Seven coordinated cobalt(II) complexes with 2,6-diacetylpyridine bis(4-acylhydrazone) ligands: Synthesis, characterization, DNA-binding and nuclease activity

Article abstract of DOI:10.1016/j.ica.2015.03.040

A new series of pentadentate 2,6-diacetylpyridine bis(4-acylhydrazone)s (H₂L¹ and H₂L²) based seven-coordinated cobalt(II) complexes, [Co(Lⁿ)X₂] (n = 1 and X = DMF for (1); n = 2 and X = H₂O for (2)); [Co(H₂Lⁿ)Y₂] (n = 1 or 2; Y = N₃^- or NCS^-), has been synthesized and characterized by using spectroscopic techniques. Single crystal X-ray study of [Co(L¹)(DMF)₂] (1) complex exhibits pentagonal-bipyramidal coordination geometry where the pentadentate N₃O₂ ligand in the equatorial plane of the bipyramid and two dimethylformamide molecules in the axial area. Interaction of the cobalt(II) complexes with CT DNA has been investigated by absorption titration method and viscosity measurements which reveal that the cobalt(II) complexes could bind with CT DNA through intercalation. Cleavage activity of the complexes (1) and (2) with pBR 322 plasmid DNA was evaluated by agarose gel electrophoresis demonstrating that the ability of the complexes to cleave the pBR 322 plasmid DNA via oxidative pathway, possibly due to the involvement of a diffusible hydroxyl radical mechanism in presence and absence of an oxidative agent. The nuclease activity of the Co(II) complexes has strong dependence on the concentration of complex and reaction time, both in presence and absence of hydrogen peroxide.

Full text of DOI:10.1016/j.ica.2015.03.040

Accepted Manuscript
Seven coordinated cobalt(II) complexes with 2,6-diacetylpyridine bis(4-acyl-
hydrazone) ligands: Synthesis, characterization, DNA-binding and nuclease
activity
Cansu Gökçe, Nefise Dilek, Ramazan Gup
PII:
S0020-1693(15)00189-9
http://dx.doi.org/10.1016/j.ica.2015.03.040
ICA 16494
DOI:
Reference:
Inorganica Chimica Acta
To appear in:
Received Date:
Revised Date:
Accepted Date:
5 December 2014
24 March 2015
28 March 2015
Please cite this article as: C. Gökçe, N. Dilek, R. Gup, Seven coordinated cobalt(II) complexes with 2,6-
diacetylpyridine bis(4-acylhydrazone) ligands: Synthesis, characterization, DNA-binding and nuclease activity,
Inorganica Chimica Acta (2015), doi: http://dx.doi.org/10.1016/j.ica.2015.03.040
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Seven coordinated cobalt(II) complexes with 2,6-diacetylpyridine bis(4-
acylhydrazone) ligands: Synthesis, characterization, DNA-binding and nuclease
activity
Cansu Gökçea, Nefise Dilekb and Ramazan Gupa*
aDepartment of Chemistry, Science Faculty, Mugla Sıtkı Koçman University, 48100,
Mugla, Turkey
bDepartment of Physics, Arts and Sciences Faculty, Aksaray University, 68100,
Aksaray, Turkey
ABSTRACT
A new series of pentadentate 2,6-diacetylpyridine bis(4-acylhydrazone)s (H2L1 and
H2L2) based seven-coordinated cobalt(II) complexes, [Co(Ln)X2] (n= 1 and X= DMF
-
for (1); n= 2 and X= H2O for (2)); [Co(H2Ln)Y2] (n= 1 or 2; Y= N3 or NCS-), has been
synthesized and characterized by using spectroscopic techniques. Single crystal X-ray
study of [Co(L1)(DMF)2] (1) complex exhibits pentagonal-bipyramidal coordination
geometry where the pentadentate N3O2 ligand in the equatorial plane of the bipyramid
and two dimethylformamide molecules in the axial area. Interaction of the cobalt(II)
complexes with CT DNA has been investigated by absorption titration method and
viscosity measurements which reveal that the cobalt(II) complexes could bind with CT
DNA through intercalation. Cleavage activity of the complexes (1) and (2) with pBR
322 plasmid DNA was evaluated by agarose gel electrophoresis demonstrating that the
ability of the complexes to cleave the pBR 322 plasmid DNA via oxidative pathway,
possibly due to the involvement of a diffusible hydroxyl radical mechanism in presence
and absence of an oxidative agent. The nuclease activity of the Co(II) complexes has
strong dependence on the concentration of complex and reaction time, both in presence
and absence of hydrogen peroxide.
Keywords: 2,6-Diacetylpyridine; acylhydrazone; cobalt(II) complex; DNA binding;
nuclease activity
1. Introduction
Corresponding author. Tel.: +90 252 2111496; fax: +90 252 2111472.
E-mail address: rgup@mu.edu.tr (R. Gup)

