Co(III) N,N′-diarylformamidine dithiocarbamate complexes: Synthesis, characterization, crystal structures and biological studies

Article abstract of DOI:10.1002/aoc.5610

Three symmetric N,N-diarylformamidine dithiocarbamates, N,N′-bis(2,6-dimethylphenyl)formamidine dithiocarbamate (DTL1), N,N′-bis(2,6-disopropylphenyl)formamidine dithiocarbamate (DTL2) and N,N′-dimesitylformamidine dithiocarbamate (DTL3), and three unsymm

Full text of DOI:10.1002/aoc.5610

Received: 23 May 2019
DOI: 10.1002/aoc.5610
Revised: 17 January 2020
Accepted: 22 January 2020
F U L L P A P E R
Co(III) N,N0-diarylformamidine dithiocarbamate complexes:
Synthesis, characterization, crystal structures and biological
studies
Segun D. Oladipo1
| Bernard Omondi2
| Chunderika Mocktar3
1School of Chemistry and Physics,
Westville Campus, University of Kwazulu-
Natal, Private Bag X54001, Durban, 4000,
South Africa
2School of Chemistry and Physics,
Pietermaritzburg Campus, University of
Kwazulu-Natal, Private Bag X01,
Scottsville, 3209, South Africa
3Discipline of Pharmaceutical Sciences,
School of Health Sciences, University of
Kwazulu-Natal, Private Bag X54001,
Durban, 4000, South Africa
Three
bis(2,6-dimethylphenyl)formamidine dithiocarbamate (DTL1), N,N0-bis(2,6--
disopropylphenyl)formamidine dithiocarbamate (DTL2) and
N,N0-
symmetric
N,N-diarylformamidine
dithiocarbamates,
N,N0-
dimesitylformamidine dithiocarbamate (DTL3), and three unsymmetric ones,
N0-(2,6-dichlorophenyl-N-(2,6-dimethylphenyl)formamidine dithiocarbamate
(DTL4), N0-(2,6-dichlorophenyl)-N-(2,6-diisopropylphenyl)formamidine dithio-
carbamate (DTL5) and N0-(2,6-dichlorophenyl)-N-mesitylformamidine dithio-
carbamate (DLT6), were reacted with chloridocobalt(III) in water to give Co-
(DTL1)3 (1), Co-(DTL2)3 (2), Co-(DTL3)3 (3), Co-(DTL4)3 (4), Co-(DTL5)3 (5)
and Co-(DTL6)3 (6). All the dithiocarbamates and complexes were character-
Correspondence
1
ized using H NMR, 13C NMR, Fourier transform infrared, UV–visible and
Bernard Omondi, School of Chemistry
and Physics, Pietermaritzburg Campus,
University of Kwazulu-Natal, Private Bag
X01, Scottsville, 3209, South Africa.
Email: owaga@ukzn.ac.za
mass spectra and the purity confirmed by elemental analysis. In addition,
crystal structures of complexes 1, 2, 4 and 5 were determined, confirming the
formation of mononuclear species in which the Co(III) centers coordinated to
six sulfur atoms from three dithiocarbamate ligands resulting in distorted
octahedral geometries. All complexes showed moderate to good antibacterial
activities against Gram-negative bacteria Escherichia coli, Salmonella typ-
himurium, Klebsiella pneumoniae and Pseudomonas aeruginosa even at low
concentrations. None of the six were active against Gram-positive bacterium
methicillin-resistant Staphylococcus aureus and only active against S. aureus
at high concentrations. Complexes 5 and 6 were found to be more active than
ciprofloxacin against S. typhimurium, E. coli, P. aeruginosa and
K. pneumoniae and complexes with chloro-substituted ligands generally had
enhanced activities. Antioxidant activities of the dithiocarbamate salts and
their Co(III) complexes were also investigated using DPPH assay and the
complexes were found to be more efficient. Complex 2 with an IC50 value of
2.84 × 10−4 mM displayed the highest activity of all compounds tested, even
outdoing ascorbic acid. The radical scavenging ability of the complexes
followed the order 2 > 1 > ascorbic acid >3 > 4 > 6 > 5.
K E Y W O R D S
antioxidant, cobalt(III) complexes, dithiocarbamate, in vitro antibacterial activity, N,N0-
diarylformamidine
Appl Organometal Chem. 2020;e5610.
wileyonlinelibrary.com/journal/aoc
© 2020 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.5610

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OLADIPO ET AL.
1 | INTRODUCTION
antifungal,[26,29,30] antioxidant[31–33] and anticancer[34–36]
agents. Onwudiwe and Ekennia[25] reported in vitro anti-
microbial studies of N-ethyl-N-phenyldithiocarbamate
transition metal complexes and their research showed
that the antimicrobial activity of the free ligand
was enhanced upon chelation with metal ions. Their
study showed that the cobalt complex had better
antibacterial activity compared to streptomycin (stan-
dard) against S. aureus. Verma and Singh[37] also used a
multifunctional secondary amine ligand, 2-chloro-
In recent years, there has been an increase in the search
for new antimicrobial agents. The search is for agents
with better activity and potency, less toxicity and interest-
ing mechanisms of action.[1] This is due to the resistance
of existing microbes
t the available antimicrobial
agents.[2] In addition, there is the ever rapid surfacing of
new infectious diseases caused by various pathogenic
bacteria and viruses, which exacerbates the fight against
microbial resistance.[3] In trying to combat the two issues,
metal-based antimicrobial agents are increasingly gaining
prominence[3–5] and this has seen a variety of classes of
ligands and their transition metals being investigated.
An interesting aspect of studies of microbial agents is
that of combinatorial drugs that serve more than one
purpose. For example, drugs used in the prevention of
transmission of HIV-1 in women while simultaneously
averting unintended pregnancies are known and technol-
ogies that help in such efforts are established.[6,7] In the
same light, compounds with antioxidant properties have
been shown to be useful for slowing down the aging pro-
cess, in preventing food decay[8] and in the cosmetic and
pharmaceutical industries.[9,10] Free radicals generated
during normal metabolism in small quantities are impor-
tant to normal physiological function but can also pose a
danger to the body system when in excess. This leads to
damage of DNA, proteins and enzymes, resulting in high
risk of diseases such as Parkinson's disease, Alzheimer's
disease, asthma, angiocardiopathy and diabetes.[11] To
counterbalance the excess radicals produced in our bod-
ies, antioxidants such as ascorbic acid, α-tocopherol and
glutathione are often used.[12]
3{2-(piperazinyl)ethyl}amino-1,4-naphthoquinone,
to
synthesize mononuclear dithiocarbamate metal com-
plexes and screened them for in vitro antimicrobial activi-
ties. Their results showed that all complexes displayed
moderate to good antibacterial activities. In view of the
search for new compounds with excellent antibacterial
and antioxidant properties, herein we report the synthe-
sis, characterization, crystal structures and biological
properties (antibacterial and antioxidant) of novel
cobalt(III) dithiocarbamate complexes using symmetric
and unsymmetric formamidine as secondary amine.
2 | EXPERIMENTAL
2.1 | Materials
All solvents (ACS reagent grades, ≥99.5%) were obtained
from Sigma-Aldrich and used as obtained without further
purification. Reagents 2,6-diisopropylaniline (97%),
2,6-dimethylaniline (99%), 2,4,6-trimethylaniline (98%),
2,6-dichloroaniline (98%), triethyl orthoformate (99%)
and carbon disulfide were also obtained from Sigma-
Aldrich. CoCl2 (98%) and KOH (85%) were obtained from
Promark Chemicals, South Africa.
Dithiocarbamates and their metal complexes have
been reported to have useful antimicrobial and antioxi-
dant activity.[13] Dithiocarbamates themselves have
proved to be useful ligands in the field of coordination
chemistry.[13–15] Their synthesis is simple and inexpen-
sive and generally involves the reaction of either second-
ary or primary amines with carbon disulfides in the
presence of a base such as sodium hydroxide.[16,17] They
boast the ability to stabilize transition metals in various
oxidation states[14] and, in the process, to form complexes
with transition and main group metals.[18–20] Our interest
stems from the fact that properties and structural archi-
tectures of the eventual metal complexes can be tailored
by varying the substituents on the ligands bearing sec-
ondary or primary amines.[21]
2.2 | Instrumentation
1H NMR and C NMR spectra were recorded at 25 C
13
ꢀ
with Bruker Avance III 400 MHz and 600 MHz spectrom-
1
eters. Both H NMR and 13C NMR data were recorded in
either CDCl3 and referenced to the residual CDCl3 peaks
at 7.26 and 77.00 ppm or (CD3)2SO (DMSO-d6) and
referenced to the residual (CD3)2SO peaks at 2.50 and
39 ppm, respectively. Elemental analyses were recorded
with a Vario elemental EL cube CHNS analyzer. Infrared
(IR) spectra were obtained with a PerkinElmer Universal
ATR spectrum 100 FTIR spectrometer, UV–visible
absorption spectra were recorded with a Shimadzu UV–
Vis–NIR spectrophotometer and mass spectra of com-
Cobalt(III) dithiocarbamate complexes are of interest
for their application as catalysts,[22] single-source precur-
sors to prepare cobalt sulfide nanoparticles[21,23] and also
biologically active compounds.[24] Biologically, cobalt
complexes have been used as antibacterial,[25–28]
plexes were obtained using
a Water Synapt GR
electrospray positive spectrometer.

