen peroxide
can be activated through the oxidation of phenolic com-
pounds and aromatic amines. In nature, many reactions
involving the activation of hydrogen peroxide for the oxida-
tion of organic substrates are triggered by enzymes called
peroxidases.[18–20] Despite the efficiency of these enzymes
in oxidizing phenolic or amine compounds, they present
some limitations, including denaturation and high costs.[21]
In order to overcome such restraints, synthetic cata-
lysts to oxidize phenolic and amine compounds using
hydrogen peroxide have become an exciting alternative.
This paper reports the synthesis and characterization
of a new series of zwitterionic cobalt complexes. The
structural and electronic properties of the compounds
were investigated using X‐ray diffraction, UV–visible
absorption spectroscopy, electrochemical analysis, and
measurements of peroxidase activity.
2.2 | X‐ray crystallography
Data were collected using a Bruker D8 Venture Photon
100 diffractometer equipped with an Incoatec IμS high
brilliance Mo Kα X‐ray tube with two‐dimensional Montel
micro‐focusing optics. The structure was solved by direct
methods using SHELXS.[23] Subsequent Fourier‐
difference map analyses yielded the positions of the non‐
hydrogen atoms. Refinements were carried out with the
SHELXL package.[23] All refinements were made by full‐
matrix least‐squares on F 2 with anisotropic displacement
parameters for all non‐hydrogen atoms. Hydrogen atoms
were included in the refinement in calculated positions
but the atoms (of hydrogen) that are involved in special
bond were located in the Fourier map. Visualization was
done using DIAMOND for Windows.[24] Crystal data
and more details of the data collection and refinements
of complexes ZW2C, ZW3C and ZW4C are presented in
Table 1.
2 | EXPERIMENTAL
2.1 | Materials and instrumentation
All manipulations were conducted by use of standard N2
atmosphere. CHN elemental analyses were performed
with a Shimadzu EA112 microanalysis instrument. 1H
NMR and 13C NMR spectra were recorded with a Bruker
DPX‐400 spectrometer. DMSO‐d6 and CDCl3 were used
as the solvent and tetramethylsilane as the internal
reference. Chemical shifts are reported in parts per
million (δ, ppm) and were referenced to residual solvent
peak. Multiplicities are expressed as: s, singlet; t, triplet;
q, quartet; quintet; sextet, m, multiplet; and br, broad.
Fourier transform infrared (FT‐IR) spectra were recorded
using a Bruker Tensor 27 spectrometer with KBr pellets
in the range 400–4000 cm−1. UV–visible absorption
2.3 | Peroxidase activity
2.3.1 | Phenol substrate
spectra were recorded with
spectrometer in dimethylformamide (DMF) solution.
Cyclic voltammograms were recorded with
potentiostat/galvanostat (AutoLab EcoChemie PGSTAT
a Shimadzu UV‐2600
Peroxidase activity was spectrophotometrically measured
by monitoring the absorbance relative to the adduct
phenol–(4‐aminoantipyrine) chromophore at 510 nm[25]
a

FONTANA ET AL.
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TABLE 1 Crystal data and structure refinement for ZW2C, ZW3C and ZW4C
ZW2C
ZW3C
ZW4C
Empirical formula
C32H34Cl3Co2N4O4S2
826.96
C36H41Cl3Co2N5O4S2
896.07
C40H45Cl3Co2N6O5S2
978.15
Formula weight
T (K)
100(2)
100(2)
100(2)
Radiation, λ (Å)
Mo Kα; 0.71073
Monoclinic, P21/c
10.8177(2)
20.2118(4)
16.9884(4)
90
Mo Kα; 0.71073
Monoclinic, P21/n
11.6726(19)
16.855(3)
Mo Kα; 0.71073
Monoclinic, C2/c
22.019(4)
Crystal system, space group
Unit cell dimensions a (Å)
b (Å)
14.120(3)
c (Å)
20.913(4)
29.062(6)
α (°)
90
90.00(3)
β (°)
91.6250(10)
90
101.585(6)
90
95.49(3)
γ (°)
90.00(3)
V (Å)
3712.94(13)
4, 1.479
4030.6(12)
4, 1.477
8994(3)
Z, calculated density (g cm−3
)
8,1.445
Absorption coefficient (mm−1
)
1.262
1.170
1.057
F (000)
1692
1844
4032
Crystal size (mm)
0.484 × 0.241 × 0.132
2.02–27.16
0.292 × 0.257 × 0.143
2.33–29.55
0.230 × 0.168 × 0.072
2.28–30.59
Theta range for data collection
Index ranges
−12 < =h < =13
−25 < =k < =25
−21 < =l < =21
−16 < =h < =13
−19 < =k < =23
−13 < =l < =28
−31 < =h < =31
−20 < =k < =19
−41 < =l < =33
Reflections collected/unique
Completeness to theta max.