Transition metal complexes have a huge impact on biological applications in
bioinorganic chemistry due to their coordination behavior and importance in catalysis
[1-6]. The interaction of transition metal complexes with DNA has been intensively
studied to develop newer materials for application in biotechnology and medicine in
recent years. Generally, DNA is the essential target molecule for most disease therapies
such as anticancer and antiviral. Any disorder in gene expression may cause diseases
and plays a secondary role in the outcome and severity of human diseases. Transition
metal complexes can interact with DNA through the covalent or non-covalent modes
such as groove binding, intercalation and external static electronic effects among them
the most important is intercalation [7,8]. Investigations have resulted in the synthesis of
many new transition metal based complexes, which bind to DNA through non-covalent
interactions [8-12]. Cleavage of DNA may be considered as an enzymatic reaction
which comprises various biological processes as well as biotechnical manipulation of
genetic material. Thus, there is an increasing focus on the interaction study of small
molecules with DNA during the last decades. A more complete understanding of DNA
binding is necessary to design a new drug.
Geometry of the coordination compounds depending on the metal ion type and
different functional groups in the ligands is primarily responsible for the affinity of the
metal complexes to DNA. Transition metal complexes with tunable coordination
environments offer a great scope for the design of species that are suitable for DNA
binding and cleavage activities. Although many cobalt complexes with different
geometries have been synthesized, characterized and their interactions with DNA have
been studied extensively [8,9,12-18], there is no report related to DNA binding and
DNA cleavage studies of seven coordinated cobalt complexes in literature, to the best of
our knowledge. A few heptacoordinate Co(II) complexes based on bis(acylhydrazone)
ligands have been synthesized and characterized. Giordano et al., design and
synthesized a seven-coordinated Co(II) complex [Co(H2DAPBH)(H2O)(NO3)](NO3)
[H2DAPBH= 2,6-diacetylpyridine bis-(benzoylhydrazone)] [19] and Ruamps and co-
workers [20] investigated the nature and magnitude of the magnetic anisotropy of this
complex by a combination of experiment and ab initio calculations. On the other hand,
many seven coordinated metal complexes based on 2,6-diaceylpyridine bis(hydrazone)
ligands have been synthesized and characterized [21-27], yet only a few of them have
2

reported on their pharmacological properties and RNA interactions. So here in, we
report the synthesis and characterization and DNA interaction of the new seven
coordinated Co(II) complexes of two 2,6-diacetylpyridine pentadentate
bis(acylhydrazone) ligands bearing carboxylic acid ester groups.
2. Results and discussion
The new pentadentate hydrazone Schiff base ligands containing carboxylic ester
groups, 2,6-diacetylpyridine bis(4-ethyloxyacetatebenzoylhdrazone) (H2L1) and 2,6-
diacetylpyridine bis(4-ethyloxybutyratebenzoylhdrazone) (H2L2), were easily
prepared by the reaction of 2,6-diacetylpyridine bis(4-hydroxybenzoylhydrazone)
with ethyl bromoacetate and ethyl 4-bromobutyrate in the presence of dry K2CO3
and catalytic amount of KI. The cobalt(II) complexes were synthesized by the
reaction of the synthesized Schiff base hydrazone ligands with cobalt(II) acetate and
unidentated ion in the ratio of 1:1:2. The nature of bonding and geometry of the
Co(II) complexes as well as Schiff base hydrazones were deduced from elemental
analysis, magnetic susceptibility measurements, various spectroscopies (IR, UV-
Vis, 1H NMR, 13C NMR) and single crystal X ray diffraction techniques.
2.1. NMR spectra
1
The main H NMR signals for each of the H2L1 and H2L2 ligands in DMSO-d6 are
given in the experimental section. Formations of the H2L1 and H2L2 are confirmed by
the absence of the OH proton signal at 10.16 ppm assigned to the starting material 2,6-
13
diacetylpyridine bis(4-hydroxybenzoylhydrazone). In the C NMR spectra of ligands,
the signals for the carbonyl carbons of carboxylic ester and amide groups are observed
at 170.4 and 161.7 for H2L2 and 168.4 and 154.2 ppm for H2L1. The characteristic
chemical shifts of azomethine groups appear at 142.5 and 142.1 ppm. These
assignments are in good agreement with those previously reported for similar
compounds [27-30].
2.2. IR spectroscopy
The broad vibration band of ν(O−H), in the IR spectra of the starting material,
disappears and a new strong band is observed at 1758 and 1731 cm-1 for H2L1 and H2L2,
3

respectively, in the IR spectrum of the hydrazone ligands due to the stretching vibration
of the ester carbonyl, which is also characteristic for carboxylic esters, indicating that
condensation takes place [11,28-31]. In the IR spectra of the Co(II) complexes 1 and 2,
the amide I band disappears and a new band is observed at 1603 cm-1 probably due to
>C=N-N=C< stretching vibration indicating transformation of the carbonyl group to its
enolic form through keto-enol tautomerism and subsequent coordination of the enolic
oxygen to cobalt(II) ion after deprotonation. The IR spectra of the other cobalt(II)
complexes show sharp stretching vibrations peaks between 3383-3421 cm-1, 1627-1645
-1
-1
−H), amide I and imine groups, respectively, indicating
cm 1601-1604 cm due to ν(N
the coordination in the keto form. In addition, the bands due to the carbonyl of the
carboxylic ester vibrations remain unaltered, suggesting non-involvement of these
groups in the complex formation [28-31].
On the basis of IR spectral data we can conclude that in the case of the complexes 1
and 2 the bis(aroylhydrazone) ligands act as di anionic O,N,N’,N,O-pentadentate
ligands and the sixth and seventh positions are occupied by two dimethylformamide and
water molecules, respectively. On the other hand, they act as neutral O,N,N’,N,O-
-
pentadentate ligands and the axial positions are occupied by SCN- or N3 anions with
pentagonal-bipyramidal geometry in the other cobalt(II) complexes.
2.3. Electronic absorption spectra
In the UV-vis spectra of the bis(hydrazone) ligands two bands are observed at ~214
nm and ~312 nm. The latter is assignable to the n→π* transition. The cobalt(II)
complexes in DMF exhibit two bands around 270 and 350 nm, and a shoulder around at
416 nm. By comparing the electronic absorption spectra of the free hydrazone ligands
and their Co(II) complexes, it is observed that the maxima bands of the free ligands
exhibit bathochromic shifts. The first band observed in UV-vis spectra of the cobalt(II)
complexes is assignable to the aromatic ring transition π→π*. The other bands can be
assigned the n→π* type electronic transitions.
The observed magnetic moments values of the cobalt(II) complexes range from 4.21
to 4.31 BM. These µeff values lie in the range corresponding to three unpaired electrons
for pentagonal bipyramidal geometry (S = 3/2) around cobalt(II), d7 complexes.
2.4. Description of Crystal structure of [Co(L1)(DMF)2] (1)
4

