Synthesis, X-ray structures, electrochemical properties and cytotoxic effects of Co(II) complexes

Article abstract of DOI:10.1016/j.ica.2010.03.011

1-Benzothiazol-2-yl-3,5-dimethyl-1H-pyrazole (1a) and 1-benzothiazol-2-yl- 5-(2-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboxylic acid methyl ester (1b) were reacted with the hexahydrates of cobalt(II) chloride, cobalt(II) nitrate and cobalt(II) perchlorate to give the corresponding complexes 2a-4a and 2b-5b, respectively. Obtained compounds differ in coordination spheres of central atoms. The complex 2a includes a fivefold coordinated cobalt(II) ion, whereas 3a shows a distorted octahedral configuration around the cobalt(II) ion. All complexes were characterised by FTIR spectroscopy, MS and elemental analysis. The X-ray structures of 2a, 3a and 5b complexes were also solved. The cytotoxic properties of the ligand 1a and both series of Co(II) complexes were examined on human leukemia NALM-6 and HL-60 cells and melanoma WM-115 cells. The ligands, were found to have very low cytotoxicity. Complex 3b exhibited the highest cytotoxic activity with IC₅₀ values in the range of 6.9-17.1 μM for three examined cell lines.

Full text of DOI:10.1016/j.ica.2010.03.011

Inorganica Chimica Acta 363 (2010) 2171–2179
Contents lists available at ScienceDirect
Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Synthesis, X-ray structures, electrochemical properties and cytotoxic effects
of Co(II) complexes
Marta Sobiesiak a, Krzysztof Sobiesiak a, Agnieszka Mrozek b, Peter Mayer c, Ingo-Peter Lorenz c,
Marek Rozalski d, Urszula Krajewska d, Elzbieta Budzisz a,e,
*
a Collegium Medicum in Bydgoszcz, Nicholaus Copernicus University in Torun, Faculty of Pharmacy, Department of Inorganic and Analytical Chemistry, 85-094 Bydgoszcz, Poland
b
´
Institute of General and Ecological Chemistry, Technical University of Lodz, 90-924 Łódz, Poland
c Department of Chemistry and Biochemistry, Ludwig Maximilians University, Butenandtstr. 5-13 (D), D-81377 Munich, Germany
d Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland
e Medical University of Lodz, Faculty of Pharmacy, Department of Cosmetic Raw Materials Chemistry, 90-151 Lodz, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
1-Benzothiazol-2-yl-3,5-dimethyl-1H-pyrazole (1a) and 1-benzothiazol-2-yl-5-(2-hydroxyphenyl)-3-
methyl-1H-pyrazole-4-carboxylic acid methyl ester (1b) were reacted with the hexahydrates of cobalt(II)
chloride, cobalt(II) nitrate and cobalt(II) perchlorate to give the corresponding complexes 2a–4a and 2b–
5b, respectively. Obtained compounds differ in coordination spheres of central atoms. The complex 2a
includes a fivefold coordinated cobalt(II) ion, whereas 3a shows a distorted octahedral configuration
around the cobalt(II) ion. All complexes were characterised by FTIR spectroscopy, MS and elemental anal-
ysis. The X-ray structures of 2a, 3a and 5b complexes were also solved. The cytotoxic properties of the
ligand 1a and both series of Co(II) complexes were examined on human leukemia NALM-6 and HL-60
cells and melanoma WM-115 cells. The ligands, were found to have very low cytotoxicity. Complex 3b
Received 23 October 2009
Received in revised form 22 February 2010
Accepted 3 March 2010
Available online 12 March 2010
Keywords:
Synthesis of cobalt(II) complexes
Cyclic voltammetry
Cytotoxicity
exhibited the highest cytotoxic activity with IC50 values in the range of 6.9–17.1
cell lines.
lM for three examined
X-ray structures
Ó 2010 Elsevier B.V. All rights reserved.
1. Introduction
agents [13]. The thiosemicarbazones complexes of cobalt(II) showed
moderate antibacterial activity against bacteria such as Escherichia
coli and Salmonella typhi and have been examined for antifungal
activity against Aspergillus niger and Candida albicans [14]. Co(II)
with Schiff bases containing the –N@C–C@N– moiety derived from
4-amino-5-sulfanyl-1,2,4-triazoles exhibit antibacterial and anti-
fungal properties [15]. Co(II) with pyrazole derivatives showed
activity against the fungi Alternaria alternata and Macrophomina
phaseoli [16]. There are also examples of cobalt(II) Schiff-based
complexes with antitumour [17] and catalytic oxidation activity
[18,19].
Cobalt(III) compounds have also been investigated for their bio-
logical activity and examined especially as tumour-selective cyto-
toxic agents because of their redox properties [20–23]. Nitrogen-
based complexes of cobalt(III) with nitrogen mustards or Schiff
bases have been investigated as promising antitumour agents
namely, hypoxia-activated prodrugs [24–32].
For many years we have been investigating the synthesis and
cytotoxic activity of metalions-complexes with pyrazoles [1–4].
These five-membered heterocyclic compounds possess promising
pharmacological, agrochemical and analytical applications [5].
The pyrazole-containing derivatives have been used as ligands
in the formation of transition-metal complexes. The antitumor
activity of these complexes is comparable with that of cisplatin
[6–9].
The increased interest in ligands containing nitrogen and/or sul-
fur and their Co(II) complexes is raised by the potential biological
activity of these compounds. Many reports described activity of co-
balt(II) complexes in many classes of nitrogen donors [10–12]. The
complexes of imidiazoles, benzimidazoles-derivatives and related
ligands with cobalt(II) have been used as effective antibacterial
This paper is a part of our research project of systematically
investigating metal(II) ions-complexes with N,N- or N,S-ligands.
Here we present the synthesis, X-ray structures of Co(II) com-
plexes, electrochemical properties and cytotoxic data of the free li-
gands and their complexes.
* Corresponding author at: Collegium Medicum in Bydgoszcz, Nicholaus Coper-
nicus University in Torun, Faculty of Pharmacy, Department of Inorganic and
Analytical Chemistry, 85-094 Bydgoszcz, Poland.
E-mail address: elzbieta.budzisz@umed.lodz.pl (E. Budzisz).
0020-1693/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2010.03.011

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M. Sobiesiak et al. / Inorganica Chimica Acta 363 (2010) 2171–2179
(495.19 g/mol): C, 46.07; H, 3.05; N, 8.48. Found: C, 45.95; H,
2.68; N, 8.35%.