Absorption correction
51780/8227
99.9%
18767/11260
99.8%
50093/13759
99.7%
Multi‐scan
0.9766 and 0.8859
Multi‐scan
0.800 and 0.862
Multi‐scan
0.801 and 0.862
Max. and min. transmission
Refinement method
Full‐matrix least‐
squares on F 2
Full‐matrix least‐squares
on F 2
Full‐matrix least‐
squares on F 2
Data/restraints/parameters
Goodness‐of‐fit on F 2
Final R indices [I > 2σ(I)]
R indices
8227/0/412
11260/0/470
13759/2/537
1.046
1.107
1.013
R1 = 0.0637, wR2 = 0.1839
R1 = 0.0837, wR2 = 0.1984
0.234 and −0.493
R1 = 0.0706, wR2 = 0.1442
R1 = 0.1841, wR2 = 0.1917
0.071 and −0.379
R1 = 0.0686, wR2 = 0.1985
R1 = 0.0965, wR2 = 0.2171
0.361 and −0.245
Largest diff. peak and hole (e Å−3
)
and 506 nm.[26] A modified methodology of Fontana and
co‐workers[27] (Scheme 1) was used. Phenol and 4‐
aminoantipyrine stock solutions were made by dissolving
the corresponding masses in a 1 mM phosphate buffer
solution (pH 7.0). Solutions of the 1.45 mM complexes
(and ligands) were made in DMF and calibrated spectro-
photometrically. The reactants were added to a quartz
cuvette in order for the concentration of the reactants at
the start of the reaction to be phenol 2.58 mM, 4‐
aminoantipyrine 1.05 mM, hydrogen peroxide 9.95 mM,
and complex (or ligand) 9.65 mM. The start of the
reaction was timed after the addition of hydrogen perox-
ide. The reaction was conducted at room temperature in
the absence of light. A blank experiment was performed
in the absence of catalyst (complex or ligand).
2.3.2 | 3,5,3′,5′‐Tetramethylbenzidine
(TMB) substrate
The substrate used for mimetic evaluation of peroxidase
was TMB, which generates the yellow‐colored oxidized

4 of 15
FONTANA ET AL.
2.3.3 | ortho‐Phenylenediamine (OPD)
substrate
OPD is a water‐soluble compound used as a substrate to
evaluate the mimetic peroxidase activity of cobalt com-
plexes. In contact with hydrogen peroxide and a catalyst,
this initial substrate produces an orange/yellow‐colored
product (formation of 2,3‐diaminophenazine (DAP) is
spectrophotometrically monitored at 450 nm).[17,31,32] To
obtain the buffer solution, 0.6 g of Na2HPO4 (anhydrous;
8.45 mM), 0.11 g of NaH2PO4·H2O (1.59 mM), and 4.3 g
of NaCl (0.15 M) were added to 500 ml of distilled water.
The OPD stock solution was prepared using 0.5 mg of the
compound in 1 ml of buffer solution and 10 μl of sulfuric
acid (2.0 M). For the hydrogen peroxide solution, 50 μL of
H2O2 was used in 5 ml of distilled water. The blank exper-
iment was performed in the absence of catalyst (complex or
ligand) with distilled water. The reagents were added to a
cuvette for the final concentrations of 3 ml of distilled
water, 0.92 mM OPD stock solution, 0.14 mM hydrogen
peroxide, and 3.78 mM catalyst (3.8 mM) (Scheme 3).
SCHEME 1 Schematic representation of stabilization of the
adduct 4‐aminoantipyrine–phenol. Scheme adapted from Kim and
collaborators[45]
TMB product (di‐iminic molecule) when in contact with
hydrogen peroxide and a catalyst. The absorbance was
spectrophotometrically monitored at 450 nm.[28–30]
The stock solution of TMB was prepared using 0.056 g
(2.3 mM) of TMB diluted in 2.5 ml of DMF and 2.5 ml
of acetic acid, followed by the addition of 50 μl of a KI
solution (5 mM). The hydrogen peroxide solution was
prepared using a concentration of 10 mM. The blank
experiment was run in the absence of a catalyst (complex
or ligand) with ethanol. The reagents were added to a
quartz cuvette at a final ratio of 3 ml ethanol, 50 μL
(0.77 mM) TMB stock solution, 50 μL (0.72 mM) hydro-
gen peroxide, and 30 μL (3.78 mM) of catalyst (Scheme 2).
SCHEME 3 Schematic representation of the diaminophenazine
obtained from the initial substrate OPD. Scheme adapted from the
literature[66,67]
SCHEME 2 Schematic representation
of stabilization of the diimine form of the
TMB substrate. Scheme adapted from the
literature[15,65]

FONTANA ET AL.
5 of 15
ν(C¼Car)]. 1H NMR (400 MHz, DMSO‐d6, δ in ppm):
0.86 (t, CH3, 3H), 1.37 (sextet, CH2, 2H), 1.52 (quintet,
CH2, 2H), 2.93 (t, CH2, 2H), 5.31 (br, C―NH3+, 3H),
7.24 (m, C―Har, 1H), 7.30 (m, C―Har, 1H), 7.45 (m,
C―Har, 1H), 7.53 (m, C―Har, 1H). 13C NMR (400 MHz,
DMSO‐d6, δ in ppm): 13.36 (CH3), 21.22 (CH2), 30.66
(CH2―CH2), 33.80 (CH2), 122.39 (Car), 126.54 (Car),
128.03 (Car), 128.06 (Car), 132.82 (Car), 135.15 (Car).
2.4 | Synthetic procedures
2.4.1 | Ligand synthesis: general
procedure
General
procedure
for
S‐alkylation
of
2‐aminothiophenol
2‐Aminothiophenol (0.250 g, 2.0 mmol) was dissolved in
anhydrous methanol (15 ml) and KOH (0.112 g,
2.0 mmol) was added. The bright yellow solution was
stirred during 30 min under N2 atmosphere. After this
period, a methanolic solution (10 ml) containing 2.0 mmol
of the corresponding alkyl halide (ethyl, propyl, or butyl)
was added dropwise, and the reaction mixture was stirred
at room temperature for 3 h. After this period, the meth-
anol was evaporated and the reaction extracted with
dichloromethane (3 × 25 ml). The dichloromethane was
evaporated, and the resulting oil was dissolved in metha-
nol (10 ml) and treated with concentrated hydrochloric
acid (to pH 2.0). The solvent was evaporated, and the
resulting solid was washed three times with diethyl ether
(15 ml). It was then recrystallized from methanol (20 ml)
to afford a white‐gray solid.