The crystal structure is shown in Fig. 1 with atom-numbering scheme. Basic crystal
data, description of the diffraction experiment and details of the structure refinement are
given in Table 1. Selected bond distances and angels are presented in Table 2. The
cobalt(II) complex 1 crystallizes in the Triclinic P-1 space group and has a
crystallographic symmetry of two-fold axis. In the asymmetric unit, there are two DMF
(dimethylformamide) molecules. The central Co(II) atom is seven-coordinated with
N5O2 coordination environment and has a pentagonal bipyramid coordination geometry.
The H2L1 acts as a pentadentate dianionic ligand which is bound to the Co(II) ion
through three nitrogen atoms [N(2), N(3) and N(4)] and two oxygen atoms [O(4) and
O(5)] defining the equatorial coordination plane. The pentagonal-bipyramidal
coordination geometry around cobalt atom is completed by the oxygen atoms [O(9) and
O(10)] of two dimethylformamide molecules which are bound to Co(II) in axial
positions. The average Co-O bond length 2.191 (2) Å. The Co-N bond lengths range
from 2.157 (2) to 2.230 (2) Å. The Co–N(2) bond length is slightly smaller than those of
the other two Co–N bonds.
The central angle of a regular pentagon is 72º, whereas the N4–Co–N2, N2–Co–N3,
O5–Co–N4 and N3–Co–N4 angles in the titled Co(II) complex are 71.98(6)º, 70.99(7)º,
69.99(6)º and 69.59(6)º, respectively. On the other hand, the regular angle between axial
and equatorial positions is 90º while the observed angles of the titled Co(II) complexes
are between 85.27(6)º and 93.19(6)º. The bond angle of the O9–Co–O10 in the axial
position is 177.04(6)º. These observations indicate that the complex has a slightly
distorted pentagonal bipyramid geometry around cobalt(II). The all chelate rings of
molecule are essentially planar. The other bond lengths and angles in the molecule are
within expected ranges, and similar to the other studies [19,20].
Insert Table 1
The H atoms were positioned geometrically, with C–H = 0.93 Å (aromatic) and
constrained to ride on their parent atoms, with Uiso(H) = 1.2Ueq(C). Also, the C-bound
H-atoms were positioned geometrically with C—H = 0.97 Å and 0.96 Å for methylene
and methyl H-atoms, and constrained to ride on their parent atoms, with Uiso(H) =
1.2Ueq(Cmethylene) and Uiso(H) = 1.5Ueq (Cmethyl).
Insert Table 2
5

As can be seen from the packing diagram (Fig. S1), inter-molecular and intra-
molecular C—H…O and C–H...N hydrogen bonds (Table S2) link the molecules and
these hydrogen bonds may be effective in the stabilization of the crystal structure. In
these interactions, the C32, C33, C34 and C35 atoms act as donor. Both of the DMF
molecules form hydrogen bonds with the basic molecule.
2.5. Binding studies
2.5.1. Electronic absorption titrations
Fig. 2.
The interactions of cobalt(II) complexes with CT DNA were investigated by UV-Vis
absorption titrations [32-34]. The electronic absorption spectra of the cobalt(II)
complexes in the absence and in the increasing concentrations of CT-DNA are given in
the Fig. 2 and Figs. S2-S6. The binding of the Co(II) complexes to DNA helices was
characterized by following the changes in the absorbance and shift in wavelength on
each addition of the increasing concentration of DNA solution to the Co(II) complex
solution. Upon incremental addition of CT DNA from 0 to 80 µM, the maximum
absorbance band of the cobalt(II) complexes at ~350 nm exhibits a significant
hypochromism with a moderate blue shift of ~2 nm which indicates the interactions
between DNA and the Co(II) complexes. The complex 1 shows the biggest
hypochromism (26.29%) and hypsochromic shift (4 nm) among the all titled cobalt(II)
complexes. With increasing concentration of DNA, the absorption of the complex 1 at
348 nm is almost disappeared a new shoulder appears at ~323 nm which affords an
isobestic point at 331 nm. These spectral changes reveal that all titled Co(II) complexes
interact with CT DNA most likely through an interaction mode that involves π-π
stacking interaction between the aromatic chromophore and base pairs of DNA.
In order to compare the DNA binding affinity of these complexes quantitatively,
their binding constants, Kb, were determined from the plot of [DNA] ⁄ (εa – εf) versus
[DNA] (Table 3). The binding constant values for the cobalt(II) complexes 1, 2, 3, 4, 5
and 6 were found to be 3.33 x105 M-1, 2.33 x105 M-1, 2.50 x105 M-1, 1.67 x105 M-1, 1.00
x105 M-1and 2.00 x105 M-1, respectively. The observed values of Kb reveales that the
complex 1 binds more strongly to CT DNA then the other cobalt complexes via an
6

intercalative mode. These observations are quite smiliar to the Kb values of previously
reported cobalt(II) complexes [12,35,36].
Insert Table 3
2.5.2. Viscosity measurements.
The binding modes of the cobalt(II) complexes to DNA were further confirmed via
viscosity measurement carrying out by keeping [DNA]=0.5 mM and varying the
concentrations of Co(II) complexes, DAPI or EB [28,37,38]. The results are shown in
Fig. 3 and S7 – S11 for the complexes 1, 2, 3, 4, 5 and 6, respectively. In this study, we
have used the EB and DAPI as references. As can be seen from the Fig. 3, ethidium
bromide (EB), being a well-known DNA intercalator between DNA base pairs and thus
lengthening the DNA double helix, increases the relative viscosity of DNA sharply
whereas the viscosity of double strand DNA remains almost unchanged in the case of
DAPI, minor groove binding agent. An increase in the relative viscosity of CT DNA
upon adding increasing amounts of cobalt(II) complexes also suggests the intercalative
mode of binding.
Fig. 3.
2.6. Nuclease activity of the cobalt(II) complexes
In order to assess the nuclease activity of DNA as results of strong binding of
complexes 1 and 2, agarose gel electrophoresis was performed using supercoiled
pBR322 plasmid DNA as a substrate in a medium of 5 mM Tris-HCl/50 mM NaCl
buffer at pH 7.2 [38-43]. The cleavage experiments were carried out in the presence and
absence of activating agent, H2O2, under different concentration of complex (25-200
µM) and incubation time (1 h to 6 h) at 37 ºC, and the results are shown in Figs. 4 and 5
for 1 and Figs. S12 and S13 for 2.
Fig. 4.
It is observed that both complexes 1 and 2 exhibit considerable nuclease activity and
their DNA cleavage abilities are almost similar under both conditions. Both complexes
convert the supercoiled DNA to nicked and linear forms suggesting double strand DNA
cleavage. The amount of form II and III increases gradually whereas the intensity of
7