2. Experimental
2.1. Materials
2.2.3. Synthesis of aqua-(1-benzothiazol-2-yl-3,5-dimethyl-1H-
pyrazole-N2,N30)-(nitrato-O,O0)-nitrato-O-cobalt(II)
(Co(1a)(NO3)2ꢁH2O) (3a)
All substances were used without further purification. The
hexahydrates of cobalt(II) chloride, cobalt(II) perchlorate and co-
balt(II) nitrate were purchased from Aldrich. CDCl3 and DMSO-d6
solvents for NMR spectroscopy were obtained from Dr. Glaser
AG, Basel. Solvents for synthesis (acetonitrile, dichloromethane,
diethyl ether, ethanol, ethyl acetate, methanol) were reagent grade
or better and were dried according to standard protocols [33]. The
melting points were determined using a Buechi Melting-Point B-
540 apparatus and they are uncorrected. The IR spectra were re-
corded on a FTIR-8400S Shimadzu Spectrophotometer in KBr. For
the new compounds, satisfactory elemental analyses were ob-
tained using a PerkinElmer PE 2400 CHNS analyser. The conduc-
tance of the metal complexes was determined in DMSO on an
Elmetron CPC-501 conductometer. The Shimadzu UV-2501 PC
(UV–Vis) study was carried out to verify the stability of complexes
in 10ꢀ3 M DMSO in 0.01 M phosphate buffer (pH 7.0) containing
0.9% NaCl (PBS) solution. The MS-FAB data were determined on
Finnigan MAT 95 mass spectrometer (NBA, Cs+ gun operating at
13 keV). The ligands: 1-benzothiazol-2-yl-3,5-dimethyl-1H-pyra-
zole [34] (1a) and 1-benzothiazol-2-yl-5-(2-hydroxyphenyl)-3-
methyl-1H-pyrazole-4-carboxylic acid methyl ester [35] (1b) were
prepared according to published methods.
Cobalt(II) nitrate Co(NO3)2ꢁ6H2O (43.7 mg, 0.15 mmol) was dis-
solved in 2 ml methanol and was added dropwise at room temper-
ature to a stirred solution of ligand 1a (34.4 mg, 0.15 mmol) in
CH2Cl2 (10 ml). The reaction solution was stirred and refluxed for
72 h and then filtered. The filtrate was kept at room temperature
by slow evaporation to diethyl ether, and after 3 weeks, red crys-
tals of 3a were obtained. Yield: 27.1 mg (42%), m.p.: 233.0–
234.2 °C. FTIR (KBr cmꢀ1):
1577, 1520;
m(O–H) 3334; m(C–CH3) 2928; m(C@N)
m
(NO3ꢀ) 1383, 812. MS-FAB (m/z): 415 (4%) Co(1a)
(NO3)2, 305 (10%) [Co(1a)(H2O)]2+, 230 (100%) 1a. Anal. Calc. for
C12H11N5SCoO6ꢁH2O (3a) (430.26 g/mol): C, 33.50; H, 3.04; N,
16.28. Found: C, 33.39; H, 3.18; N, 16.49%.
2.2.4. Synthesis of 1-benzothiazol-2-yl-5-(2-hydroxyphenyl)-3-
methyl-4-methoxycarbonyl-1-H-pyrazole-N2,N30)-dinitrato-O,O0-
cobalt(II) (Co(1b)(NO3)2) (3b)
Cobalt(II) nitrate Co(NO3)2ꢁ6H2O (30.0 mg, 0.1 mmol) was
added at room temperature to a stirred solution of ligand 1b
(37.9 mg, 0.1 mmol) in CH2Cl2 (10 ml) 1b. The reaction solution
was stirred for 24 h and was kept at room temperature by slow
evaporation to diethyl ether, and after 2 weeks, pink crystals of
3b were obtained. Yield: 23.0 mg (51%), m.p.: 250 °C dec. FTIR
2.2. Synthesis of the complexes
(KBr cmꢀ1):
m
m(O–H) 3424; m(C–CH3) 2977; m(C@N) 1563, 1515;
Caution! Perchlorate salts are potentially explosive and were han-
dled only in small quantities with care.
(NO3) 1382, 831. MS-FAB (m/z): 486 (7%) [Co(1b)NO3]+, 424
(35%) [Co(1b)]2+, 366 (100%) 1b. Anal. Calc. for C19H15N3O3SCo
(NO3)2ꢁH2O (3b) (548.29 g/mol): C, 42.43; H, 3.61. Found: C,
41.62; H, 3.18%.
2.2.1. Synthesis of bis{(l2-chlorido) (1-benzothiazol-2-yl-3,5-
dimethyl-1H-pyrazole-N2,N30)-dichlorido-cobalt(II)} (Co2(
l-Cl)2
(1a)2Cl2) (2a)
2.2.5. Synthesis of [bis(1-benzothiazol-2-yl-3,5-dimethyl-1H-
Cobalt(II) chloride CoCl2ꢁ6H2O (59.5 mg, 0.25 mmol) was
dissolved in 2 ml methanol and was added dropwise at room
temperature to a stirred solution of ligand 1-benzothiazol-2-yl-
3,5-dimethyl-1H-pyrazole (1a 57.3 mg, 0.25 mmol) in ethyl acetate
(10 ml). The stirring was continued for another hour at room tem-
perature and the reaction mixture was left standing overnight. A
blue micro-crystalline product was obtained, filtered off and dried.
Blue crystals of 2a were obtained after a few days by recrystallising
the precipitated product from acetonitrile solution by slow evapo-
ration to diethyl ether. Yield: 54.8 mg (65%), m.p.: 303.5–305.1 °C.
pyrazole-N2,N30)-cobalt(II)] diperchlorate (Co(1a)2(ClO4)2) (4a)
Cobalt perchlorate Co(ClO4)2ꢁ6H2O (73.2 mg, 0.2 mmol) was
dissolved in 1 ml methanol and was added dropwise at room tem-
perature to a stirred solution of ligand 1a (91.7 mg, 0.4 mmol) in
ethyl acetate (20 ml). The reaction solution was stirred for 5 h
and then was kept at room temperature by slow evaporation to
diethyl ether, and after one week, pink crystals of 4a were ob-
tained. Yield: 119 mg (82%), m.p.: 314.1–314.4 °C. FTIR (KBr
cmꢀ1):
m
m
(O–H) 3442;
m
(C–CH3) 3099;
m
(C@N) 1580, 1517;
(ClO4ꢀ) 1127, 616. MS-FAB (m/z): 618 (4%) [Co(1a)2]2+ClO4
,
ꢀ
FTIR (KBr cmꢀ1):
m(C–CH3) 2915; m(C@N) 1574, 1521. MS-FAB
517 (4%) [Co(1a)2]2+, 288 (8%) [Co(1a)]2+, 230 (38%) 1a. Anal. Calc.
for C24H22N6S2Co(ClO4)2ꢁ1/2H2O (4a) (725.44 g/mol): C, 40.23; H,
3.09; N, 11.73. Found: C, 39.73; H, 3.19; N, 11.58%.