2.4.2 | General procedure for synthesis of
Schiff bases
General procedure for ligands L2C, L3C, and L4C
Pyridoxal hydrochloride (0.224 g, 1.1 mmol) was dis-
solved in anhydrous methanol (10 ml). Thereafter, the
respective amine (ethyl, propyl, or butyl) (0.189 g;
0.203 g; 0.217 g; 1 mmol each) was added and the mixture
was refluxed at 70°C for 2 h. After this period, the reac-
tion mixture was cooled to room temperature and KOH
(0.118 g, 2.1 mmol) dissolved in methanol (5 ml) was
added. The reaction was stirred at room temperature for
a further 15 min. The methanol was then evaporated
under reduced pressure and the solid washed three times
with water (15 ml), three times with ethyl ether (15 ml),
and three times with hexane (15 ml). The resulting solid
was filtered, recrystallized from methanol, and dried in
a desiccator (Scheme 4) and an orange crystalline sub-
stance was obtained.
Ligand L2C: 4‐(2‐(ethylthio)phenylimino)methyl‐5‐
(hydroxymethyl)‐2‐methylpyridin‐3‐ol. Yield: 87%. Anal.
Calcd for C16H18N2O2S (%): C 63.55; H 6.00; N 9.26.
Found (%): C 63.52; H 6.02; N 9.25. M.p. 133–134°C. FT‐
IR (KBr pellets, cm−1): 750 [m, ν(C―S)], 1605
[m, ν(C¼N)], 1581 [m, ν(C¼Car)], 1282 [f, ν(C―Oar)].
1H NMR (400 MHz, CDCl3, δ in ppm): 1,38 (t, CH3,
3H), 2,60 (s, CH3, 3H), 2,99 (q, S―CH2, 2H), 4,87 (s,
CH2―O, 2H), 7,24 (m, C―Har, 2H), 7,30 (m, C―Har,
1H), 7,37 (m, C―Har, 1H), 7,97 (s, C―Har, 1H) 9,16 (s,
C―Himine, 1H). UV–visible (DMF, λmax in nm; εmax in
M−1 cm−1): 276 (11 390). The X‐ray crystal structure
of the ligand is described in the supporting information.
2‐(Ethylthio)benzenamine hydrochloridrate. Yield:
68%. Anal. Calcd for C8H12NSCl (%): C 50.65; H 6.38;
N 7.38. Found (%): C 50.66; H 6.35; N 7.34. M.p. 157–
158°C. FT‐IR (KBr pellets, cm−1): 751.1 [m, ν(C―S)],
2846 [s, ν(C―NH3+)], 1507 [m, ν (C―NH3+)], 1558 [m,
ν(C¼Car)]. 1H NMR (400 MHz, DMSO‐d6, δ in ppm):
+
1.19 (t, CH3, 3H), 2.94 (q, CH2, 2H), 5.54 (br, C―NH3
,
3H), 7.21 (m, C―Har, 1H), 7.30 (m, C―Har, 1H), 7.44
(m, C―Har, 1H), 7.53 (m, C―Har, 1H). 13C NMR
(400 MHz, DMSO‐d6, δ in ppm): 14.59 (CH3), 28.90
(CH2), 122.51 (Car), 126.38 (Car), 127.44 (Car), 128.83
(Car), 133.86 (Car), 136.51 (Car).
2‐(Propylthio)benzenamine hydrochloridrate. Yield:
83%. Anal. Calcd for C9H15NSCl (%): C 53.06; H 6.93;
N 6.88. Found (%): C 53.00; H 6.92; N 6.82. M.p. 150–
153°C. FT‐IR (KBr pellets, cm−1): 748 [s, ν(C―S)], 2846
[s, ν(C―NH3+)], 1473 [m, ν(C―NH3+)], 1572 [m
ν(C¼Car)]. 1H NMR (400 MHz, DMSO‐d6, δ in ppm):
0.95 (t, CH3, 3H), 1.57 (sextet, CH2, 2H), 2.89 (t, CH2,
2H), 5.27 (br, C‐NH3+), 7.20 (m, C‐Har, 1H,), 7.28 (m,
C―Har, 1H), 7,42 (m, C―Har, 1H), 7,50 (m, C―Har,
1H). 13C NMR (400 MHz, DMSO‐d6, δ in ppm): 13.47
(CH3), 22.47 (CH3―CH2), 36.82 (S―CH2), 122.25 (Car),
126.32 (Car), 127.92 (Car), 128.52 (Car), 133.51 (Car),
136.30 (Car).
2‐(Butylthio)benzenamine hydrochloridrate. Yield:
94%. Anal. Calcd for C10H16NSCl (%): C 55.16; H 7.41;
N 6.43. Found (%): C 55.15; H 7.42; N 6.42. M.p. 141–
143°C. FT‐IR (KBr pellets, cm−1): 761 [m, ν(C―S)],
2854 [s, ν(C―NH3+)], 1473 [m, ν(C―NH3+)], 1557 [m,
SCHEME 4 Synthetic route of ligands L2C, L3C, and L4C
through condensation reaction of pyridoxal with 2‐
aminothiophenol derivative

6 of 15
FONTANA ET AL.