form I DNA diminishes with increasing concentration of the complexes. The results
illustrate that the Co(II) complexes can effectively cleavage DNA both in the presence
and absence an oxidative agent, and the cleavage efficiency of the complexes gradually
increases with the increase in concentration of the complexes (Figs. 4a and 5a for 1;
Figs. S12a and S13a for 2). The time course of pBR 322 DNA cleavage mediated by the
cobalt(II) complexes (100 µM) was also carried out with agarose gel electrophoresis in
the buffer at 37 C in presence and absence of oxidative agent. As shown in Figs. 4b, 5b,
S12b and S13b, when the incubation time increases, the intensity of circular supercoiled
form decreases while those of forms II and III increases gradually. In the case of the
oxidative cleavage, from I is almost disappeared after 6 h incubation (lanes 6). The
results illustrate that the Co(II) complexes cleavage DNA both in the presence and
absence of an oxidative agent, and the cleavage of DNA by the cobalt(II) complexes is
dependent on the reaction time. The results also indicate that the chemical nuclease
activity of the complex 1 is slightly higher than that of the complex 2 probably due to
the higher DNA binding affinity of 1.
Fig. 5.
To elucidate the mechanism involved in the DNA cleavage by complexes 1 and 2,
the reactions were carried out in the presence of superoxide dismutase as superoxide
-
anion radicals (•O2 ) scavenger, NaN3 as singlet oxygen (1O2) quencher and DMSO as
hydroxyl radical (OH•) scavenger in the presence and absence of hydrogen peroxide. As
shown in Figs. 4c, 5c, S12c, and 13c, lanes 2, the addition of DMSO significantly
inhibits the cleavage activity of the cobalt(II) complexes both in the presence and
absence of H2O2 suggesting that the freely diffusible hydroxyl radical is involved in the
DNA cleavage reaction of the Co(II) complexes 1 and 2. It may be concluded from
these results that the cobalt(II) complexes 1 and 2 may cleavage the DNA probably
through oxidative mechanism.
In order to probe the potential interacting site of the cobalt(II) complexes with
plasmid pBR322 DNA, the effects of groove binding drugs on the strand scission were
also determined by using 4,6-diamidino-2-phenylindole (DAPI) and methyl green,
which are known to bind to DNA at minor groove and major groove, respectively
[44,45]. Prior to the addition of the complex, no apparent inhibition of DNA damage is
observed in presence of both DAPI and methyl green (Figs. 4c and 5c, lanes 5 and 6)
8

either in presence or absence of H2O2 suggesting that the titled cobalt(II) complexes do
not interact with the CT DNA by groove binding mode.
3. Conclusions
We describe here six seven coordinated cobalt(II) complexes of two pentadentate
ligands, 2,6-diacetylpyridine bis(acylhydrazone) bearing ester groups. The single crystal
structure of the Co(II) complex 1 has revealed a distorted pentagonal-bipyramidal
geometry. The equatorial plane of the bipyramid is occupied by the pentadentate N3O2
2,6-diacetylpyridine bis(ethyl 2-(4-hydrazinecarbonyl)phenoxy)acetate) ligand while
two dimethylformamide molecules occupy the axial position of the complex. The
binding behaviors of the complexes with CT DNA were investigated by using
absorption spectroscopy. The results indicate that the complexes could bind to CT DNA
via intercalation. Further, viscosity study offers further support for the intercalative
mode of binding of these cobalt(II) complexes. The cobalt(II) complexes 1 and 2 exhibit
efficient nuclease activity in the presence and absence of hydrogen peroxide which has
strong dependence on the concentration of complex as well as the reaction time. The
hydroxyl radical scavenger effectively inhibits DNA cleavage mediated by the Co(II)
complexes 1 and 2 either in the presence absence of H2O2. These observations seem to
suggest that the cobalt(II) complexes promote cleavage activity of pBR 322 plasmid
DNA by oxidative cleavage mechanism. However, further studies warrant elucidating
the detailed mechanisms of the Co(II) complex-mediated DNA cleavage. Results
obtained from this study would be useful in the design of more effective and useful
seven-coordinated transition metal complexes for DNA interactions.
4. Experimental Section
4.1. Material and methods
All the reagents and solvents were of reagent grade quality and were purchased from
commercial suppliers. 4-Hydroxybenzohydrazide was synthesized by refluxing ethyl 4-
hydroxybenzoate with excess hydrazine hydrate. Calf thymus DNA (CT-DNA) was
1
purchased from Sigma- Aldrich. pBR 322 DNA was purchased from Fermantas. H and
13C NMR spectra were recorded on a Bruker 400 MHz spectrometer in DMSO-d6 with
9