COBALT DITHIOCARBAMATE COMPLEXES FOR BIOLOGICAL STUDIES
3 of 15
2.3 | Synthesis of symmetric and
unsymmetric N,N-diarylformamidine
2.4.1 | Synthesis of DTL1
The reaction of L1 (1.00 g, 4 mmol), KOH (0.22 g,
4 mmol) and CS2 (0.24 ml, 4 mmol) in 20 ml of acetoni-
trile furnished dithiocarbamate ligand DTL1 as a
N,N0-Bis(2,6-dimethyphenyl)formamidine (L1), N,N0-
(2,6-diisopropylphenyl)formidine
(L2)
and
N,N0-
dimesitylformamidine (L3), the symmetric forms, were
synthesized following a procedure from the literature
with slight modifications.[38] A 50 ml round-bottom flask
was charged with 2 mmol of aniline, 1 mmol of triethyl
orthoformate and three to four drops of acetic acid. The
reaction mixture was refluxed at 140–160ꢀC for 2 h, after
which all volatiles were removed via distillation at 160ꢀC.
The reaction mixture was then allowed to cool, the crude
product washed with hexane and then collected by filtra-
tion. The solid obtained was recrystallized from 50 cm3 of
hot acetone.
yellow powder. Yield 87%. Decomposition temperature
1
237–242ꢀC. H NMR (DMSO, 400 MHz, δ, ppm): 1.90 (s,
6H, CH3 Ar), 1.99 (s, 6H, CH3 Ar), 6.91 (s, 3H, Ar H),
6.85 (d, 2H, JHH = 7.48 Hz, Ar H), 6.70 (t, 1H,
JHH = 7.48 Hz, Ar H), 9.86 (s, 1H, CH N). 13C NMR
(DMSO, 100 MHz, δ, ppm): 16.7, 17.3, 116.9, 121.0, 124.9,
126.0, 126.4, 126.5, 126.6, 134.1, 140.9, 148.3, 151.5, 217.62.
IR (ν, cm−1): 2918(w), 1640(s), 1467(s), 1000(s), 921(w).
UV–visible (CHCl3, λmax, nm): 292, 340. Anal. calcd for
(C18H20N2S2K).H2O (%): C, 56.21; H, 5.50; N, 7.28; S,
16.67. Found (%): C, 56.06; H, 5.75; N, 7.22; S, 16.20.
The unsymmetric forms N-(2,6-dichlorophenyl)-N-
(2,6-dimethylphenyl)formamidine
(L4),
N-(2,-
6-dichlorophenyl)-N-(2,6-diisopropylphenyl)formamidine
(L5) and (2,6-dichlorophenyl)-N-mesitylformamidine
(L6) were synthesized as follows. Two or three drops of
acetic acid were added to a round-bottom flask con-
taining 1 mmol of 2,6-dichloroaniline and 1 mmol of
triethyl orthoformate. The mixture was heated under
reflux and the temperature maintained at 140–160ꢀC for
2 h with stirring followed by distillation (2 mmol of EtOH
collected). The second aniline (1 mmol) was then added
to the reaction mixture and heating continued for 1 h
followed by distillation (1 mmol of EtOH collected).
Upon cooling to room temperature, the solution solidi-
fied. The crude product was washed with cold hexane to
remove unreacted anilines and then washed with 50 cm3
of dichloromethane to remove any traces of symmetric
formamidine byproducts that were formed during the
reaction.
2.4.2 | Synthesis of DTL2
The reaction of L2 (1.46 g, 4 mmol), KOH (0.22 g,
4 mmol) and CS2 (0.16 ml, 4 mmol) in 20 ml of acetoni-
trile furnished dithiocarbamate ligand DTL2 as a yellow
powder. Yield 74.18%. Decomposition temperature
1
244–249ꢀC. H NMR (DMSO, 400 MHz, δ, ppm): 1.06 (d,
12H, JHH = 6.88 Hz,
CH3 CH ), 1.14 (d, 6H,
JHH 6.88 Hz,
=
CH3 CH ), 1.21 (d, 12H,
JHH = 6.76 Hz, CH3 CH ), 2.84 (m, 2H, JHH = 6.72 Hz,
CH CH3), 2.97 (m, 2H, JHH = 6.84 Hz, CH CH3),
6.94 (t, 1H, JHH = 6.76 Hz, Ar H), 7.02 (d, 2H,
JHH = 7.12 Hz, Ar H), 7.11 (d, 2H, JHH = 7.50 Hz,
Ar H), 7.21 (t, 1H, JHH = 7.00 Hz, Ar H), 10.15 (s,
1H, CH N). 13C NMR (DMSO, 100 MHz, δ, ppm):
23.80, 24.00, 24.86, 26.58, 28.24, 122.47, 122.86, 127.08,
138.61, 138.87, 145.23, 147.49, 154.21, 220.94. IR (ν,
cm−1): 2959(s), 2865(w) 1639(s), 1452(s), 1152(s), 999(s).
UV–visible (CHCl3, λmax, nm): 293, 339. Anal. calcd for
(C26H35N2S2K) (%): C, 65.92; H, 7.37; N, 5.85; S, 13.39.
Found (%): C, 66.08; H, 7.69; N, 5.85; S, 12.20.
2.4 | Synthesis of N,N0-
diarylformamidine dithiocarbamate
ligands
Equimolar amounts of formamidine and KOH in 20 ml
of acetonitrile were stirred for 20 min in a cold mixture of
ice at 0–5ꢀC to form a white-colored solution. To the
resulting solution, carbon disulfide of the same molar
quantity was added dropwise with stirring for 4 h in an
ice bath to give a yellow solution. A rotary evaporator
was used to remove the solvent, giving a yellow crude
solid, which was then washed with ethanol three times to
remove the unreacted formamidine. The pure yellow
solid was dried at room temperature and stored in a des-
iccator.The 1H and 13C NMR data is provided in the sup-
plementary materials (Figures S1-S12).
2.4.3 | Synthesis of DTL3
The reaction of L3 (1.12 g, 4 mmol), KOH (0.22 g,
4 mmol) and CS2 (0.21 ml, 4 mmol) in 20 ml of acetoni-
trile furnished dithiocarbamate ligand DTL3 as a yellow
powder. Yield 93.63%. Decomposition temperature
1
258–263ꢀC. H NMR (DMSO, 400 MHz, δ, ppm): 1.94
(s, 6H, CH3 Ar), 2.03 (s, 6H, CH3 Ar), 2.15 (s, 3H,
CH3 Ar), 2.22 (s, 3H, CH3 Ar), 6.75 (s, 2H, Ar H), 6.81
(s, 2H, Ar H), 9.92 (s, 1H, CH N). 13C NMR (DMSO,
100 MHz, δ, ppm): 13.92, 17.70, 18.32, 20.29, 20.58, 127.26,
127.90, 128.30, 130.51, 134.82, 139.55, 147.10, 152.79,