Ligand L3C: 4‐(2‐(propylthio)phenylimino)methyl‐5‐
6.77. Found (%): C 46.57; H 4.16; N 6.64. M.p. >350°C
(dec.). FT‐IR (KBr pellets, cm−1): 766.5 [m, ν(C―S)],
1604.3 [m, ν(C¼N)], 1573.7 [ν(C¼Car)], 1270 [m,
ν(C―Oar)]. UV–visible (DMF, λmax in nm; εmax in M
(hydroxymethyl)‐2‐methylpyridin‐3‐ol. Yield: 74%. Anal.
Calcd for C17H20N2O2S (%): C 64.53; H 6.37; N 9.26.
Found (%): C 64.58; H 6.44; N 8.77. M.p. 131–132°C. FT‐
IR (KBr pellets, cm−1): 754.4 [m, ν (C―S)], 1606.7 [m,
ν(C¼N)], 1582 [f, ν(C¼Car)], 1286 [m, ν(C―Oar)]. 1H
NMR (400 MHz, CDCl3, δ in ppm): 1.08 (t, CH3, 3H),
1.77 (sextet, CH2―CH2, 2H), 2.61 (s, CH3, 3H), 2.96
(t, CH2―S, 2H), 4.88 (s, O―CH2, 2H), 7.25 (m, C―Har,
2H), 7.31 (m, C―Har, 1H), 7.39 (m, C―Har, 1H), 7.93 (s,
C―Har, 1H), 9.19 (s, C―Himine,1H). UV–visible (DMF,
λmax in nm; εmax in M−1 cm−1): 276 (13 363).
−1
cm−1): 267 (50 144), 449 (11 143) and 490 (5571).
Complex ZW3C. Dark‐red crystals. Yield: 46%. Anal.
Calcd for C36H41N5O4S2Cl3Co2 (%): C 48.25; H 4.61; N
7.82. Found (%): C 48.57; H 4.66; N 7.54. M.p. >350°C
(dec.). FT‐IR (KBr pellets, cm−1): 765.7 [m, ν(C―S)],
1604.5 [m, ν(C¼N)], 1573.8 [ν(C¼Car)], 1271.5 [m,
ν(C―Oar)]. UV–visible (DMF, λmax in nm; εmax in M
−1
cm−1): 267 (66 092), 448 (14 687) and 489 (7343).
Ligand L4C: 4‐(2‐(butylthio)phenylimino)methyl‐5‐
(hydroxymethyl)‐2‐methylpyridin‐3‐ol. Yield: 63%. Anal.
Calcd for C18H22N2O2S (%): C 65.42; H 6.71; N 8.48.
Found (%): C 65.44; H 6.77; N 8.40. M.p. 124–125°C. FT‐
IR (KBr pellets, cm−1): 753.6 [m, ν(C―S)], 1607 [m,
Complex ZW4C. Dark‐red crystals. Yield: 63%. Anal.
Calcd for C40H45N6O5S2Cl3Co2 (%): C 48.86, H 5.13; N
8.55. Found (%): C 48.80; H 5.39; N 8.54. M.p. >350°C
(dec.). FT‐IR (KBr pellets, cm−1): 768.9 [m, ν(C―S)],
1602.8 [m, ν(C¼N)], 1573.5 [ν(C¼Car)], 1271.7 [m,
ν(C―Oar)]. UV–visible (DMF, λmax in nm; εmax in M
1
ν(C¼N)], 1582 [m, ν(C¼Car)], 1287 [m, ν(C―Oar)]. H
−1
NMR (400 MHz, CDCl3, δ in ppm): 0.96 (t, CH3, 3H),
1.52 (sextet, CH2―CH2―CH3, 2H), 1.72 (quintet,
S―CH2, 2H), 2.62 (s, CH3, 3H), 2.98 (t, CH2―S, 2H),
4.88 (s, O―CH2, 2H), 7.25 (m, C―Har, 2H), 7.31 (m,
C―Har, 1H), 7.40 (m, C―Har, 1H), 7.96 (s, C―Har, 1H),
9.18 (s, C―Himine, 1H). UV–visible (DMF, λmax in nm;
εmax in M−1 cm−1): 274 (16 769).
cm−1): 271 (42 323), 450 (9405) and 490 (4702).
2.5 | Computational details
Density functional theory was used to determine the Fukui
indices associated with the ZW2C, ZW3C, and ZW4C com-
plexes. Before calculating the Fukui indices, the molecular
structures of these three compounds were optimized, using
as starting configurations the X‐ray crystallographic data
for these compounds (see Section 4.1). The exchange and
correlation contributions were described by the hybrid
B3LYP functional. The molecular orbitals were represented
by linear combinations of relativistic effective‐core‐
potential double‐zeta quality basis sets.[33] All calculations
were done using the Gaussian 09 code.[34] The charge
density plots associated with the local Fukui functions were
obtained using the Chemcraft program.[35]
2.4.3 | Synthesis of complexes ZW2C,
ZW3C, and ZW4C
For the synthesis of these complexes, the reactions were
conducted in situ. In a round‐bottom flask containing
acetonitrile (20 ml) were added pyridoxal (0.20 mmol)
and the corresponding amine (0.20 mmol). The resulting
mixture was heated to 70°C and kept under magnetic stir-
ring for 30 min. After this period, upon the addition of
trimethylamine, an intense yellow coloration formed
which changed to dark brown upon addition of
CoCl2·6H2O (0.20 mmol). The resulting mixture was kept
under magnetic stirring for 3 h at 70°C. After the reac-
tion, the solution was filtered, and allowed to stand for
five days, with the slow evaporation of acetonitrile to
form dark‐red crystals (Scheme 5).