(m/z): 288 (15%) [Co(1a)H]+, 230 (100%) 1a. Anal. Calc. for
C12H11N3SCoCl2 (2a) (359.13 g/mol): C, 40.13; H, 3.09; N, 11.70.
Found: C, 40.29; H, 3.21; N, 11.56%.
2.2.2. Synthesis of 1-benzothiazol-2-yl-5-(2-hydroxyphenyl)-3-
methyl-4-methoxycarbonyl-1H-pyrazole-N2,N30-dichlorido-cobalt(II)
(Co(1b)Cl2) (2b)
2.2.6. Synthesis of [bis(1-benzothiazol-2-yl-5-(2-hydroxyphenyl)-3-
methyl-4-methoxycarbonyl-1H-pyrazole-N2,N30)-cobalt(II)]
diperchlorate (Co(2b)2(ClO4)2ꢁ2H2O) (4b)
Cobalt(II) chloride CoCl2ꢁ6H2O (48.4 mg, 0.2 mmol) was
dissolved in 1 ml methanol and was added dropwise at room tem-
perature to a stirred solution of ligand 1-benzothiazol-2-yl-5-(2-
hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboxylic acid methyl
ester (1b 73.6 mg, 0.2 mmol) in ethyl acetate (10 ml). The stirring
was continued for another 3 h at room temperature and the reac-
tion mixture was left standing overnight. Violet micro-crystalline
product 2b was obtained, filtered off and dried. Yield: 69.8 mg
Cobalt perchlorate Co(ClO4)2ꢁ6H2O (20.2 mg, 0.055 mmol) was
dissolved in 1 ml methanol and was added at room temperature
to a stirred solution of ligand 1b (40.1 mg, 0.11 mmol) in ethyl ace-
tate (10 ml). The reaction solution was stirred and refluxed for 24 h
and then was kept at room temperature by slow evaporation to
diethyl ether, and after one week, brown-orange crystals of 4b
were obtained. Yield: 50.1 mg (92%), m.p.: 254–255.5 °C. FTIR
(KBr cmꢀ1):
(C@C) 1569; m
(ClO4ꢀ) 1116, 265. MS-FAB (m/z): 793.4 (35%)
m(O–H) 3401; m(C@O) 1710; m(C@N) 1612, 1514;
(72%), m.p.: 308.0–308.4 °C. FTIR (KBr cmꢀ1):
m
(OH) 3278;
m
(C–
m
CH3) 2953;
m
(C@O) 1718,
m(C@N) 1612, 1519,
m(C–O–C) 1114,
[Co(1b)2]2+, 524 (3%) [Co(1b)ClO4], 428 (100%) [Co(1b)]2+, 366
(25%) 1b. Anal. Calc. for C38H30N6O6S2Co(ClO4)2ꢁ2H2O (4b)
(1024.56 g/mol): C, 44.23; H, 4.0. Found: C, 44.55; H, 3.64%.
1099. MS-FAB (m/z): 458.9 (46%) [Co(1b)Cl]+, 423 (18%)
[Co(1b)]2+, 366 (24%) 1b. Anal. Calc. for C19H15N3O3SCoCl2 (2b)

M. Sobiesiak et al. / Inorganica Chimica Acta 363 (2010) 2171–2179
2173
2.2.7. Synthesis of acetonitrile-(1-benzothiazol-2-yl-5-
2.5.2. Cytotoxicity assay by MTT
(2-hydroxyphenyl)-3-methyl-4-methoxycarbonyl-1H-pyrazole-
The cytotoxicity of ligand 1a, the complexes 2a–4a, as well as
2b–4b carboplatin and cisplatin were determined by the MTT [3-
(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Sig-
ma, USA] assay as described [40]. Stock solutions of the analysed
compounds were freshly prepared in DMSO and diluted with com-
plete culture medium to obtain a concentration range from 10ꢀ7 to
10ꢀ3 M. Cells were exposed to the test compounds for 46 h, then
MTT reagent was added and incubation was continued for 2 h.
After incubation, MTT-formazan crystals were dissolved in 20%
SDS and 50% DMF at pH 4.7 and absorbance was read at 562 nm
on an ELISA-plate reader (ELX 800, Bio-Tek, USA). The values of
IC50 (the concentration of test compound required to reduce the
cells’ survival fraction to 50% of the control) were calculated from
concentration–response curves and used as a measure of cellular
sensitivity to a given treatment. As a control, cultured cells were
grown in the absence of drugs. Data points represent means from
2 to 4 experiments, each performed at 5 repeats S.D.
N2,N30)-dichlorido-cobalt(II) (Co(2b)Cl2CH3CN) (5b)
Green crystals of 5b were obtained after a few days by re-crys-
tallizing 25 mg of the precipitated product 2b from the acetonitrile
solution by slow evaporation to diethyl ether. Yield: 13.5 mg (54%),
m.p.: 320.5–321.0 °C. FTIR (KBr cmꢀ1):
m
(OH) 3423,
(C–O–C) 1113, 1098. MS-FAB
(m/z): 534 (M, 7%), 459 (57%) [Co(1b)Cl]+, 424 (22%) [Co(1b)]2+
m(C–CH3) 2950;
m
(C@O) 1720, m(C@N) 1615, 1520; m
,
366 (21%) 1b. Anal. Calc. for C19H15N3O3SCoCl2ꢁCH3CN (5b)
(536.24 g/mol): C, 47.76; H, 3.49. Found: C, 47.04; H, 3.38%.