TMS as the internal standard. IR spectra were recorded on pure solid samples with a
Thermo-Scientific, Nicolet iS10-ATR. The electronic spectra of the compounds were
recorded on a PG Instruments T80+ UV/Vis Spectrophotometer. Carbon, hydrogen and
nitrogen analyses were carried out on a LECO 932 CHNS analyzer and cobalt content
was determined by atomic absorption spectroscopy using the DV 2000 Perkin Elmer
ICP-AES. Room temperature magnetic susceptibility measurements were carried out on
powdered samples using a Sherwood Scientific MK1 Model Gouy Magnetic
Susceptibility Balance.
The
preparation of 2,6-diacetylpyridine
bis(4-
hydroxybenzoylhydrazone) has been described previously [27].
4.2. Synthesis of 2,6-diacetylpyridine bis(4-ethyloxyacetatebenzoylhdrazone) (H2L1)
Ethyl bromoacetate (2 mmol, 0.334 g) was added to a mixture of 2,6-
diacetylpyridine bis(4-hydroxybenzoylhydrazone) (1 mmol, 0.431 g) and dry K2CO3 (2
mmol, 0.276 g) in 25 mL acetone with catalytic amount of KI. The reaction mixture was
refluxed with stirring for 24 hours and poured to ice water. The white precipitate formed
was filtered and washed with water and finally recrystallized from methanol. Yield 68
%; Mp 107 °C; UV (DMF, nm) 214, 312, IR (ATR, cm−1) 3282 (NH), 2998-2911
(CH)aliphatic, 1758 (C=O)ester, 1651 (C=O)amide, 1604 (C=N), 1385 (C-N), 1256 and 1176
(C-O-C); 1H NMR (DMSO-d6, ppm) δ 1.24 (t, 6H, CH3), 2.55 (s, 3H, N=C-CH3), 4.21
(q, 4H, OCH2CH3), 4.92 (s, 4H, Ar-OCH2) and 4.87 (s, 2H, Ar-OCH2), 7.08 (d, 4H,
ArH), 7.91, (d, 4H, ArH), 8.10 (m, 3H, ArH), 10.80 (s, 2H, NH); 13C NMR (DMSO-d6,
ppm) 168.4 (C=O)ester, 160.2 (C=O)amide, 154.2 (C-O), 142.1 (C=N), 137.1, 130.7, 130.2,
129.9, 126.6, 120.4, 114.1 (Ar-C), 64.6 (COOCH2) and 60.7 (OCH2), 14.6 (CH3-C=N),
12.3 (CH3CH2). Analysis (%Calculated/found) for C31H33N5O8; C: 61.68/61.90, H:
5.51/5.40, N: 11.60/11.37.
4.3. Synthesis of 2,6-diacetylpyridine bis(4-ethyloxybutyratebenzoylhdrazone) (H2L2)
Ethyl 4-bromobutyrate (2 mmol, 0.429 g) was added to a suspension of 2,6-
diacetylpyridine bis(4-hydroxybenzoylhydrazone) (1 mmol, 0.431 g) and dry K2CO3 (2
mmol, 0.276 g) in DMF (10 mL) with catalytic amount of KI. The reaction mixture was
refluxed with stirring for 4 hours and poured to 200 mL of ice water. The white
precipitate formed was filtered and washed with water and finally recrystallized from
10

ethanol. Yield 70 %; Mp 165 °C; UV (MeOH, nm) 216, 295 sh, 316, IR (ATR, cm−1)
3273 (NH), 2977-2922 (CH)aliphatic, 1731 (C=O)ester, 1654 (C=O)amide, 1606 (C=N), 1372
1
(C-N), 1247 and 1172 (C-O-C); H NMR (DMSO-d6, ppm) δ 1.20 (t, 6H, CH3), 2.02
(qui, 4H, CH2CH2CH2), 2.55 (s, 6H, N=C-CH3), 2.49 (4H, COCH2), 4.10 (m, 8H,
OCH2), 7.05 (d, 4H, ArH), 7.91, (d, 4H, ArH), 8.10 (m, 3H, ArH), 10.77 (s, 2H, NH);
13C NMR (DMSO-d6, ppm) 170.4 (C=O)ester, 161.7 (C=O)amide, 152.6 (C-O), 142.6
(C=N), 137.7, 134.9, 130.7, 126.6, 129.9, 124.6, 123.6, 114.5 (Ar-C), 68.2, 61.4, 30.3,
24.1, 14.1, 12.6 (CAliphatic). Analysis (%Calculated/found) for C31H33N5O8; C:
63.72/63.89, H: 6.26/6.70, N: 10.62/10.78
4.4. Synthesis of Co(II) complexes
4.4.1. [Co(Ln)X2] (n=1, X= DMF for 1; n=2, X= H2O for 2)
A solution of (CH3COO)2Co·4H2O (0.249 g, 1 mmol) in MeOH (10 ml) was added
by dropwise to suspension of the ligand (1 mmol) in 50 ml MeOH. The reaction mixture
was refluxed for 3 h. The precipitated orange complex was filtered off, washed with
water and methanol. In the case of the complex 1, the crystals suitable for X-ray
diffraction were obtained upon diffusion of the ethyl ether into the DMF solution.
For [Co(L1)(DMF)2] (1)
Yield: 81%; m.p.: 170 ºC. µeff = 4.22 B.M.; UV (DMF, nm) 268, 352, 411 (sh); FT-
−1
−N=C), 1262 s (C−O).
IR (ATR, cm ) 1763 s (C=O), 1603 m (C=N
Analysis
(%Calculated/found) for C37H45CoN7O10; C: 55.09/55.20, H: 5.62/5.50, N: 12.15/11.95,
Co: 7.31/7.25.
For [Co(L2)(H2O)2] (2)
Yield: 81%; m.p.: 190 ºC. µeff = 4.31 B.M.; UV (DMF, nm) 270, 350, 400 (sh); FT-
−1
−N=C), 1246 s (C−O).
IR (ATR, cm ) 3383 b (O–H), 1728 s (C=O), 1603 (C=N
Analysis (%Calculated/found) for C35H43CoN5O10 C: 55.85/55.60, H: 5.76/5.44, N:
9.30/9.06, Co: 7.83/7.39.
-
4.4.2. [Co(H2Ln)Y2] (n=1 or 2; Y= N3 (3 and 4) or NCS- (5 and 6)
11