3 | RESULTS AND DISCUSSION
3.1 | Crystal structures of ZW2C, ZW3C,
and ZW4C
The three cobalt complexes synthesized have the same
coordination environments, which are usually octahe-
Complex ZW2C. Dark‐red crystals. Yield: 57%. Anal.
Calcd for C32H34N4O4S2Cl3Co2 (%): C 46.47; H 4.14; N
dral Co(III) coordinated to
O
(phenolate),
N
SCHEME 5 In situ synthetic route of
cobalt complexes ZW2C, ZW3C, and
ZW4C

FONTANA ET AL.
7 of 15
(azomethine), and S (thioether) atoms. On the other
hand, the Co(II) ion presents tetrahedral geometry coor-
dinating to the N (pyridine) from the pyridoxal and
three chlorides (Table 2 presents the principal bond
lengths and angles of the complexes). An ORTEP repre-
sentation of the structures of the three complexes is
shown in Figure 1.
Based on crystalline packing, it is possible to identify
centrosymmetric dimer formation in the structures of
complexes ZW2C and ZW3C (Figure 2). Each hydrogen
atom of each of the alcohol functions makes a strong
hydrogen bond[36,37] with a nitrogen atom of the
pyridine unit. The ZW2C complex forms two equivalent
hydrogen bonds with N (pyridinium)···H―O (alcohol)
bond distance equal to 2.799 Å. The ZW3C complex
forms an analogue dimer with N (pyridinium)···H―O
The octahedral cobalt ion has a coordination sphere
formed by two mono‐anionic ligands. Three anionic
chlorides and the pyridine nitrogen of one of the ligands
(pyridoxal derivative) coordinate to the tetrahedral
cobalt ion. Thus, considering the bonding distances
and strong tendency of Co(II) ions to adopt tetrahedral
geometry, it is possible to conclude that there is a neg-
ative charge on this atom due to the coordination of
three chlorine atoms. However, the octahedral cobalt
ion is Co(III) species, with a positive charge remaining
on this atom due to the coordination of only two
anionic ligands (phenolates). Thus, the complexes can
have a zwitterionic nature, with a negative charge on
the tetrahedral cobalt atom and a positive charge on
the octahedral cobalt atom, which makes the complex
neutral. Lengths and angles for the X‐ray structural
parameter analysis of complexes ZW2C, ZW3C, and
ZW4C are presented in Table 3.
(alcohol) and bond distance equal to 2.796
Å
(Table 4).
The other oxygen atom of the alcohol function (O4) of
the pyridoxal makes hydrogen bonds with electronegative
atoms (three chloride ions) coordinated to the Co(II) ions
(Figure 3).
3.2 | UV–visible absorption analysis
The absorption spectra of the ligands are shown in the
supporting information. The bands are observed around
276 and 364 nm, which can be attributed to the
intraligand transition bands π → π* and n → π*, respec-
tively.[38–41] Electronic transition bands between 400 and
550 nm are observed for cobalt complexes ZW2C,
ZW3C, and ZW4C, which can be attributed to ligand‐
to‐metal charge transfer transitions that involve the oxy-
gen of the phenolate (PhO− → Co(III))[42] (Figure 4;
Table 5). A low‐intensity band (shoulder) was observed
in the region between 600 and 700 nm, which may be
attributable to a d–d type transition.[43] The fact that
these Co complexes present Co(II) ions in a tetrahedral
environment suggests that lower energy transitions
probably occur based on Laporte/spin rules. Another
plausible explanation is that the solvent (DMF) may
coordinate with tetrahedral Co(II) species and change
its coordination geometry, possibly to an octahedral
environment.
TABLE 2 Distances for CoIII–N (imine), CoIII–O (phenolate),
CoIII–S (thiolate), CoIII–S (thioether), CoIII–S (thiolate)μ, CoII–Cl
and CoII–N (pyridine) and their respective references
Metal and Lewis Base
Bond (Å)
Ref.
[32]
CoIII–N (imine)
1.946(3)
2.046(3)
1.913(3)
1.926(2)
1.93
[60]
[61]
[62]
[63]
1.858 (7)
1.923(5)
[60]
CoIII–O (phenolate)
1.894(2)
1.914(2)
1.93
[61]
[63]
3.3 | Density functional theory results
1.898(5)
[32]
CoIII–S (thiolate)
CoIII–S (thioether)
2.217(3)
1.927(3)
2.227
To better understand the electronic nature of the zwitter-
ionic cobalt complexes, the Fukui functions have been
determined associated with electronic densities according
to the following equations:
[60]
[32]
2.2017(16)
2.221(3)
2.238
[60]
[63]
F þ ðrÞ ¼ ρNþ1ðrÞ − ρNðrÞ
2.196(2)
[62]
[61]
CoIII–S (thiolate)μ
2.3156
2.28
F − ðrÞ ¼ ρNðrÞ − ρN−1ðrÞ
[63]
[64]
CoII–Cl
CoII–N (piridine)
2.227(2)
where F+ and F − are the Fukui functions for the elec-
trophilic and nucleophilic regions of these complexes,
the electronic charge for a molecule with X electrons.
2.126(4)
2.138(4)

8 of 15
FONTANA ET AL.