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OLADIPO ET AL.
218.95. IR (ν, cm−1): 2951 (m), 1629(s), 1477(m), 1023(s),
956(w). UV–visible (CHCl3, λmax, nm): 289, 338. Anal.
calcd for (C20H23N2S2K) (%): C, 60.87; H, 5.87; N, 7.10; S,
16.25. Found (%): C, 60.41; H, 5.93; N, 6.95; S, 15.97.
JHH = 8.4 Hz, Ar H), 7.35 (d, 2H, JHH = 8.04 Hz, Ar H),
10.11 (s, 1H,CH N Ar). 13C NMR (DMSO, 100 MHz, δ,
ppm): 17.68, 20.59, 124.04, 126.34, 127.97, 128.32, 135.02,
135.12, 138.71, 146.17, 154.83, 219.04. IR (ν, cm−1):
2915(w), 1612(s), 1435(s), 1141(s), 1032(s). UV–
visible (CHCl3, λmax, nm): 295, 343. Anal. calcd for
(C17H15Cl2N2S2K).H2O (%): C, 46.46; H, 3.90; N, 6.37; S,
14.59. Found (%): C, 46.29; H, 4.05; N, 6.33; S, 14.26.
2.4.4 | Synthesis of DTL4
The reaction of L4 (1.17 g, 4 mmol), KOH (0.22 g,
4 mmol) and CS2 (0.25 g, 4 mmol) in 20 ml of acetonitrile
furnished dithiocarbamate ligand DTL4 as a yellow
powder. Yield 77%. Decomposition temperature
2.5 | Preparation of complexes
1
245–248ꢀC. H NMR (DMSO, 400 MHz, δ, ppm): 2.13
Each of the respective dithiocarbamate salts (3 mmol)
was dissolved in 20 ml of acetonitrile. To the resultant
solution, 1 mmol of anhydrous CoCl2 salt dissolved in
10 ml of water was added dropwise and stirred for about
20 min at 25ꢀC. The resultant green solids were collected
by filtration and dried at room temperature. The com-
plexes were then recrystallized from a solution in ethanol
heated to 80ꢀC and then allowed to cool to room temper-
ature. Each resulting solid precipitate was then collected
(s, 6H, CH3 Ar), 7.02 (s, 4H, Ar H), 7.39 (d, 2H,
JHH = 8.08 Hz, Ar H), 10.12 (s, 1H, CH N). 13C NMR
(DMSO, 100 MHz, δ, ppm): 17.76, 124.13, 126.37, 126.40,
127.26, 127.52, 127.73, 128.34, 135.23, 135.42, 141.29,
146.08, 154.81, 218.82. IR (ν, cm−1): 3177(w), 1614(s),
1432(s), 1128(s), 1033(s). UV–visible (CHCl3, λmax, nm):
293, 345. Anal. calcd for (C16H13Cl2N2S2K).2H2O (%): C,
45.17; H, 3.55; N, 6.58; S, 15.07. Found (%): C, 45.52; H,
3.81; N, 6.29; S, 15.19.
1
by filtration and dried in an oven at 60ꢀC. The H and
13C NMR data is provided in the supplementary materials
(Figures S13 - S24).
2.4.5 | Synthesis of DTL5
The reaction of L5 (1.40 g, 4 mmol), KOH (0.22 g,
4 mmol) and CS2 (0.21 g, 4 mmol) in 20 ml of
acetonitrile furnished dithiocarbamate ligand DTL5 as
a yellow powder. Yield 91%. Decomposition tempera-
2.5.1 | Synthesis of [Co-(DTL1)3] (1)
The reaction of DTL1 (0.30 g, 0.80 mmol) and CoCl2
(0.04 g, 0.27 mmol) in acetonitrile furnished complex 1 as
a green powder. Yield 81%. Decomposition temperature
1
ture 250–260ꢀC. H NMR (DMSO, 400 MHz, δ, ppm):
1
1.14 (t, 12H, JHH = 7.28 Hz, CH3 CH), 2.87 (m, 2H,
JHH = 6.76 Hz, CH Ar), 6.98 (t, 1H, JHH = 8.08 Hz,
Ar H), 7.10 (d, 2H, JHH = 7.56 Hz, Ar H), 7.21 (t,
1H, JHH = 7.24 Hz, Ar H), 7.38 (d, 2H, JHH = 8.08 Hz,
Ar H), 10.39 (s, 1H, CH N Ar). 13C NMR (DMSO,
100 MHz, δ, ppm): 26.81, 27.75, 27.98, 132.87, 133.98,
137.90, 138.48, 145.31, 146.14, 146.33, 151.41, 156.87,
217.02. IR (ν, cm−1): 2960 (w), 1603(s), 1430(s),
279–281ꢀC. H NMR (CDCl3, 600 MHz, δ, ppm): 2.18 (s,
36H, CH3 Ar), 6.89 (t, 3H, Ar H), 6.98 (d, 6H, Ar H),
7.19 (m, 6H, Ar H), 7.31 (m, 3H, Ar H), 8.85 (s, 2H,
CH N), 8.99 (s, 1H, CH N). 13C NMR (CDCl3,
150 MHz, δ, ppm): 17.85, 17.93, 18.75, 124.01, 127.82,
128.18, 128.91, 129.76, 134.19, 136.45, 144.44, 147.15,
212.97. IR (ν, cm−1): 2955(m), 1648(s), 1472(m), 1186(s),
888(s), 419(w). UV–visible (CHCl3, λmax, nm): 277 (shoul-
der), 309, 389, 490 (shoulder), 621. ESI-TOF MS: m/z (%)
1145(s), 1036(s). UV–visible (CHCl3, λmax
,
nm):
300, 345. Anal. calcd for (C20H21Cl2N2S2K).3H2O
(%): C, 46.41; H, 5.26; N, 5.41; S, 12.39. Found (%): C,
46.53; H, 5.55; N, 5.05; S, 12.59.
[M + 2Na −
2DTL1]+ 435.93. Anal. calcd for
(C54H60N6S6Co).2H2O (%): C, 60.03; H, 5.97; N, 7.78; S,
17.80. Found (%): C, 59.31; H, 5.58; N, 7.52; S, 17.25.
2.4.6 | Synthesis of DTL6
2.5.2 | Synthesis of [Co-(DTL2)3] (2)
The reaction of L6 (1.23 g, 4 mmol), KOH (0.22 g, 4 mmol)
and CS2 (0.24 g, 4 mmol) in 20 ml of acetonitrile furnished
dithiocarbamate ligand DTL6 as a yellow powder. Yield
83%. Decomposition temperature 255–258ꢀC. 1H NMR
(DMSO, 400 MHz, δ, ppm): 2.07 (s, 6H, CH3 Ar N ),
2.23 (s, 3H, CH3 Ar), 6.81 (s, 2H, Ar H), 7.00 (t, 1H,
The reaction of DTL2 (0.30 g, 0.60 mmol) and CoCl2
(0.03 g, 0.2 mmol) in acetonitrile furnished complex
2 as a green powder. Yield 77%. Decomposition tem-
1
perature 287–289ꢀC. H NMR (CDCl3, 600 MHz): 1.19
(m, 72H, CH3 CH), 2.85 (m, 12H, CH CH3), 7.10 (t,
10H, Ar H), 7.28 (t, 5H, Ar H), 7.47 (t, 5H, Ar H),