2.3. X-ray structure determinations of 2a, 3a and 5a
All measurements of the crystal 2a were performed on Kuma 4-
CCD k-axis diffractometer with graphite-monochromated Mo K
a
radiation at room temperature. The crystals were positioned at
62 mm from the KM4-CCD camera, 496 frames were measured at
1.5 intervals with a counting time of 25 s. The data were corrected
for Lorentz and polarisation effects. Multi-scan absorption correc-
tion was applied. Data reduction and analysis were carried out
with the Kuma Diffraction programs [UNIL IC & KUMA (2000), Cry-
sAlis CCD, ver. 1.163; Kuma Diffraction Instruments GmbH, Wro-
cław, Poland]. The structures were solved by direct methods [36]
and refined using SHELXL 93 [37]. The full-matrix least-squares
refinement was based on F2 and applied anisotropic temperature
factors for all non-H atoms; positions of all H atoms were found
from electron-density maps and were refined in riding model with
the isotropic displacement parameters of 1.5 times the respective
Ueq values for the parent atoms. Atomic scattering factors were ob-
tained from SHELXL. X-ray data for 3a and 5b were collected at 200 K
3. Results and discussion
3.1. Chemistry
Looking for effective antitumour agents, we have decided to
synthesise Co(II) complexes. In our previous studies similar com-
pounds were shown to possess chelating properties towards many
ions [41,42].
For our project we chose the two similar ligands presented in
Fig. 1. We were interested in how the ligands’ structure influences
the cytotoxic activity of the complexes. Six cobalt(II) complexes
with 1-benzothiazol-2-yl-3,5-dimethyl-1H-pyrazole (1a) and 1-
benzothiazol-2-yl-5-(2-hydroxyphenyl)-3-methyl-1H-pyrazole-4-
carboxylic acid methyl ester (1b) as ligands were synthesised.
Three Co(II) complexes with 1a were obtained by alternatives to
the Arali and Zhang method (see Scheme 1) [35,43]. Those authors
have shown the synthesis and antibacterial studies of 1-ben-
zothiazol-2-yl-3,5-dimethyl-1H-pyrazole complexes of cobalt(II),
nickel(II) and copper(II). Unfortunately, the authors had not re-
ported important data such as the reaction yield or melting points
of compounds. We also would have been interested in the electro-
chemical properties, X-ray structure and cytotoxic activity of syn-
thesised Co(II) complexes.
As a part of our systematic investigation we presented the syn-
thesis of new chelating ligand 1-benzothiazol-2-yl-5-(2-hydroxy-
phenyl)-3-methyl-1H-pyrazole-4-carboxylic acid methyl ester
(1b) and its complexes with platinum(II), palladium(II) and cop-
per(II) ions. Cytotoxicity studies showed the high effectiveness of
Cu(II) complexes for skin melanoma WM-115 cells. The Cu(II)
and Pt(II) complexes were chosen for BAX and P53 gene expression
study [35].
with Mo Ka radiation (k = 0.71073 Å) with a Nonius KappaCCD dif-
fractometer equipped with a rotating anode generator. The struc-
ture was solved by direct methods with SIR97 [38] and refined
with SHELXL-97 by full-matrix least-squares on F2 [39].
2.4. Redox properties
The electrochemical properties of these complexes have been
studied by cyclic voltammetry in DMF solution. Voltammetric
measurements were made with the aid of a PGSTAT12 AUTOLAB
electrochemical analyser. Three electrodes were utilised in this
system, a glassy carbon working electrode (GCE), a platinum-wire
auxiliary electrode and silver wire in contact with 0.1 M AgNO3 in
an ACN reference electrode. The GCE with 3.0 mm diameter was
manually cleaned with 1 lm alumina polish prior to each scan.
All solutions were deaerated for 10 min, prior to measurements
with pure argon. A blanket atmosphere of argon was maintained
over the solution during measurements. The potentials were mea-
sured in 0.2 M [nBu4N][BF4]/DMF as the supporting electrolyte,
The ligand 1b in the reactions with cobalt(II) chloride, cobalt(II)
nitrate and cobalt(II) perchlorate hexahydrate created the solid
complexes 2b–5b (Scheme 1). Two complexes (2b, 3b) were
formed in molar ratio 1:1 in ethyl acetate/methanol and
using the [Fe(
standard.
g
5-(C5H5)2] in DMF (E1/2 = +0.72 V) as the internal
2.5. Biological assays
OH
2.5.1. Cell cultures
COOCH3
H3C
Human skin melanoma WM-115 cells as well as human leuke-
mia promyelocytic HL-60 and lymphoblastic NALM-6 cells were
used. Leukemia cells were cultured in RPMI 1640 medium (Invitro-
gen, UK) supplemented with 10% fetal bovine serum and antibiot-
S
S
N
N
CH3
N
CH3
N
N
N
ics (100 lg/ml streptomycin and 100 U/ml penicillin). For
melanoma WM-115 cells, Dulbecco’s minimal-essential medium
(DMEM) was used instead of RPMI 1640. Cells were grown in
37 °C in a humidified atmosphere of 5% CO2 in air.
b
a
Fig. 1. The structure of ligands 1a and 1b.

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M. Sobiesiak et al. / Inorganica Chimica Acta 363 (2010) 2171–2179
OH
CO2CH3
N
S
CH3
Cl
N
N
Co
Cl
5b
NCAc
cryst. AcCN
H
OH
CH3
CO2CH3
H3C
Cl
Cl
N
S
N
N
N
N
S
Co Co
CH3
N
N
S
N
N
Cl
2a
CH3
Co
Cl
Cl
H3C
Cl
H
2b
1a,1b, CoCl2 x 6H2O
H
1
H
R
N
R
1 : 1
O
O
N
S
O
H3C
O
O
O
CH3
N
1a, Co(NO3)2 x 6H2O
Co
N
H
N
N
O
1 : 1
N
N
H3C
Co(1b)(NO3)2
1a, 1b
S
3a
3b
2+
1a R = CH3, R1 = H
1b R = 2'-OH-Ph, R1 = CO2CH3
1
R
R
N
S
CH3
N
N
Co
1 : 2
-
N
2 x ClO4
N
1b, Co(ClO4)2 x 6H2O
H3C
S
N
1
R
R
4a, b
Scheme 1. Synthesis of Co(II) complexes 2a, 2b, 3a, 3b, 4a, 4b and 5b.
dichloromethane solution, respectively. Ligand 1b with cobalt(II)
perchlorate hexahydrate in ethyl acetate solution formed the com-
plex 4b in molar ratio of 2:1. Single crystals of 3b and 4b have been
obtained by slow diffusion of diethyl ether. Recrystallisation of the
complex 2b by the slow diffusion of diethyl ether into acetonitrile
gave the cobalt(II) complex 5b. We have been interested in electro-
chemical properties, X-ray structure and cytotoxic activity of
synthesised new Co(II) complexes and which substituents in 4-
or 5-position of the pyrazole ligands influence the cytotoxity of
their Co(II) complexes.