FIGURE 1 Structural representation of complexes ZW2C, ZW3C, and ZW4C with 50% ellipsoids. Hydrogen atoms and crystallization
solvates are omitted for better visualization of the structure
TABLE 3 Bond lengths and angles for complexes ZW2C, ZW3C, and ZW4C
Bond length (Å)
ZW2C
Angle (°)
ZW2C
Atoms
ZW3C
ZW4C
Atoms
ZW3C
ZW4C
Co1–O3
Co1–O1
Co1–N4
Co1–N2
Co1–S1
Co1–S2
Co2–Cl1
Co2–Cl2
Co2–Cl3
Co2–N1
Co2–N3
1.879(3)
1.880(3)
1.874(3)
O3–Co1–O1
O3–Co1–N4
O1–Co1–N4
O3–Co1–N2
O1–Co1–N2
N4–Co1–N2
O3–Co1–S1
O1–Co1–S1
N4–Co1–S1
N2–Co1–S1
O3–Co1–S2
O1–Co1–S2
88.48(12)
92.53(14)
88.80(13)
89.49(13)
92.55(13)
177.60(13)
91.69(10)
179.29(10)
91.88(11)
86.76(10)
178.29(10)
91.52(9)
88.15(15)
93.78(15)
89.19(17)
86.63(16)
93.30(18)
177.49(18)
92.67(11)
179.17(12)
90.68(12)
86.83(14)
178.58(13)
90.65(12)
90.14(14)
92.43(14)
87.08(15)
86.40(14)
92.77(16)
178.82(15)
91.93(10)
177.90(10)
93.18(11)
87.01(12)
176.42(10)
93.43(11)
1.890(3)
1.884(3)
1.882(3)
1.907(3)
1.916(4)
1.923(3)
1.926(3)
1.932(5)
1.918(4)
2.2603(12)
2.2718(13)
2.2419(16)
2.2603(14)
2.2758(16)
2.078(3)
2.2623(15)
2.2647(16)
2.248(2)
2.2540(12)
2.2478(12)
2.2551(14)
2.2718(14)
2.2541(13)
2.2696(17)
2.2767(17)
─
─
─
2.070(4)
2.066(3)
N4–Co1–S2
N2–Co1–S2
85.77(11)
92.21(10)
86.97(12)
92.67(12)
88.02(11)
93.16(11)
S1–Co1–S2
88.33(5)
88.52(7)
84.50(5)
Cl1–Co2–Cl2
Cl1–Co2–Cl3
Cl2–Co2–Cl3
N1–Co2–Cl1
N1–Co2–Cl2
N1–Co2–Cl3
N3–Co2–Cl1
N3–Co2–Cl2
N3–Co2–Cl3
114.96(6)
110.22(7)
109.10(6)
105.48(11)
110.93(10)
105.74(11)
110.13(7)
109.73(6)
111.04(8)
112.36(5)
113.53(5)
109.03(5)
─
─
─
─
─
─
─
104.82(14)
107.84(13)
113.10(12)
104.93(10)
111.10(11)
105.65(11)
─
─

FONTANA ET AL.
9 of 15
FIGURE 2 Hydrogen bonds of complex
ZW2C at the crystallographic plane ac.
The crystallization solvates and hydrogens
not involved in the hydrogen bonds are
omitted
TABLE 4 Lengths and angles of hydrogen bonds characterized as strong according to the adopted parameters[36,37]
(D–H···A)
D–H (Å)
H···A (Å)
D···A (Å)
D–H···A (°)
ZW2C O–H...N
ZW3C O–H...N
0.820(5)
0.820(5)
2.136(5)
2.016(5)
2.799(6)
2.796(8)
137.91(26)
158.53 (32)
FIGURE 4 UV–visible absorption spectra of cobalt complexes
ZW2C, ZW3C, and ZW4C in DMF solution (10−5 M)
The electronic charge densities for the positive and
negative specimens of these three complexes, ρN‐1(r) and
FIGURE 3 Hydrogen bonds in complex ZW2C along the
direction [010]. The crystallization solvates and hydrogen atoms
not involved in the hydrogen bonds are omitted
ρN+1(r) respectively, have been determined through static
self‐consistent field electronic structure calculations using

10 of 15
FONTANA ET AL.
TABLE 5 UV–visible transition band data of free ligands (L2C,
L3C, L4C) and Co complexes (ZW2C, ZW3C, ZW4C)
peripheral tetrahedral Co(II) units, which corroborates
and give theoretical support to the experimental
evidences.
Compound
nm (ε, M−1 cm−1
)
L2C
276 (11 390)
276 (13 363)
274 (16 769)
L3C
3.4 | Cyclic voltammetry analysis
L4C
The electrochemical behavior of the Co complexes was
investigated using cyclic voltammetry with a platinum
electrode (working electrode) in a dry DMF solution in
the range 1.0 to 2.0 mM and with 0.1 M TBAPF6 as the
supporting electrolyte. This was performed in an argon‐
saturated atmosphere in the potential range −2.00 to
+1.50 V versus NHE (Figure 6; Table 6). In general, the
ligands presented an irreversible oxidation process in
the anodic region. This can be attributed to the oxidation
of the sulfur atom, which likely forms sulfoxide (SO) spe-
cies in solution. In the negative region, only one reduc-
tion process was observed, which can be assigned to the
imine group.[44]
For the complexes, zwitterionic cobalt species present
two reduction processes in the cathodic region. The first
reduction can be attributed to the CoIII/CoII reduction
process of the octahedral center,[42,45] leading to the sec-
ond process, which can be assigned to the ligand reduc-
tion process. In the positive region, all complexes
presented an irreversible anodic peak, which can be
attributed to the oxidation of tetrahedral Co(II) units,
forming the CoII/CoIII redox couple.[46] Additionally, oxi-
dation and reduction processes of cobalt ion revealed that
the redox behavior of zwitterionic Schiff base complexes
involves one‐electron transfer reaction each (confirmed
by coulometric analysis; see supporting information).