COBALT DITHIOCARBAMATE COMPLEXES FOR BIOLOGICAL STUDIES
5 of 15
8.99 (t, 3H, CH N). 13C NMR (CDCl3, 150 MHz, δ,
ppm): 24.07, 24.25, 25.09, 25.32, 25.72, 27.59, 29.12,
29.26, 123.08, 123.17, 124.55, 130.42, 130.81, 138.94,
139.06, 145.07, 145.23, 145.42, 146.75, 146.88, 214.81.
IR (ν, cm−1): 2961(m), 1647(s), 1469(m), 1185(s),
a green powder. Yield 79%. Decomposition temperature
1
305–307ꢀC. H NMR (CDCl3, 600 MHz): 1.25 (m, 36H,
CH3 CH), 2.79 (m, 6H, CH CH3), 6.94 (t, 3H, Ar), 7.28
(d, 11H, Ar H), 7.48 (s, 4H, Ar H), 9.20 (s, 3H, CH N).
13C NMR (CDCl3, 150 MHz, δ, ppm): 24.28, 24.76, 25.49,
28.95, 124.79, 125.04, 126.95, 128.44, 130.19, 130.58,
144.37, 147.03, 148.84, 215.80. IR (ν, cm−1): 2921(m),
1646(s), 1469(m), 1194(s), 889(s), 418 (w). UV–visible
(CHCl3, λmax, nm): 277 (shoulder), 313, 388, 482 (shoul-
der), 629. ESI-TOF MS: m/z (%) [M + H]+ 1371.12. Anal.
calcd for (C60H66Cl6N6S6Co) (%): C, 53.97; H, 4.98; N,
6.29; S, 14.41. Found (%): C, 53.61; H, 4.41; N, 6.21; S,
14.26.
888(s), 418(w). UV–visible (CHCl3, λmax
,
nm):
278 (shoulder), 307, 388, 494 (shoulder), 632. ESI-TOF
MS: m/z (%) [M − DTL2]+ 939.40. Anal. calcd for
(C78H108N6S6Co) (%): C, 67.84; H, 7.88; N, 6.09; S,
13.93. Found (%): C, 67.51; H, 7.44; N, 5.88; S, 13.43.
2.5.3 | Synthesis of [Co-(DTL3)3] (3)
The reaction of DTL3 (0.30 g, 0.80 mmol) and CoCl2
(0.04 g, 0.27 mmol) in acetonitrile furnished complex
3 as a green powder. Yield 79%. Decomposition temper-
2.5.6 | Synthesis of [Co-(DTL6)3] (6)
1
ature 269–271ꢀC. H NMR (CDCl3, 600 MHz): 2.19 (m,
The reaction of DTL6 (0.30 g, 0.80 mmol) and CoCl2
72H, CH3 CH), 6.79 (t, 6H, Ar H), 6.97 (s, 1H,
Ar H), 7.03 (d, 5H, Ar H), 8.82 (d, 2H, CH N), 8.96
(s, 1H, CH N). 13C NMR (CDCl3, 150 MHz, δ, ppm):
17.75, 17.83, 18.66, 20.66, 21.32, 127.66, 128.78, 129.75,
131.56, 133.22, 135.94, 139.62, 144.85, 213.07. IR (ν,
cm−1): 2920(m), 1646(s), 1473(m), 1190(s), 890(s),
420(w). UV–visible (CHCl3, λmax, nm): 275 (shoulder),
305, 387, 497 (shoulder), 618. ESI-TOF MS: m/z (%)
[M − DTL3]+ 771.21. Anal. calcd for (C60H72N6S6Co)
(%): C, 63.86; H, 6.43; N, 7.45; S, 17.04. Found (%): C,
63.22; H, 6.17; N, 7.36; S, 16.57.
(0.04 g, 0.26 mmol) in acetonitrile furnished complex 6 as
1
a green powder. Yield 79%. Melting point 290–292ꢀC. H
NMR (CDCl3, 600 MHz): 2.24 (m, 27H, CH3 Ar), 6.97
(m, 10H, Ar H), 7.27 (s, 3H, Ar H), 9.01 (d, 3H, CH N).
13C NMR (CDCl3, 150 MHz, δ, ppm): 17.77, 21.36, 125.07,
126.85, 128.24, 129.76, 130.85, 136.23, 139.98, 144.19,
147.46, 213.92. IR (ν, cm−1): 2921(m), 1647(s), 1468(m),
1193(s), 889(s), 419 (w). UV–visible (CHCl3, λmax, nm):
277 (shoulder), 310, 387, 490 (shoulder), 625. ESI-TOF
MS: m/z (%) [M + H]+ 1244.85. Anal. calcd for
(C48H42Cl6N6S6Co) (%): C, 50.67; H, 4.00; N, 6.95; S, 15.91.
Found (%): C, 50.38; H, 3.53; N, 6.64; S, 15.78.
2.5.4 | Synthesis of [Co-(DTL4)3] (4)
2.6 | Single-crystal X-ray diffraction
The reaction of DTL4 (0.30 g, 0.80 mmol) and CoCl2
(0.04 g, 0.27 mmol) in acetonitrile furnished complex 4 as
a green powder. Yield 84%. Decomposition temperature
Structure refinement parameters as well as the crystallo-
graphic data for complexes 1, 2, 4 and 5 are given in
Table 1. Evaluation of crystals and collection of data
were done using a Bruker Smart APEXII diffractometer,
with Mo Kα radiation (λ = 0.71073 Å). This was equipped
with an Oxford Cryostream low-temperature apparatus
operating at 100 K. Reflections were collected at
different starting angles and the APEXII program suite
was used to index the reflections.[39] Reduction of data
was carried out using SAINT software[40] and absorption
corrections and scaling were applied using the
SADABS multi-scan technique.[41] The four structures
were solved by direct method using the SHELXS program
and refined using the SHELXL program.[42] Graphics of
the crystal structures were drawn using Mercury soft-
ware.[43] Non-hydrogen atoms were first refined iso-
tropically and then by anisotropic refinement with the
full-matrix least-squares method based on F2 using
SHELXL. One of the coordinated DTL4 molecules in
1
284–286ꢀC. H NMR (CDCl3, 600 MHz): 2.24 (m, 18H,
CH3 CH), 6.93 (m, 3H, Ar H), 7.27 (m, 15H, Ar H),
8.96 (s, 2H, CH N), 9.10 (s, 1H, CH N). 13C NMR
(CDCl3, 150 MHz, δ, ppm): 17.78, 21.37, 125.09, 126.86,
128.89, 129.78, 130.88, 136.27, 136.69, 139.99, 144.20,
147.45, 213.94. IR (ν, cm−1): 2919(m), 1645(s), 1474(m),
1191(s), 882(s), 417 (w). UV–visible (CHCl3, λmax, nm):
278 (shoulder), 309, 385, 487, 631 ESI-TOF MS: m/z (%)
[M + 2 K]+ 1242.85. Anal. calcd for (C48H42Cl6N6S6Co)
(%): C, 49.41; H, 3.63; N, 7.20; S, 16.48. Found (%): C,
48.96; H, 3.39; N, 7.18; S, 16.14.
2.5.5 | Synthesis of [Co-(DTL5)3] (5)
The reaction of DTL5 (0.30 g, 0.70 mmol) and CoCl2
(0.03 g, 0.24 mmol) in acetonitrile furnished complex 5 as