A solution of (CH3COO)2Co·4H2O (0.249 g, 1 mmol) in MeOH (10 ml) was added
by dropwise to suspension of the ligand (1 mmol) in 50 ml MeOH. After the mixture
was refluxed for 0.5 h, an aqueous solution of KSCN (0.194 g, 2 mmol in 5 ml) or NaN3
(0.130 g, 2 mmol) was added, and the resulting mixture was refluxed for further 3 h.
The precipitate was filtered off, washed with methanol and diethyl ether several times,
and dried in vacuum.
For [Co(H2L1)(N3)2] (3)
Red complex; yield: 74%; m.p.: 310 ºC. µeff = 4.25 B.M.; UV (DMF, nm) 272, 350,
422 (sh); FT-IR (ATR, cm−1) 3421 w (N-H), 2046 s and 1297 w (N=N=N), 1751 s and
1638 m (C=O), 1601 m (C=N), 1265 s (C−O). Analysis (%Calculated/found) for
C31H33CoN11O8; C: 49.87/50.05, H: 4.46/4.68, N: 20.64/20.21, Co: 7.89/7.66.
For [Co(H2L2)(N3)2] (4)
Brown complex; yield: 77%; m.p.: <350 ºC. µeff = 4.20 B.M.; UV (DMF, nm) 270,
352, 402 (sh); FT-IR (ATR, cm−1), 3383 w (N-H), 2034 s and 1273 s (N=N=N), 1724
−O).
and 1627 s (C=O), 1604 m (C=N), 1244 s (C
Analysis (%Calculated/found) for
C35H41CoN11O8; C: 52.37/52.54, H: 5.15/5.23, N: 19.19/19.36, Co: 7.34/7.49.
For [Co(H2L1)(NCS)2] (5)
Red complex; yield: 79%; m.p.: 230 ºC. µeff = 4.25 B.M.; UV (DMF, nm) 270, 348,
416 (sh); FT-IR (ATR, cm−1) 3383 w (N–H), 2050 m and 902 w (S=C=N), 1751 s and
−O).
1640 m (C=O), 1603 (C=N), 1242 s C
Analysis (%Calculated/found) for
C33H33CoN7O8S2; C: 50.90/50.37, H: 4.27/4.31, N: 12.59/12.40, S: 8.23/8.62, Co:
7.57/7.49.
For [Co(H2L2)(NCS)2] (6)
Red complex; yield: 75%; m.p.: 315 ºC. µeff = 4.21 B.M.; UV (DMF, nm) 268, 350,
406 (sh); FT-IR (ATR, cm−1) 3440 w (N–H), 2078 s and 940 w (S=C=N), 1721 s and
−O).
1645 m (C=O), 1602 (C=N), 1252 s C
Analysis (%Calculated/found) for
C37H41CoN7O8S2; C: 53.23/53.41, H: 4.95/4.76, N: 11.74/11.38, S: 7.68/7.77, Co:
7.06/7.21.
12

4.5. X-ray Diffraction Study
Crystallographic data were recorded on a Bruker Smart Breeze CCD area-detector
diffractometer using MoKα radiation (λ=0.71073 Å) at T=296 (2) K [46]. Absorption
corrections by multi-scan were applied [47] Cell refinement was carried out using
Bruker SAINT and data was reduced by using Bruker SAINT [48]. The structure was
solved using SHELXS97 [47] and refined using SHELXL2013 [48] by full-matrix least-
squares on F2 against ALL reflections. The weighted R-factor wR and goodness of fit S
are based on F2. The threshold expression of F2 > 2sigma(F2) is used only for
calculating R-factors. All estimated standard deviations (e.s.d.’s) are calculated using
the full covariance matrix. The cell e.s.d.’s are taken into account individually in the
estimation of e.s.d.’s in distances, angles, and torsion angles; correlations between
e.s.d.’s in cell parameters are only used when they are defined by crystal symmetry.
Molecular graphics were drawn ORTEP-3 [49], PLATON [50] and the material for
publication prepared using WinGX [51]. All non-hydrogen atoms were refined
anisotropically and hydrogen atoms were added according to the theoretical model. The
fractional atomic coordinates are given in Table S1, supporting information.
4.6. DNA Binding
4.6.1. Electronic absorption titrations
All the experiments involving the interaction of the complexes with CT-DNA were
carried out in water buffer containing 5 mM tris [tris(hydroxymethyl)aminomethane]
and 50 mM NaCl, and adjusted to pH 7.3 with HCl. The solution of CT-DNA in the
buffer gave a ratio of UV absorbance of 1.8 –1.9:1 at 260 and 280 nm, indicating that
the CT-DNA was sufficiently free of protein [52]. The CT-DNA concentration per
nucleotide was determined spectrophotometrically by employing an extinction
coefficient of 6600 M-1 cm-1 at 260 nm [53]. An appropriate amount of the cobalt
complex was dissolved in a solvent mixture of 1% DMF and 99% tris–HCl buffer.
Absorption titration experiments were performed by maintaining the metal complex
concentration as constant while gradually increasing the concentration of the CT-DNA
within 0-80 µM.
13