3a, 3b in DMSO suggest that they are non-electrolyte but indicat-
ing solvation of the complexes. Complexes 4a and 4b are electro-
lytes in 10ꢀ3 M DMSO with values 97.4 and 95.0 (ohmꢀ1 cm2
molꢀ1), respectively. Therefore, the perchlorate anion is outside
the metal coordination sphere.
The results of the UV–Vis study are shown in Table 1. Absorp-
tion spectra of DMSO/PBS solution complexes (10ꢀ6 do 10ꢀ4 M)
were recorded in time intervals: t = 0 h, t = 1 h, t = 2 h, t = 24 h,
t = 48 h. UV–Vis absorption spectra of ligands and their complexes
showed characteristic peaks in the region of 250–350 nm. The
absorption wavelength of complexes exhibited blue shifts com-
pared with the ligands. The kmax (nm) values of only two Co(II)
The conductivity behaviour of complexes in DMSO was exam-
ined. The low conductivity values observed for complexes 2a, 2b,

M. Sobiesiak et al. / Inorganica Chimica Acta 363 (2010) 2171–2179
2175
Table 1
bonds in all obtained complexes were being created by nitrogen
atoms and not by sulfur atoms. Comparative analysis of the infra-
red spectra of the complexes and the metal-free ligand has re-
vealed that the absorption bands characteristic for the stretching
vibrations of pyrazol C@N group were shifted from 1600 cmꢀ1 for
ligand 1a to 1574, 1577, 1780 cmꢀ1 for complexes 2a, 3a, and 4a
as a consequence of the N coordination. The intensive, broad band
in the 3000–3600 cmꢀ1 region is exhibited by a water molecule en-
closed in 2a. The band at 1715 cmꢀ1 in the spectra of ligand 1b,
which has been assigned to the C@O vibrations, is now shifted to
higher energies for the complexes 2b, 3b, 5b (1722–1718 cmꢀ1).
The IR-bands at 3416–3056 cmꢀ1 in the spectra of the ligand 1b
and complexes 3b–5b are assigned to the hydroxy group of the
phenyl ring. The characteristic bands at 3103–2915 cmꢀ1 of the
methyl group of the ligand 2b and its complexes 3b–5b are as-
signed to C–H vibration. The presence of two bands between
1300–1400 cmꢀ1 (very strong) and 800–860 cmꢀ1 (medium)
UV–Vis data (kmax) of compounds (1a,b–4a,b) in DMSO/PBS solution during 48 h.
Time (h)
0
1
2
24
48
Compound
kmax (nm)
1a
2a
3a
4a
1b
2b
3b
4b
287
289
294
296
292
297
296
295
287
290
294
296
292
297
296
295
287
288
293
296
292
297
296
295
287
288
295
296
292
297
296
295
287
290
297
296
292
297
296
295
compounds 2a, 3a were slightly changed during 48 h, meaning that
the examined complexes were stable in solution.
ꢀ
3.1.1. MS-FAB
shows that 3a and 3b include NO3 ions. The bands observed at
1127, 617 and 1116, 626 cmꢀ1 in the spectra of 4a and 4b are
characteristic for non-coordinated perchlorate ions [44]. These
observations correspond with crystallographic data obtained from
X-ray structure analysis of these complexes.
For valuable structural information Co(II) complexes 2a,b–4a,b
and 5b were investigated by mass spectrometric measurement.
Table 2 contains structurally informative molecular and fragment
ions of cobalt(II) complexes. For all compounds in series 2a–4a par-
ent pick of complexes have not been observed in FAB-MS spectra.
However, during the MS analysis the signals corresponding to their
fragmentation ions CoL have been present. Moreover, for com-
pound 2a in FAB-MS spectra the following signals have been
found: L2Co2Cl (M+ꢀ683), L2Co2Cl2 (M+ꢀ647), CoLCl (M+ꢀ323).
This data are in good agreement with crystallographic study which
suggests the dimeric structure for compound 2a.
3.2. X-ray structure analysis
X-ray structure analyses of the complexes 2a, 3a and 5b were
conducted. All details of the X-ray-structure analysis are summa-
rised in Table 3 and selected geometrical parameters are shown
in Table 4.
The FAB-MS analysis of compound 3a has exhibited suitable
+
fragmentation ion CoLNO3 (M+ꢀ350). For the compound 4a two
3.2.1. Structural discussion of 2a
characteristic signals for this structure have been observed: CoL2
(M+ꢀ517) and CoL2ClO4 (M++2Hꢀ618). The molecular ion peak of
complex 5b was found at (m/z) 534 indicating that complex corre-
sponding to CoLCl2 with one acetonitrile molecule. FAB-MS spectra
of all complexes presented ion peak corresponded to ligand. For all
complexes series b it was main fragment with m/z of 366 (100%).
The molecular peaks for 3b and 4b complexes corresponding to
compounds with metal bonded to two ligand molecules at (m/z)
788 and 793. Additionally, a mass peaks of CoLCl (M+ꢀ458), CoL-
NO3 (M+ꢀ486), CoLClO4 (M+ꢀ524), ions were observed in the mass
spectra of coordination 2b, 3b and 4b, respectively.
As shown in the crystallographic structure of the complex in
Fig. 2a two cobalt centres are linked via two chlorido bridges form-
ing centrosymmetric dimeric units. The third chlorido ligand as
well as the bidentate pyrazole 1a completes the five-coordinated
environment around the cobalt atom. The metal ion is in distorted
trigonal-bipyramidal coordination. The axial bond angle N1–Co–
Cl2A is 167.23(5)°, while the equatorial bond angles around the
central Co atom are 118.28(3), 118.30(5), 121.75(5). The Co atom
is 0.167 Å above the plane defined by N3, Cl1A and Cl2, towards
the Cl2A atom. Hence, for a complete geometry description, the
two Co–N and three Co–Cl distances are essential. The Co–N1
and Co–N3 distances of 2.1570(18) and 2.0834(17), respectively,
are typical within pyrazine-like ligands. The Co–Cl distances are
about 0.3 Å longer than Co–N ones. For 4 four structurally similar
Co complexes found in the Cambridge Crystallographic Database
(CSD, version 1.10 of Nov 2008) [45,46] the average value of Co–
N distance is 2.064 Å, while the average Co–Cl distance equals
2.3872 Å.