6 of 15
OLADIPO ET AL.
TABLE 1 Summary of X-ray crystal data collection and structure refinement parameters for complex 1, 2, 4 and 5
1
2
4
5
Empirical formula
C54H57CoN6S6
1041.34
Trigonal
R-3:H
C78H105CoN6S6
1377.96
Monoclinic
P21/c
C48.04H39Cl6CoN6S6
1164.32
C60H63Cl6CoN6S6
1332.15
Formula weight
Crystal system
Space group
a (Å)
Triclinic
P-1
Triclinic
P-1
18.0869(3)
18.0869(3)
32.8086(6)
90
18.4354(4)
23.9108(5)
18.7970(4)
90
14.3904(9)
14.6123(9)
16.4524(9)
91.839(2)
113.978(2)
116.2640(10)
2738.2(3)
2
16.5248(3)
17.0460(4)
17.2205(5)
65.378(2)
63.9490(10)
66.828(3)
3827.78(19)
2
b (Å)
c (Å)
α (ꢀ)
β (ꢀ)
90
111.2040(10)
90
γ (ꢀ)
V (Å3)
120
9294.9(4)
6
7724.9(3)
4
Z
ρcalc (g cm−3
)
1.116
1.185
1.412
1.156
μ (mm−1
)
0.295
0.429
0.874
0.633
F(000)
3276.0
2952.0
1182
1380
Crystal size (mm3)
0.22 × 0.15 × 0.13
1.44 to 28.39
0.22 × 0.14 × 0.08
3.406 to 55.3
0.31 × 0.18 × 0.14
1.707 to 28.376
0.28 × 0.14 × 0.09
1.694 to 28.272
2θ range for data collection
(ꢀ)
Index ranges
22 ≤ h ≤ 24
−24 ≤ k ≤ 18
−43 ≤ l ≤ 42
20111
−23 ≤ h ≤ 24
−31 ≤ k ≤ 31
−24 ≤ l ≤ 24
91538
−16 ≤ h ≤ 19
−19 ≤ k ≤ 18
−21 ≤ l ≤ 18
38071
−22 ≤ h ≤ 21
−22 ≤ k ≤ 19
−22 ≤ l ≤ 22
55172
Reflections collected
Independent reflections
Data/restraints/parameters
Goodness-of-fit on F2
5151 [Rint = 0.0271]
5151/0/206
1.110
17942 [Rint = 0.0372]
17942/0/844
1.020
13330 [Rint = 0.018]
13330/66/758
1.087
18644 [Rint = 0.0174]
18644/3/724
1.046
Final R indexes [I > =2σ(I)]
R1 = 0.0421,
wR2 = 0.1088
R1 = 0.0374,
wR2 = 0.0802
R1 = 0.0461,
wR2 = 0.1092
R1 = 0.0413,
wR2 = 0.1065
Final R indexes [all data]
R1 = 0.0506,
wR2 = 0.1123
R1 = 0.0649,
wR2 = 0.0922
R1 = 0.0461,
wR2 = 0.1092
R1 = 0.0578,
wR2 = 0.1092
Largest diff. peak and hole
0.39 and −0.36
0.39 and −0.270
0.774 and −1.170
1.996 and −1.379
(e Å−3
)
complex 4 was found to be disordered over two positions
with the major components having 50.8% and 58.7% site
occupancy. In complex 4 and 5, solvent masks were cal-
culated and 35.0 electrons were found in a void with a
volume of 179.0 Å3 in 4, consistent with the presence of
0.33[C6H6] per formula unit which account for 33.0 elec-
trons. 298.0 electrons were found in a void with a volume
of 920 Å3 in 5, consistent with the presence of 3[C6H14]
per formula unit accounting for 300.0 electrons. The sol-
vent molecules were of hexane in both complexes 4 and
5 and were highly disordered. Attempts to model them
were unsuccessful and only led to unstable refinement
and were therefore omitted using the SQUEZE option[44]
in PLATON.[45]
2.7 | In vitro antimicrobial studies
The antimicrobial activity of the Co(III) dithiocarbamate
complexes was investigated against two Gram-positive
bacteria, i.e. Staphylococcus aureus ATCC 25923 and
Staphylococcus aureus ATCC 700699 (methicillin resis-
tant); and four Gram-negative bacteria, i.e. Klebsiella
pneumoniae ATCC 31488, Salmonella typhimurium
ATCC 14026, Pseudomonas aeruginosa ATCC 27853 and
Escherichia coli ATCC 25922. Ciprofloxacin was used as a
standard and DMSO as the negative control. The samples
were prepared by dissolving 1000 μg of sample in 1 ml of
DMSO. The streak plate technique was used to inoculate
the bacteria onto Nutrient Agar (Biolab, South Africa)