ZW2C
ZW3C
ZW4C
267 (50 144), 449 (11 143) and 490 (5571)
268 (66 092), 448 (14 687) and 489 (7343)
271 (2323), 450 (9405) and 490 (4702)
the same minimum energy configurations obtained for
the systems with N electrons.
The chemically active regions of these are qualitatively
described by the nucleophilic property, F −(r), Fukui
functions. The nucleophilic regions for the ZW2C,
ZW3C, and ZW4C complexes are presented in Figure 9.
From Figure 5, it can be clearly seen that the Co(II)
sites will always behave as nucleophilic active regions,
irrespective of the considered complex. On the other
hand, the Co(III) centers exhibit different nucleophilic
activities. For example, for the ZW3C molecule, the
Fukui function of Co(III) species shows no activity. Fur-
ther, in ZW4C complex, Co(II) units are seen to have a
greater nucleophilic activity among the three complexes.
Finally, the Fukui function by theoretical calculation
analysis suggests that the Co(III) ions show some nucleo-
philic activity in the ZW2C complex, although less than
in complex ZW4C. These qualitative results indicate that
the ZW4C cobalt derivative will show a stronger nucleo-
philic activity, when compared to the ZW2C and ZW3C
complexes, due to the greater chemical reactivity of the
FIGURE 5 Nucleophilic Fukui
functions for cobalt complexes (a) ZW2C,
(b) ZW3C, and (c) ZW4C. The figures
shown in (a–c) have been obtained using
the same isosurface value of 0.04 e A−3

FONTANA ET AL.
11 of 15
FIGURE 6 Cyclic voltammetry of dinuclear cobalt complexes
ZW2C, ZW3C, and ZW4C using 0.1 M TBAPF6 as support
electrolyte and scan rate of 50 mV s−1
FIGURE 7 Absorbance graphs for the reaction phenol + 4‐
aminoantipyrine + hydrogen peroxide + catalyst after 900 min of
reaction
TABLE 6 Summary of redox potential of free ligands and zwit-
terionic Co complexes
phenol–4‐aminoantipyrine chromophore formed was
very similar to the blank.
The results obtained using cobalt complexes were sim-
ilar to those reported by Kim and co‐workers,[47] who
used copper(II) perchlorate hexahydrate as a catalyst.
On the other hand, when comparing the results obtained
with those reported by Xiong and collaborators,[48] the
mixed‐valence complexes did not have the same effi-
ciency in aminontipyrine–phenol adduct formation.
Moreover, it is possible that the reaction mechanism
depends on the formation of peroxide bonds with the cat-
ion, which is disadvantageous in complexes with octahe-
dral coordination geometry, in addition to external sphere
mechanisms not being effective for these types of reac-
tions. The higher the absorbance value, the more effective
is the complex as a catalyst.
The concept of enzymatic mimetic activities is related
to the synthesis of molecules that simulate the active
site of an enzyme. Moreover, it is worth noting that this
concept is not inflexible. Thus, several articles in the
literature have reported reactions similar to those of
peroxidase, which use transition metal complexes
different from those of natural enzymes (when compar-
ing with data from horseradish peroxidase), such as
nickel,[27,49] cobalt,[21] and copper,[47] as well as non‐
porphyrinic ligands.
Compound
E1 (V)
E2 (V)
E3 (V)
L2C
+0.606a
+0.632a
+0.648a
+0.505a
+0.437a
+0.483a
−0.868b
−0.819b
−0.952b
−0.554a
−0.276a
−0.189a
—
L3C
—
L4C
—
ZW2C
ZW3C
ZW4C
−1.136b
−0.902b
−1.161b
aEpa = anodic peak.
bEpc = cathodic peak.
4 | PEROXIDASE MIMETIC ASSAYS
4.1 | Phenol substrate
Complexes and ligands were investigated for their ability
to activate hydrogen peroxide for phenol oxidation. Thus,
the reaction between phenol and 4‐aminoantipyrine was
monitored spectrophotometrically at 505 nm in order to
quantify the formation of phenol–(4‐aminoantipyrine)
chromophore (confirmed by GC‐MS analyses; see
supporting information). The absorption plots in the
region 400 to 700 nm obtained after 15 h of reaction are
shown in Figure 7. These results allowed us to draw a
general profile of the peroxidase activity of the com-
pounds synthesized in this study and correlate it with
the structure of the complexes obtained.
However, there are few reports in the literature of
mixed‐valence complexes with the pro‐oxidant activity
evaluated in this work. In one of these cases, Horn et al.
synthesized mixed‐valence manganese(III and IV) com-
plexes that were tested as possible peroxidase mimetics;
however, the complexes presented more significant
results for biomimetics of catalase activity.[50]
Ligands (L2C, L3C, and L4C) had no peroxidase
activity. This is because the amount of the

12 of 15
FONTANA ET AL.
be achieved by means of nanoparticulate materials, spe-
cifically Co2O3. By comparing the results to those of this
article, similar pro‐oxidant activity was observed; how-
ever, an advantage of the materials synthesized by Wang
et al. was the time/activity ratio in which constant
increases in the substrate conversion occurred.