The presented above data are in good agreement with results
obtained by elemental analysis, therefore confirm proposed by X-
ray spectroscopy structure of investigated complexes.
3.1.2. IR analysis
The band in the 1512–1521 cmꢀ1 region of the complexes 2a,
2b, 2a, 3b, 4a, 4b, 5b has been assigned to C@N of the benzothia-
zole moiety. A shift of absorption bands characteristic to the vibra-
tions of C@S group in region 580–700 cmꢀ1 was absent in obtained
spectra, indicating that the sulfur atom is not involved in coordina-
tion to cobalt(II). The infrared spectra showed that ligand–metal
The molecular packing is depicted in Fig. 2b. The aromatic moi-
eties form a stack down the c-axis with a distance of about 3.657 Å.
No hydrogen bonds were identified in the discussed structure.
3.2.2. Structural discussion of 3a
Complex 3a contains four different ligands around the distorted
octahedral Co(II) centre; they are the N,N0-chelating diimine ligand
1a, one O-monodentate and one O,O0-bidentate nitrato ligand and
one aqua ligand (Fig. 3a). As in 2a, the functionalised diimine li-
gand 1a is again planar, the most deviation from planarity is given
with the torsion angle N1–C1–N2–N3 = 3.7(3)° caused by its che-
lating function from different directions with different neighbours.
The bonds Co–N (Co–N1 2.1266(18), Co–N3 2.0969(18) Å) are
also slightly different but within the range of those in 2a. The
four Co–O bonds differ more. Whereas Co–O4 (2.0591(17) Å)
of the aqua ligand and Co–O7 (2.0766(17) Å) of the nitrato-O
ligand are the shortest, both Co–O1 (2.2471(18) Å) and Co–O2
Table 2
MS data (m/z) of complexes 2a,b–4a,b, 5b.
Compound
Molecular ions
Fragment ions
2a
3a
4a
2b
3b
4b
5b
230.1, 288.4, 683, 647
230.1, 305.1, 415.3
230.1, 288.2, 618.2, 517.5
366.2, 423.4, 458.9,
788.0, 486.1, 424.0, 366.0
793.4, 524.1, 428.2, 366.1
459.0, 424.2, 366.1
534

2176
M. Sobiesiak et al. / Inorganica Chimica Acta 363 (2010) 2171–2179
Table 3
Crystal data and details of the structure determinations of 2a, 3a and 5b.
2a
3a
5ba
Net formula
C12H11N3SCo
C12H13N5O7SCo
430.26
C22H19.75Cl2CoN4.50O3.13
559.155
0.16 ꢂ 0.10 ꢂ 0.02
200(2)
S
Mr/g (molꢀ1
Crystal size (mm)
T (K)
)
359.13
0.2 ꢂ 0.15 ꢂ 0.16
296(2)
0.15 ꢂ 0.14 ꢂ 0.08
200(2)
Diffractometer
Crystal system
Space group
a (Å)
b (Å)
c (Å)
Kuma 4-CCD
monoclinic
P21/n
8.2185(3)
15.7480(6)
10.9946(4)
90
101.982(1)
90
1391.97(9)
4
Kappa CCD
triclinic
Kappa CCD
monoclinic
C2/c
31.5577(8)
9.6036(3)
21.6625(5)
90
131.8696(14)
90
4888.9(2)
8
ꢀ
P1
8.6816(3)
8.7267(2)
12.2007(4)
86.688(2)
69.4420(17)
70.1178(17)
811.90(4)
2
a
(°)
b (°)
c
(°)
V (Å3)
Z
Calculated density (g cmꢀ3
)
1.714
1.753
1.76
1.235
1.51938(6)
1.04
l
(mmꢀ1
)
Absorption correction
Reflections measured
Rint
multi-scan
22888
0.028
0.0132
2.29–25.00
2175
0.0342, 0.6987
geom
none
7025
none
17300
0.0514
0.0465
3.36–26.04
3715
0.0284, 3.4552
mixed
4808
316
0.0297
0.0464
3.58–27.48
2843
0.0260, 0.3865
mixed
Mean
r(I)/I
h Range
Observed reflections
x, y (weighting schemes)
Hydrogen refinement
Reflections in refinement
Parameters
2449
174
3702
243
Restraints
0
2
0
R(Fobs
)
0.032
0.0655
1.08
0.0342
0.0778
1.055
0.0331
0.0781
1.034
Rw(F2)
S
Shift/errormax
0
0.001
0.354/ꢀ0.35
0.001
0.323/ꢀ0.342
Maximum/minimum electron-density (e Åꢀ3
)
0.364/ꢀ0.187
a
Per formula unit not coordinated: 0.125 H2O and 0.5 CH3CN.
Table 4
Selected geometrical parameters of complexes 2a, 3a and 5b.