COBALT DITHIOCARBAMATE COMPLEXES FOR BIOLOGICAL STUDIES
7 of 15
and incubated at 37ꢀC for 18 h. Thereafter, a single
colony was isolated and inoculated into 10 ml sterile
Nutrient Broth (Biolab, South Africa). This was incubated
at 37ꢀC for 18 h in a shaking incubator (100 rpm). The
concentration of each bacterial strain was adjusted
with sterile distilled water to achieve a final concentra-
radical scavenging assay in order to determine the antiox-
idant activity of the compounds following a slightly mod-
ified method of Chandrika et al.[47] All solutions were
freshly prepared. An amount of 100 μl of a 0.1 mM DPPH
solution in ethanol was added to equal quantities of the
compounds and complexes at different concentrations
(1.0, 0.75, 0.50 and 0.25 mM). The reaction mixture was
vortexed cautiously and kept in the dark at 25ꢀC for
30 min. After incubating the mixture for 30 min at 25ꢀC,
the DPPH reduction was measured by measuring the
absorbance at 517 nm. Ascorbic acid of the same concen-
trations as the test samples was used as standard. The
experiments were run in triplicate and the results aver-
aged. The ability of the compounds to scavenge DPPH
radical was calculated as per Equation (1):
tion
equivalent
to
0.5
McFarland
standard
(i.e. 1.5 × 108 cfu ml−1) using a densitometer (McFarland
Latvia).[46] The MHA plates were then lawn-inoculated
with the diluted bacteria using a sterile throat swab. An
amount of 5 μl of each sample was spotted onto the MHA
plates and the plates were incubated at 37ꢀC for 18 h.
The plates were then assessed for antibacterial activity,
which was denoted by a clear zone at the point of spot-
ting. Samples that showed antimicrobial potential during
antibacterial screening were investigated further to deter-
mine their minimum inhibitory concentration (MICs).
The samples were serially diluted 10 times to achieve
concentrations ranging from 1000 to 0.2 μg ml−1. For
samples with MICs lower than 0.2 μg ml−1, the solutions
were further diluted serially five times to achieve concen-
trations ranging from 0.100 to 0.00625 μg ml−1. An
amount of 5 μl of each sample at different concentrations
was spotted onto the MHA plates and treated in a man-
ner similar to that for previous dilutions prior to assess-
ment of their MICs. The experiments were done in
triplicate, determining the MIC values as the lowest con-
centration of the compounds at which no visible bacterial
growth was observed after incubation.
ðAbsorbance of control−absorbance of sampleÞ × 100
Scavenging activity ð%Þ =
Absorbance of control
ð1Þ
3 | RESULTS AND DISCUSSION
3.1 | Syntheses
The synthesis routes for the potassium salts DTL1–DTL6
and their cobalt complexes 1–6 are shown in Scheme 1.
DTL1–DTL6 were obtained from the reactions of
equimolar amounts of the appropriate precursors L1–L6
with carbon disulfide and potassium hydroxide at 4ꢀC.
The respective reaction mixtures were stirred for 5 h to
furnish DTL1–DTL6 in good yields of between 74% and
94% as yellow solids. Initial indicators of the products
were the melting points, which were different from those
of L1–L6 and ranged between 237 and 263ꢀC. Complexes
2.8 | Determination of free radical
scavenging activity
Complexes 1–6 and their respective ligands were sub-
jected to 1,1-diphenyl-2-picrylhydrazyl (DPPH) free
SCHEME 1 Synthesis of potassium dithiocarbamate salts of formamidines (DTL1–DTL6) and the respective Co(III) N,N0-
diarylformamidine dithiocarbamate complexes (1–6)

8 of 15
OLADIPO ET AL.
1–6 were also obtained in high yields (77–84%) by the
reactions of DTL1–DTL6 with CoCl2 in a 3:1 ratio to give
air-stable green solids. The complexes had decomposition
temperatures of 269–305ꢀC, the complexes with the
unsymmetric formamidine dithiocarbamate backbones
being more thermally stable compared to their symmetric
counterparts. All complexes showed good solubility in
benzene, toluene, tetrachloromethane, dichloromethane
and chloroform but were only partially soluble in other
polar solvents.
3.2.2 | IR spectroscopy
The IR spectra for 1–6 (See Figures S31-36) exhibit
three characteristic vibrational bands, ν(C S),
ν(N CS2) and metal-to-sulfur bond (M S) typical of
dithiocarbamate complexes[18,20,21,53–55] in literature,
and ν(C Nstr) of the azomethine (C(H) N).[56] In the
spectra of the dithiocarbamate metal complexes, the
ν(C S) band appears at around 950–1050 cm−1 and
defines the bonding mode of the dithiocarbamate moi-
ety to the metal center. A single peak in this region is
typical of bidentate coordination.[57] The spectra of all
six complexes displayed a sharp peak at around
999–1018 cm−1. The ν(N CS2) thiouride band was
3.2 | Spectroscopic studies
3.2.1 | NMR spectroscopy
observed at
a
higher frequency of around
1468–1479 cm−1 different from those of the dithiocar-
bamate salts (DTL1–DTL6) observed at around
1430–1477 cm−1. These values are intermediate of the
stretching frequencies associated with C N single
1
The H NMR data for DTL1–DTL6 and those of com-
plexes 1–6 were all obtained with samples in DMSO
and in chloroform, respectively. The azomethine pro-
ton (NC(H) N) was used to follow the successful syn-
thesis of the cobalt(III) complexes from potassium
dithiocarbamate salts where an upfield shift from
9.86–10.39 ppm in the spectra DTL1–DTL6 to between
8.82 and 9.20 ppm in the spectra of 1–6 confirmed
complexation. Other notable shifts were observed for
the aliphatic protons. For example, the signal for the
methyl protons (CH3 Ar) in DTL1 appeared at 1.99
and 1.90 ppm but, upon complexation, a downfield
shift to 2.18 ppm was observed in the spectrum of
complex 1. This downfield shift is due the drift of elec-
tron density towards the Co(III) center in the com-
plexes.[48,49] Also, the peaks of the quaternary
thiouride carbon atom ( NCS2) in the 13C NMR spec-
tra of 1–6 further confirmed formation of DTL1–DTL6
and these generally were observed to shift upfield
upon complexation (Table 2). This observation is
attributed to metal–sulfur bond formation and the
delocalization of an electron cloud in the four-member
(CS2M) chelate ring.[50–52]
bond (1250–1350 cm−1
)
and C N double bond
(1640–1690 cm−1). This is an indication of partial dou-
ble bond character of C N (thiouride bond) in 1–6.
The shift to higher frequency in the complex compared
to the ligand could be due mesomeric drift of electrons
from the dithiocarbamate moiety towards the metal
coordination center.[58] In addition, a strong vibrational
band appeared in the region of 1645–1648 cm−1 in the
spectra of all the complexes and this can be associated
with ν(C Nstr) of azomethine in the complexes. It
was observed to shift towards higher vibrational fre-
quencies for all the complexes (Table 2). The observed
shifts could be attributed to an increase in π-electron
density in C Nstr upon coordination rendering the
C N bond resonating at higher frequency. This also
confirms that the nitrogen atom in the dithiocarbamate
ligand does not coordinate with the metal center. The
Co S stretching vibration was assigned to the bands
that appeared in the far-IR region at around
416–420 cm−1
.
TABLE 2 The NCS2 13C NMR signals for DTL1–DTL6 and 1–6, and the IR bands of thiouride (C N) and azomethine (C N) for
ligands and complexes
Ligand (complex)
DTL1 (1)
δ ( NCS2)
Δδ
ν(C N) (cm−1
1640 (1648)
1639 (1647)
1629 (1646)
1614 (1645)
1603 (1646)
1612 (1647)
)
Δν
8
ν(C N) (cm−1
1467 (1472)
1452 (1469)
1477 (1479)
1432 (1474)
1430 (1469)
1435 (1468)
)
Δν
7
217.62 (212.97)
220.94 (214.81)
218.95 (213.07)
218.82 (213.94)
217.02 (215.80)
219.04 (213.92)
4.65
6.13
5.88
4.88
1.22
5.12
DTL2 (2)
8
8
DTL3 (3)
17
31
43
35
1
DTL4 (4)
3
DTL5 (5)
5
DTL6 (6)
1