Moreover, when the absorbance values for the oxida-
tion of the OPD substrate, which generates 2,3‐
diaminophenazine (Figure 9), are correlated with those
of Guan and co‐workers,[52] it is possible to observe that
the zwitterionic complex containing a four‐carbon‐atom
chain (ZW4C) also presented the best oxidation results
(confirmed by GC‐MS analyses; see supporting
information).
All complexes exhibit Co(III)/Co(II) reduction and
Co(II)/Co(III) re‐oxidation processes, that is, each com-
plex reduces, although it is regenerated after electrochem-
ical oxidation. The redox potential values for the cobalt
complexes in this study were observed between −0.18
and −0.55 V versus NHE. When compared with the
values found for the reduction of the native enzyme
horseradish peroxidase (E = −0.306 V versus NHE) in
the literature, the zwitterionic cobalt complexes have
reduction processes similar to the native enzyme (only
in terms of oxidation potential, as the activity itself is still
lower). This indicates that they may present activity
similar to that of the peroxidase of this plant
(horseradish).[53]
Activation of hydrogen peroxide catalyzed by cobalt
complexes is often associated with the formation of reac-
tive oxygen species such as superoxide radicals, hydroxyl,
and hydroperoxide.[54–57] These species are versatile oxi-
dants for various organic substrates; however, due to their
radical nature and consequently high reactivity, they
4.2 | Aromatic amine substrate
The readings were conducted at five‐minute intervals. A
graph was plotted after 2 h to relate the absorbance vari-
ation as a function of the time that the samples were irra-
diated in the spectrophotometer (wavelength of 450 nm).
As the oxidation of the initial substrates occurred, absor-
bance increased, that is, both the formation of TMB
diimine and the coupling reaction generated 2,3‐
diaminophenazine (confirmed by GC‐MS analyses; see
supporting information).
The isolated ligands do not have mimetic activity
because the absorbance values are closer to those
obtained in the reaction without a catalyst (blank). In this
sense, it is evident that the presence of labile ligands in
the coordination sphere of the Co(II) ions is crucial for
the activity of the complexes. However, the increase in
the organic chain of the organic ligand generated a more
positive potential reduction pattern, allowing higher reac-
tivity with hydrogen peroxide. Notably, the three com-
pounds evaluated in this study have similar molecular
structures and solvates.
By comparing the data with TMB oxidation, no equi-
librium between the radical formation of the charge
transfer complex was observed, providing a strong blue
coloration despite the diimine generated by the com-
plete oxidation of the TMB substrate (Figure 8). The
results found in the literature[15,30] illustrate the same
total oxidation mechanism, although with different
compounds.
Although not presenting zwitterionic characteristics,
an expressive example of peroxidase activity reported in
the literature was developed by Wang et al.,[51] who
showed that the activation of hydrogen peroxide can also
FIGURE 8 Absorbance plot (450 nn) in relation to time of
mixed‐valence Co complexes
FIGURE 9 Absorbance plot (450 nm) in relation to time of Co
complexes with mixed valence

FONTANA ET AL.
13 of 15
must be generated in the reaction medium itself. The
cobalt dinuclear complexes developed in this work have
different coordination environments and oxidation states,
one of which is octahedral Co(III) and the other tetrahe-
dral Co(II). In these complexes, the Co(II) atom is less
protected by the ligands when compared to the Co(III)
atom, and therefore it must be the main reactive site
(which is also corroborated by density functional theory
calculations), effectively interacting with hydrogen perox-
ide and promoting its activation. Thus, by assuming
that the Co(II) site is catalytic, it is plausible to believe
that the same reactional behavior described by Lázaro‐
Martínez[54] and Liang[55] can occur in the three com-
plexes investigated in this work.
SUPPLEMENTARY DATA
CCDC 1833006, 1833011, 1833139, and 1835012 contain
the supplementary crystallographic data for complexes
ZW2C, ZW3C and ZW4C and ligand L2C (supporting
information), respectively. These data can be obtained free
of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.
html, or from the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax:
(+44) 1223 336 033; or e‐mail: deposit@ccdc.cam.ac.uk.
ORCID
Bernardo Almeida Iglesias
4039-6316
https://orcid.org/0000-0002-
Davi Fernando Back
1503
https://orcid.org/0000-0002-9107-
5 | CONCLUSIONS
REFERENCES
Due to the coordination formed by a ligand containing
oxygen, nitrogen, and sulfur atoms, based on pro‐
oxidant activity observed in experiments, we believe that
peripheral Co(II) moiety may be related to peroxidase
activity. However, the three complexes present similar
coordination spheres, thus little difference was observed
in stereochemical reactivity. The main difference was
revealed by the cyclic voltammetry analysis of the com-
plexes, in which the complex ZW4C exhibited more pro-
nounced changes in regions of higher positive potential,
thus indicating the possible existence of (in situ) CoIII
ions.[58,59]
Therefore, we attribute the best peroxide activation
behavior to the complex with more reversible redox pro-
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sulfur‐ligand butyl substituent. Along with these observa-
tions, density functional theory calculations showed that
there is corroboration between metallic atoms, that is, a
higher nucleophilic activity in the two metallic centers,
a situation which was not evidenced in the other two
complexes. Reports of pro‐oxidant activities of zwitter-
ionic complexes are scarce; therefore, the results of this
work are innovative.
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How to cite this article: Fontana LA, Siqueira
JD, Ceolin J, et al. Peroxidase activity of new
mixed‐valence cobalt complexes with ligands
derived from pyridoxal. Appl Organometal Chem.
2019;e4903. https://doi.org/10.1002/aoc.4903
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