2a
3a
Bond lengths (Å)
5b
Bond lengths (Å)
Bond angles (°)
Bond angles (°)
Bond lengths (Å)
Bond angles (°)
Co–N1
Co–N3
Co–Cl1
Co–Cl2
Co–Cl2A*
Co–CoA*
2.1570(18)
Cl1–Co–Cl2
N1–Co–N3
118.28(3)
75.99(7)
167.23(5)
99.53(5)
118.30(5)
94.25(5)
121.75(5)
287.27(5)
99.53(5)
98.37(2)
85.03(2)
Co–N1
Co–N3
Co–O1
Co–O2
Co–O4
Co–O7
O1–N4
O2–N4
O3–N4
O4–N5
O5–N5
O6–N5
2.1266(18)
N1–Co–N3
O1–Co–O2
O1–Co–N3
O1–Co–N1
O1–Co–O4
O2–Co–O4
O2–Co–O7
O2–Co–N3
N3–Co–O4
N3–Co–O7
N1–Co–O7
N1–Co–O4
76.84(7)
Co–Cl1
Co–Cl2
Co–N1
Co–N3
Co–N4
N4–C20
C20–C21
2.3218(7)
2.2671(12)
2.1507(18)
2.123(2)
2.102(2)
1.135(3)
Cl1–Co–Cl2
Cl1–Co–N1
Cl1–Co–N3
Cl1–Co–N
Cl2–Co–N1
Cl2–Co–N3
Cl2–Co–N4
N1–Co–N3
N1–Co–N4
N3–Co–N4
Co–N4–C20
119.69(4)
87.60(5)
120.81(7)
490.31(6)
94.70(7)
117.93(7)
96.79(8)
75.35(8)
2.0834(17)
2.2684(7)
2.3581(7)
2.4166(7)
3.5190(8)
2.0969(18)
2.2471(18)
2.1634(17)
2.0591(17)
2.1266(18)
1.273(2)
1.260(2)
1.223(3)
1.271(2)
1.235(3)
58.15(6)
91.55(6)
95.38(7)
174.68(6)
117.67(7)
90.52(7)
146.51(7)
93.31(7)
102.41(7)
177.97(7)
87.84(7)
Cl2A–Co–N1
Cl2A–Co–N3
N3–Co–Cl1
N1–Co–Cl1
N3–Co–Cl2
N1–Co–Cl
1.449(4)
N3–Co–Cl2A*
Cl1–Co–Cl2A*
Cl2–Co–Cl2A*
167.78(11)
95.51(9)
176.6(2)
1.241(2)
Torsion angles (°)
N1–C7–N2–N3
N1–Co–N3–N2
4.1(4)
1.9(11)
N1–C1–N2–N3
N1–Co–N3–N2
3.7(3)
1.8(13)
N1–Co–N3–N2
N1–C1–N2–N3
ꢀ12.97(17)
ꢀ13.4(3)
Hydrogen bridges
O7–H71–O635 0.844(10), 1.907(12),
2.739(2), 168(3)
O1ꢁ ꢁ ꢁH1ꢁ ꢁ ꢁCl1i 0.78(3), 2.33(3), 3.102(2),
175(4)
(i = 1/2 ꢀ x, 1/2 + y, 1/2 ꢀ z)
O7–H72–O136 0.827(10), 2.261(16),
3.020(2), 153(3)
C-bonded H: constr; O-bonded H: O–H fixed to 0.84 Å, U(H) = 1.5 ꢂ U(O).
*
Cl2A and CoA denotes the symmetry equivalents of atoms Cl2 and Co.
(2.1634(17) Å) of the nitrato O,O0 ligand are significantly longer
and, additionally, they are not equal. As expected, the nitrato li-
gands are planar and the N–O bond lengths lie in the range of
1.223(3) (N4–O3) to 1.271(2) Å (N5–O4) depending on whether
coordinated or not. Of the two of the bite-angles, that of O1–Co–
O2 = 58.15(6)° is much smaller than N1–Co–N3 (76.84(7)°) (2a:
75.97(6)°) because of its four-membered ring situation. The mono-
dentate nitrato ligand is slightly bent off the molecular plane
defined by O1, O2, O4 and N3 with the torsion angle Co–O4–N5–
O5 = ꢀ8.5(2)° (Fig. 3b).

M. Sobiesiak et al. / Inorganica Chimica Acta 363 (2010) 2171–2179
2177
Fig. 2a. An ORTEP drawing of 2a with atom numbering. The non-hydrogen atoms
are shown with 50% probability ellipsoids.
Fig. 2b. Stacking of 2a molecules down the c-axis.
Fig. 3b. Stacking of 3a molecules down the c-axis.
Fig. 3a. An ORTEP drawing of 3a with atom numbering. The non-hydrogen atoms
are shown with 50% probability ellipsoids.
Fig. 4b.
p–p-stacking in 5b within the c-axis (i = 0.5 ꢀ x, 0.5 ꢀ y, 1 ꢀ z). The non-
coordinating solvate molecules H2O and CH3CH are omitted.
the chelate system in equatorial positions (Cl1–Co–Cl2 119.69(4),
Cl1–Co–N3 120.81(7), Cl2–Co–N3 117.93(7)°) (see Fig. 4a). The
other chelating atom N1 and N4 of the coordinating CH3CN lie in
trans-axial positions (N1–Co–N4 167.78(11)°). The angles between
equatorial and apical ligands vary from 87.60(5)° (Cl1–Co–N1) to
96.79(8)° (Cl2–Co–N4) with the only exception being angle N1–
Co–N3 75.35(8)° due to its bite-angle character. The acetonitrile
Fig. 4a. An ORTEP drawing of 5b with atom numbering. The non-hydrogen atoms
are shown with 50% probability ellipsoids.
3.2.3. Structural discussion of 5b
The Co(II) centre in complex 5b shows a distorted trigonal-bipy-
ramidal configuration with two chlorido ligands and atom N3 of

2178
M. Sobiesiak et al. / Inorganica Chimica Acta 363 (2010) 2171–2179
Table 6
ligand is nearly linearly bonded (Co–N4–C20 176.6(2)°). Although
in apical position, it shows the shortest Co–N bond (Co–N4
2.102(2) Å); its counterpart, Co–N1 2.151(2) Å, however, the lon-
gest one (Co–N3 2.123(2) Å). Both bond lengths Co–Cl differ some-
what (Co–Cl1 2.3218(7), Co–Cl2 2.2672(2) Å), but they lie, as do
the Co–N distances, in the range of 2a and 3a. With the torsion an-
gles N1–C1–N2–N3 ꢀ13.4(3)° and N1–Co–N3–N2 ꢀ12.97(17)°, the
ligand itself, as well as the five-membered metallacycle are again
planar. In contrast to 3a with two intramolecular Oꢁ ꢁ ꢁHꢁ ꢁ ꢁO
bridges, there is an intermolecular hydrogen bridge between the
chlorido ligand Cl1 and the oxygen of the non-coordinate solvate
molecule H2O. Between the five-membered rings of the benzothi-
Cytotoxic activity
cisplatin and carboplatin to HL-60, NALM-6 and WM-115 cells.
(l
M)a of ligand 1a, 1b and their Co(II) complexes 2a,b–4a,b,
Compound
Cytotoxicity (
HL-60
l
M)a
NALM-6
WM-115
1a
368.8 18.8
>1000
367.4 22.2
74.0 12.9
44.4 5.4
7.5 0.1
9.7 0.3
6.9 0.1
7.1 0.3
8.0 0.2
0.7 0.3
0.7 0.2
743.8 76.4
55.1 8.2
69.8 2.3
54.1 7.7
77.9 8.9
8.9 0.3
88.1 3.1
20.3 3.1
18.2 4.3
422.2 50.2
1bb
2a
2b
3a
3b
4a
4b
46.3 3.8
10.2 1.7
41.6 4.6
17.1 3.0
45.4 6.4
24.6 4.0
0.8 0.1
Cisplatin
Carboplatin
azole part of 5b a p–p-stacking is observed with the shortest dis-
tances between S and C21 or C2 and Si (3.457(3) Å) (Fig. 4b).