COBALT DITHIOCARBAMATE COMPLEXES FOR BIOLOGICAL STUDIES
9 of 15
3.2.3 | UV–visible spectroscopy
literature.[21,60,61] Other high-energy absorption bands
which appeared at around 275, 305 and 389 nm are
assigned to intraligand charge transfer transitions. Com-
The electronic absorption spectra of the dithiocarba-
mate ligands and the metal complexes were recorded in
DMSO and chloroform, respectively. The UV–visible
spectra of all the ligands and the six complexes are
shown in Figure 1. Transitions due to the ligands
appeared in the UV region while the d–d transitions
appeared in the visible region.[25] The spectra of the
ligands DTL1–DTL6 showed two absorption bands in
the UV region between 289 and 300 nm and between
338 and 345 nm. These absorption bands are assigned
to intraligand π ! π* associated with the N C S
group and π ! π* transition within the S C S
group.[59] However, five absorption bands were
observed in the electronic spectra of 1–6 at 275–278,
305–313, 385–389, 482–494 and 618–631 nm. Low-
intensity broad bands at around 482 and 631 nm are
assigned to d–d transition consistent with the
paring the data obtained from the electronic spectra of
[21,62]
1–6 with those readily available for Co(dtc)3
sug-
gests an octahedral geometry around the coordination
metal center.
3.3 | Single-crystal X-ray structural
analysis
Suitable crystals for single-crystal X-ray structural anal-
ysis were obtained by slow evaporation from a dic-
hloromethane solution for complexes 1, 2 and 5, and
by vapor diffusion of hexane into dichloromethane
solution for complex 4. The molecular structures are
shown in Figure 2 while selected bond distances and
angles are listed in Table 3. Each asymmetric unit of
FIGURE 1 Electronic
absorption spectra of (a) DTL1–
DTL6, (b) 1–6 and (c) 1–6 showing
the broad region of d–d transition
FIGURE 2 ORTEP diagrams of
complexes 1, 2, 4 and 5 drawn at 50%
thermal ellipsoid probability. Hydrogen
atoms have been omitted for clarity

10 of 15
OLADIPO ET AL.
TABLE 3 Selected bond lengths (Å) and angles (ꢀ) for complexes 1, 2, 4 and 5
1
2
4
5
Bond lengths
Co–S(1)
2.2581(6)
2.2581(6)
2.2582(6)
2.2621(6)
2.2622(6)
2.2621(6)
2.2642(5)
2.2747(5)
2.2293(5)
2.2586(5)
2.2414(5)
2.2508(5)
2.2602(7)
2.2708(7)
2.2595(9)
2.2612(7)
2.2418(8)
2.2764(9)
2.2609(5)
2.2655(5)
2.2510(5)
2.2802(5)
2.2489(5)
2.2707(5)
Co–S(2)
Co–S(3)
Co–S(4)
Co–S(5)
Co–S(6)
Bond angles
S(1)–Co(1)–S(2)
S(3)–Co(1)–S(4)
S(5)–Co(1)–S(6)
76.726(18)
76.726(18)
76.728(18)
76.974(17)
76.807(17)
76.685(17)
76.91(2)
76.87(3)
76.88(2)
76.761(6)
76.758(19)
76.691(18)
2, 4 and 5 contains a whole molecule of the cobalt
dithiocarbamate complex, while that of 1 only has
one-third of the cobalt complex. All four complexes
are mononuclear with the Co(III) center coordinated
to six sulfur atoms from three dithiocarbamate ligands,
the ligands coordinating in a bidentate fashion. In that
manner, three four-member CS2Co chelate rings are
formed, each with a bite angle of between 76.69(17)ꢀ
and 76.97(17)ꢀ (Table 4). The ligand bite angle and the
other angles around the metal center deviate signifi-
cantly from those of an ideal octahedral geometry.[22]
Interestingly, the S Co S bite angle is smaller in the
complexes reported herein (all ca 76ꢀ and 77ꢀ) com-
pared to those of cobalt dithiophosphate complexes
reported in the literature (all above 81ꢀ). The Co S
bond distances are however very comparable.[62,63] The
C S bond distances fall between ideal single and dou-
ble C S bonds indicating partial delocalization of π-
electron density around the S C(N) S fragment.[18]
The delocalization is also extended to the C N bond
of the S2CN fragment in the complexes, as also
observed in the literature.[21,64]
TABLE 4 Minimum inhibitory concentration of ligands and complexes (μg ml−1
Gram (−) bacteria
)
Gram (+) bacteria
Compound
E. coli
S. typhimurium
P. aeruginosa
K. pneumoniae
S. aureus
MRSA
Symmetric ligands and cobalt(III) complexes
DTL1
50
1000
1000
1000
1000
1000
1000
1000
1000
3.125
12.5
50
NAa
NA
NA
NA
NA
NA
NA
NA
DTL2
12.5
12.5
12.5
3.125
0.40
0.20
0.025
1.60
DTL3
NA
1
2
3
1000
1000
1000
0.80
1.6
1.60
3.125
Unsymmetric ligands and cobalt(III) complexes
DTL4
3.125
6.25
12.5
50
100
1000
1000
0.20
0.40
0.40
0.8
6.25
0.20
NA
NA
NA
1000
100
100
25
NA
NA
NA
NA
NA
NA
25
DTL5
DTL6
1.60
100
6.25
12.5
4
3.125
0.025
0.10
0.80
5
0.20
0.05
0.40
0.00625
0.10
6
Ciprofloxacinb
0.20
1.60
aNA, no activity.
bStandard reference.