4.6.2. Viscosity measurements
Viscosity experiments were carried out using an Ubbelodhe viscometer at room
temperature. The viscosity of CT-DNA solution (25 µM) was measured in the absence
and presence of increasing amounts of the complex (6,25-50 µM) in tris-HCl buffer (10
mM tris–HCl-NaCl; pH=7.6) containing %5 DMF solution. Flow time was measured
three times with a digital stopwatch. Viscosity values were presented as (η/η0)1/3 versus
concentrations of [complex]/[DNA] [28,38] where η was the viscosity value for DNA in
presence of the cobalt(II) complex and η0 was the viscosity value of CT-DNA alone.
4.7. Chemical nuclease activity
pBR 322 plasmid DNA was used for all cleavage activities [28,38,39,43]. In a
typical experiment, 2 µL plasmid DNA (0.50 µg/µL) was mixed with different
concentration of the cobalt(II) complex (25, 50, 75, 100 and 200 µM) dissolved in DMF
to determine optimum activation concentration. In the case of oxidative cleavage, 5 µL
H2O2 (5 mM) was added to mixture to oxidize the reactant. Finally the reaction mixture
was diluted with the Tris buffer (100 mM Tris, pH: 8) to a total volume of 30 µL. After
that reaction mixtures were incubated at 37 ºC for two hours. Samples (20 µL) were
then loaded with 4 µL loading dye (0.25% bromophenol blue, 0.25% xylene cyanol,
30% glycerol, 10 mmol EDTA) on a %1 agarose gel containing 1 µg/mL of EtBr. The
gel was run at 100 V for 3 h in TBE buffer and photographed under UV light. To test
for the presence of reactive oxygen species generated during strand scission, reactive
oxygen intermediate scavengers, that is, SOD, DMSO and NaN3 were added alternately
to the reaction mixture and the samples were treated as described above.
Acknowledgements
This work was funded by the Scientific and Technological Research Council of
Turkey (TÜBİTAK, TBAG-112T315).
Appendix A. Supplementary data
X-ray crystallographic files of the cobalt(II) complex (1) are available. These data
can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from
the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033; email:
14

deposit@ccdc.cam.ac.uk). Supplementary data associated with this article can be found,
in the online version.
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17

Figure Captions
Fig. 1. An ORTEP drawing of molecular structure with the crystallographic numbering
scheme. Thermal ellipsoids are drawn at % 30 probability levels.
Fig. 2. Absorption spectra of the complexe (1) with increasing concentration of CT-
DNA. [Complex] = 25 µM, [DNA] = 0–80 µM.
Fig. 3. Effect of increasing amounts of the cobalt(II) complex (1), DAPI and EB on the
relative viscosity of calf thymus DNA at room temperature.
Fig. 4. (a) Agarose gel electrophoresis patters of plasmid pBR 322 DNA after 2 h
incubation with various concentrations of complex (1) in the presence of H2O2. Lane 1,
1 (200 µM) + DNA + H2O2; Lane 2, 1 (100 µM) + DNA + H2O2; Lane 3, 1 (75 µM) +
DNA + H2O2; Lane 4, 1 (50 µM) + DNA + H2O2; Lane 5, 1 (25 µM) + DNA + H2O2;
Lane 6, DNA control. (b) Reaction time dependence of the oxidative DNA cleavage of
complexes (1), 1 (100 µM). Lane 7, DNA control; the reaction time for lanes 1-6 is 1, 2,
3, 4, 5, 6h, respectively. (c) Oxidative plasmid pBR 322 DNA cleavage in the presence
of different scavengers and presence of different groove binding after 2 h incubation
with of complex (1). Lane 1, 1 (100 µM) + DNA + H2O2; Lane 2, 1 (100 µM) + DNA +
H2O2 + DMSO; Lane 3, 1 (100 µM) + DNA + H2O2 + SOD; Lane 4, 1 (100 µM) + DNA
H2O2 + NaN3; Lane 5, 1 (100 µM) + DNA + H2O2 +DAPI; Lane 6, 1 (100 µM) + DNA
+ H2O2 + methyl green; Lane 7, DNA control.
Fig. 5. (a) Agarose gel electrophoresis patters of plasmid pBR 322 DNA after 3 h
incubation with various concentrations of complexes (1) in the absence of H2O2. Lane 1,
1 (200 µM) + DNA; Lane 2, 1 (100 µM) + DNA; Lane 3, 1 (75 µM) + DNA; Lane 4, 1
(50 µM) + DNA; Lane 5, 1 (25 µM) + DNA; Lane 6, DNA control. (b) Reaction time
dependence of the hydrolytic DNA cleavage by the complexes (1), 1 (100 µM). Lane 7,
DNA control; the reaction time for lanes 1-6 is 1, 2, 3, 4, 5, 6h, respectively; (c)
Hydrolytic plasmid pBR 322 DNA cleavage in the presence of different scavengers and
presence of different groove binding after 3 h incubation with of complexes (1). Lane 1,
1 (75 µM) + DNA; Lane 2, 1 (75 µM) + DNA + DMSO; Lane 3, 1 (75 µM) + DNA +
SOD; Lane 4, 1 (75 µM) + DNA + NaN3; Lane 5, 1 (75 µM) + DNA + DAPI; Lane 6, 1
(75 µM) + DNA + methyl green; Lane 7, DNA control.
Fig. S1. A packing diagram for molecule, projected along a direction. Hydrogen bonds
are indicated by dashed lines.
18