4.3 1.3
a
IC50-concentration of a tested compound to reduce the fraction of surviving
cells to 50% of that observed in the control, non-treated cells. Mean values of IC50 (in
3.3. Cyclic voltammetry
l
M) S.D. from 2 to 4 experiments each performed in quintuple are presented.
See literature [35].
b
Electrochemical studies of cobalt(II) complexes have been done
in connection with the investigation of their biological properties.
The cyclic voltammogram of complex 2a shows two waves at
as leukemia promyelocytic HL-60 and lymphoblastic NALM-6 cells.
Cisplatin and carboplatin were used as the reference compounds.
The cells were exposed to a broad range of drug concentrations
(10ꢀ7 to 10ꢀ3 M) for 48 h and cell viability was analysed by MTT
assay. IC50 values are presented in Table 6. Metal complexes 2a–
4a and 4b exhibited rather moderate cytotoxicity to leukemia
HL-60 cells although complex 2b was more active. Relatively high
ꢀ0.110 V and ꢀ1.380 V. The peak-to-peak separation
(DEp)
amounts to 1.27 V and proportion of the anodic peak current (ipa
)
and the cathodic peak current (ipc) indicate a quasireversible pro-
cess. A representative illustration is given in Fig. S5.
The voltammogram of complex 2b shows two waves at 0.052 V
and ꢀ0.827 V (Fig. S6). The peak-to-peak separation (
DEp) amounts
cytotoxic activity with an IC50 of 6.9–9.7 lM was observed for
to 0.879 V and proportion of the anodic peak current (ipa) and the
cathodic peak current (ipc) indicate a quasireversible process. The
reduction potential of 2b is the highest of analysed complexes,
therefore peak-to-peak separation value is lowest of them.
complexes 2b, 3a, 3b, 4a, 4b in the case of lymphoblastic NALM-
6 cells. The complexes 3b and 4b exhibited higher cytotoxic activ-
ity in the case of skin melanoma WM-115 cells. The cytotoxic
effectiveness of these compounds with an IC50 of 8.9
and 20.3 M (4b) was higher or comparable to that of cisplatin
(18.2 M) and was much higher than that of carboplatin
(422.2 M). It should also be mentioned that ligands 1a and 1b
lM (3b)
The cyclic voltammograms of 3a, 3b, 4a, 4b are similar
(Figs. S7–S10). They show one reduction and one oxidation wave.
Potentials of reduction waves are in the range from ꢀ1.238 V to
ꢀ1.340 V. Potentials of oxidation waves are in the range from
l
l
l
presented low toxicity.
ꢀ0.091 V to 0.070 V. The peak-to-peak separation (DEp) of higher
than 1.180 V and proportion of the anodic peak current (ipa) and
the cathodic one (ipc) indicates a quasireversible process. All these
results are consistent with a quasireversible behaviour. These ob-
tained voltammograms exhibit one step reduction process from
Co2+ ? Co1+ which is probably stabilized by the ligand environ-
ment. This fact explains the high value of peak-to-peak separation
according to a quasireversible process.
Complex 2a shows one additional reduction peak at ꢀ2.090 V
like complex 2b at ꢀ1.953 V. Both complexes include chlorido li-
gands in the structure. The cyclic voltammograms of both ligands
1a, 1b do not exhibit any waves. The oxidation and reduction
potentials and peak-to-peak separation values of all investigated
complexes are gathered in Table 5.
4. Conclusions
We have investigated in this paper the synthesis, X-ray struc-
tures, electrochemical properties, and cytotoxic effect of cobalt(II)
complexes. Their synthesis from the hexahydrates of CoCl2,
Co(NO3)2, and Co(ClO4)2 as substrates resulted in new and different
structures. The electrochemical behaviour of analysed complexes
shows a quasireversible (DEp higher than 0.879 V) process.
Preliminary cytotoxic studies indicate that cobalt(II) complexes
with ligand 1a display acceptable, but less cytotoxic activity as
compared to cisplatin and carboplatin. Cobalt(II) complexes with
ligand 1b were found to display higher cytotoxic activity as com-
pared to 2a–4a and even as compared to that of reference com-
pounds. The complexes 3b and 4b exhibited higher cytotoxic
activity in NALM-6 and WM-115 cell lines. Therefore, these com-
plexes could serve as cobalt models for further cytotoxic studies.
The free ligand 1a presented low cytotoxicity in comparison to
1b. Both examined ligands possess the pyrazole and benzothiazole
moiety. The cytotoxity studies indicate that substituents in the 4-
or 5-position of the pyrazole molecules have an effect on their
activity.
In complexes discussed, the dihedral angles N3–N2–C1–N1
have been found close to 0°. Moreover, shortening of the N2–C1,
C1–S1 bonds and elongation of C1–N1 bond were observed. Addi-
tionally, in the octahedral complex, one of the oxygen atoms of the
NO3 group has been involved in the creation of the hydrogen bond
with the apical water molecule. The natural population analysis
has shown the charge transfer from ligands to metal centre under
the charge comparison between the free ligand and the discussed
complexes. These differences of spatial geometry and charge
3.4. Biological assays
3.4.1. Cytotoxicity studies
The cytotoxicity of ligands 1a, 1b and their Co(II) complexes
2a,b–4a,b was assayed against melanoma WM-115 cells as well
Table 5
Electrochemical oxidation potential (Epa), reduction potentials (Epc) and peak-to-peak
separation (DEp) of analysed complexes.
Compound
Epa1
Epc1
D
Ep1
Epa2
Epc2
DEp2
2a
2b
3a
3b
4a
4b
ꢀ0.110
0.052
ꢀ0.058
ꢀ0.091
0.070
ꢀ1.380
ꢀ0.827
ꢀ1.238
ꢀ1.340
ꢀ1.240
ꢀ1.330
1.270
0.879
1.180
1.249
1.240
1.310
ꢀ2.090a
ꢀ1.953a
ꢀ0.020
a
Only irreversible reduction.

M. Sobiesiak et al. / Inorganica Chimica Acta 363 (2010) 2171–2179
2179
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