COBALT DITHIOCARBAMATE COMPLEXES FOR BIOLOGICAL STUDIES
11 of 15
In addition, the C N bond length of the S2CN frag-
ments of the complexes deviates from the reported value
for single C N, which is 1.47 Å.[57] For example, C(13)
(N)2 = 1.369(2) Å, C(33) N(3) = 1.369(2) Å and C(53)
N(5) = 1.366(2) Å for complex 5, this affirming the delo-
calization of π-electrons over the entire S2CN fragment in
the complexes.[18]
the reference drug. However, none of the compounds
exhibited antimicrobial activity against MRSA and they
only displayed activity against S. aureus at high concen-
trations (100–1000 μg ml−1). The lack of activity of all the
complexes against MRSA could be as a result of the com-
plexes being modified or damaged as they enter the cell
wall of MRSA.[74]
It was observed that the complexes in which the
formamidine bore an electron-withdrawing group (Cl in
this instance), namely 4–6, had greater antimicrobial
activity than their counterparts which bore no chlorine
(1–3). This greater activity can be attributed to better
lipophilicity in the Cl-substituted complexes, hence more
easily penetrating into the lipophilic domains of proteins
or lipophilic section of cell membranes.[75] The chlorine
atoms in 4–6 could also help in the fixation of an active
molecular conformation which is necessary for interac-
tion with proteins in bacteria.[76]
3.4 | Antimicrobial studies
The literature has it that the chelation of ligands with
metal ions in some instances increases the biological
activities of the ligands[65–67] based on chelation the-
ory.[68] One attribute of chelation is that it increases the
lipophilic character of the resulting metal chelate which
leads to the enhancement of permeability of complexes
through lipid layers of cell membranes. In the study
reported here, we observed a similar phenomenon with
the cobalt(III) complexes formed having enhanced bio-
logical activities compared to free ligands. It may be
suggested that these complexes act by deactivating vari-
ous cellular enzymes which play crucial roles in various
metabolic pathways of organisms or denaturing one or
more proteins of the cell which destroy the normal cel-
lular processes.[69] The results for the antimicrobial
activities of the dithiocarbate ligands DTL1–DTL6 and
their complexes 1–6 are presented in Table 4. The activi-
ties of these compounds against six different types of
bacteria, namely Staphylococcus aureus, methicillin-
resistant Staphylococcus aureus (MRSA), Klebsiella
pneumoniae, Salmonella typhimurium, Pseudomonas
aeruginosa and Escherichia coli, were studied using cip-
rofloxacin as a reference drug. The MIC values were
used to evaluate their antibacterial activity and results
were compared with the standard. The lower the MIC
values the higher will be the antibacterial
potential.[70–73] The results based on the MICs obtained
show that the free ligands have lower antimicrobial
activities against the six bacterial strains when com-
pared to ciprofloxacin with the exception of DTL3 and
DTL5 which are more active against K. pneumoniae
than ciprofloxacin. In contrast to the parent ligands, the
complexes show moderate to excellent antimicrobial
activity compared to the reference drug, most especially
towards Gram-negative bacteria.
3.5 | Antioxidant studies
3.5.1 | DPPH radical scavenging ability
Compounds with antioxidant activity have the ability
to slow or completely prevent oxidative damage in the
body. Diseases such as Parkinson's disease, diabetes,
Alzheimer's disease, asthma and cancer have a high pos-
sibility of occurring because of oxidative damage.[77] The
antioxidant activities of dithiocarbamate salts and their
metal complexes have been reported.[78,79] The ability of
dithiocarbamates and metal complexes to scavenge free
radicals may probably be due to the presence of the sulfur
atoms on the dithiocarbamate ligand, which have the
capability of donating electrons, and to the presence of
transition metal ions in the complexes, which can stabi-
lize free radicals.[79] The loosely held electrons of dithio-
carbamate metal complexes can also stop or slow the
propagation of free radicals.[78]
DPPH assay is one of the commonly used methods for
fast evaluation of antioxidant activity due to its simplic-
ity.[70] It was used in the study reported here to deter-
mine the free radical scavenging ability of the
dithiocarbamate salts DTL1–DTL6 and their Co(III) com-
plexes 1–6. DPPH has an unpaired electron in its struc-
ture and the ability of any antioxidant compounds to
scavenge this electron depends on the electron or hydro-
gen radical donating ability.[80,81] In its radical form,
DPPH is known to have a strong absorption at 517 nm
giving a purple color, which turns to yellow upon reduc-
tion by an antioxidant compound to form reduced DPP-
H.[25,77] Previous studies have shown that complexes
exhibit better antioxidant activities compared to their
All the complexes were active against E. coli and
S. typhimurium, with complexes 5 and 6 showing better
activity compared to ciprofloxacin and the other com-
pounds. Complexes 4, 5 and 6 showed better activity
against P. aeruginosa relative to others as well as cipro-
floxacin. All the complexes together with DTL3 and
DTL5 showed better activity against K. pneumoniae than

12 of 15
OLADIPO ET AL.
parent ligands because the presence of a metallic moiety
enhances their proton donor ability.[82,83]
of 1.01 × 10−3 mM). The higher the IC50 values the lower
will be the antioxidant activity.[84,85] We found that all
the dithiocarbamate salts have extremely high IC50
values, which indicate their poor antioxidant activity.
However, their antioxidant activity increases upon coor-
dination with Co(III). Complex 2 has the lowest IC50
value and therefore the highest antioxidant activity,
followed by 1, 3, 4 and 6 in that order, while complex
5 has the highest IC50 value with the least antioxidant
activity. The IC50 values of complexes 1 and 2 are less
than that of ascorbic acid, suggesting that they are better
antioxidants than ascorbic acid.
The complexes in which the formamidine bears an
electron-donating group (alkyl group in this instance) on
both aromatic rings, namely 1–3, seem to have better
antioxidant activity than their counterparts (4–6) which
bear an electron-withdrawing group (Cl in this instance)
on one of the aromatic rings of the formamidine. For
example, complexes 1 and 2 have higher antioxidant
potential when compared to 4 and 5 (Table 5). It has been
The IC50 values of DTL1–DTL6 and 1–6 were calcu-
lated using their free radical scavenging ability values
and these are presented in Table 5. The IC50 values were
used to evaluate the antioxidant activity and results were
compared with a standard, ascorbic acid (with IC50 value
TABLE 5 Antioxidant potential of ligands and complexes
Ligand
DTL1
IC50 (mM)
2.14
Complex
IC50 (mM)
9.93 × 10−4
2.84 × 10−4
1.61 × 10−3
8.08 × 10−3
4.71 × 10−2
7.39 × 10−3
1.04 × 10−3
1
2
3
4
5
6
DTL2
4.11
DTL3
6.14
DTL4
5.71
DTL5
8.69
DTL6
18.28
1.04 × 10−3
Ascorbic acid
Ascorbic acid
Results are the mean values from three independent experiments.
FIGURE 3 Free radical scavenging
activity versus concentration of
potassium dithiocarbamate salts (DTL1–
DTL6)
FIGURE 4 Free radical scavenging
activity versus concentration of Co(III)
dithiocarbamate complexes (1–6)

COBALT DITHIOCARBAMATE COMPLEXES FOR BIOLOGICAL STUDIES
13 of 15
shown previously that electronic factors play a crucial
role in enhancing antioxidant activity.[86] In 1–3 the pres-
ence of electron-donating groups increases the electron
density at the carbon atoms in the aromatic rings of the
complexes, hence increasing their electron-donating
capability which leads to their higher antioxidant activity
relative to 4–6 that have electron-withdrawing groups.
Generally, the antioxidant activities of all the complexes
as well as the dithiocarbamate ligands increase as
the concentration increases, and this is illustrated in Fig-
ures 3 and 4.
Bernard Omondi https://orcid.org/0000-0002-3003-
6712
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CCDC 1917358, CCDC 1917359, CCDC 1917360 and
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
How to cite this article: Oladipo SD, Omondi B,
Mocktar C. Co(III) N,N0-diarylformamidine
dithiocarbamate complexes: Synthesis,
characterization, crystal structures and biological
studies. Appl Organometal Chem. 2020;e5610.
https://doi.org/10.1002/aoc.5610