Fig. S2. Absorption spectra of the complex (2) with increasing concentration of CT-
DNA. [Complex] = 25 µM, [DNA] = 0–80 µM.
Fig. S3. Absorption spectra of the complex (3) with increasing concentration of CT-
DNA. [Complex] = 25 µM, [DNA] = 0–80 µM.
Fig. S4. Absorption spectra of the complex (4) with increasing concentration of CT-
DNA. [Complex] = 25 µM, [DNA] =0–80 µM.
Fig. S5. Absorption spectra of the complex (5) with increasing concentration of CT-
DNA. [Complex] = 25 µM, [DNA] = 0–80 µM.
Fig. S6. Absorption spectra of the complex (6) with increasing concentration of CT-
DNA. [Complex] = 25 µM, [DNA] = 0–80 µM.
Fig. S7. Effect of increasing amounts of the cobalt(II) complex (2), DAPI and EB on
the relative viscosity of calf thymus DNA at room temperature.
Fig. S8. Effect of increasing amounts of the cobalt(II) complex (3), DAPI and EB on
the relative viscosity of calf thymus DNA at room temperature.
Fig. S9. Effect of increasing amounts of the cobalt(II) complex (4), DAPI and EB on
the relative viscosity of calf thymus DNA at room temperature.
Fig. S10. Effect of increasing amounts of the cobalt(II) complex (5), DAPI and EB on
the relative viscosity of calf thymus DNA at room temperature.
Fig. S11. Effect of increasing amounts of the cobalt(II) complex (6), DAPI and EB on
the relative viscosity of calf thymus DNA at room temperature.
Fig. S12. (a) Agarose gel electrophoresis patters of plasmid pBR 322 DNA after 2 h
incubation with various concentrations of complex (2) in the presence of H2O2. Lane 1,
2 (200 µM) + DNA + H2O2; Lane 2, 2 (100 µM) + DNA + H2O2; Lane 3, 2 (75 µM) +
DNA + H2O2; Lane 4, 2 (50 µM) + DNA + H2O2; Lane 5, 2 (25 µM) + DNA + H2O2;
Lane 6, DNA control. (b) Reaction time dependence of the oxidative DNA cleavage of
complexes (2), 2 (100 µM). Lane 7, DNA control; the reaction time for lanes 1-6 is 1, 2,
3, 4, 5, 6h, respectively. (c) Oxidative plasmid pBR 322 DNA cleavage in the presence
of different scavengers and presence of different groove binding after 2 h incubation
with of complex (2). Lane 1, 2 (100 µM) + DNA + H2O2; Lane 2, 2 (100 µM) + DNA +
H2O2 + DMSO; Lane 3, 2 (100 µM) + DNA + H2O2 + SOD; Lane 4, 2 (100 µM) + DNA
H2O2 + NaN3; Lane 5, 2 (100 µM) + DNA + H2O2 +DAPI; Lane 6, 2 (100 µM) + DNA
+ H2O2 + methyl green; Lane 7, DNA control.
19

Fig. S13. (a) Agarose gel electrophoresis patters of plasmid pBR 322 DNA after 3 h
incubation with various concentrations of complexes (2) in the absence of H2O2. Lane 1,
2 (200 µM) + DNA; Lane 2, 2 (100 µM) + DNA; Lane 3, 2 (75 µM) + DNA; Lane 4, 2
(50 µM) + DNA; Lane 5, 2 (25 µM) + DNA; Lane 6, DNA control. (b) Reaction time
dependence of the hydrolytic DNA cleavage by the complexes (2), 2 (100 µM). Lane 7,
DNA control; the reaction time for lanes 1-6 is 1, 2, 3, 4, 5, 6h, respectively; (c)
Hydrolytic plasmid pBR 322 DNA cleavage in the presence of different scavengers and
presence of different groove binding after 3 h incubation with of complexes (2). Lane 1,
2 (50 µM) + DNA; Lane 2, 2 (50 µM) + DNA + DMSO; Lane 3, 2 (50 µM) + DNA +
SOD; Lane 4, 2 (50 µM) + DNA + NaN3; Lane 5, 2 (50 µM) + DNA + DAPI; Lane 6, 2
(50 µM) + DNA + methyl green; Lane 7, DNA control.
20

Fig. 1.
21

Fig. 2.
Fig. 3.
22

Fig. 4.
Fig. 5.
23

Table 1
Crystallographic data and structural refinement for the cobalt(II) complex
Chemical Formula
Formula weight (amu)
Co[C31H31N5O8].2(C3H7NO)
806.73
Crystalform, color
Crystal size (mm)
Crystal system
Space group
prism, orange
0.590 x 0.240 x 0.140
Triclinic
P-1
a (Å)
b (Å)
c (Å)
α (°)
8.9694 (7)
14.6496 (11)
15.0420 (11)
90.208 (4)
92.544 (4)
92.799 (4)
1956.2 (3)
2
β (°)
γ (°)
V (Å3)
Z
Dx (g/cm3)
1.370
0.71073
0.590
λ(MoKα) Å
µ(MoKα) mm–1
T (K)
θmax
296(2)
26.372
1.36
θmin
H
K
-11---11
-18----18
-18----18
45920
L
Number of reflections measured
Number of independent reflections
Number of reflections [I >2σ(I)]
7978
6041
Number of parameters
505
R
Rw
0.0427
0.0978
S
1.037
2
1/[σ2(Fo2) + (0.1040P)2
Weighting scheme,
P = (Fo + 2Fc2)/3
0.050
0.299, -0.231
(∆/σ)max
(∆ρ)max, (∆ρ)min (eÅ-3)
Measurements
Bruker APEXII
Structure determination
Refinement
Treatment of hydrogen atoms
direct method (SHELXS-97)
full matrix l.s. (SHELXL-2013)
geometric calculation
24

Table 2
Selected bond lengths (Å), bond angles (°) and torsion angles (°) of the cobalt(II)
complex.
Bond lengths
Bond angles
Torsion angles
Co–O4
2.129(2)
2.154(1)
2.272(2)
2.209(2)
2.157(2)
2.203(2)
2.230(2)
1.374(2)
1.383(2)
O4–Co–O5
O4–Co–N2
O5–Co–N2
O4–Co–N3
O5–Co–N3
N2–Co–N3
O4–Co–O10
O5–Co–O10
N2–Co–O10
N3–Co–O10
O4–Co–N4
O5–Co–N4
N2–Co–N4
N3–Co–N4
O10–Co–N4
O4–Co–O9
O5–Co–O9
N2–Co–O9
N3–Co–O9
O10–Co–O9
N4–Co–O9
C11–O4–Co
C21–O5–Co
C5–O3–C4
77.44(5)
C35–O10–Co
C12–N2–N1
C12–N2–Co
N1–N2–Co
120.1(2)
118.4(2)
122.7(2)
118.9(1)
116.8(2)
116.3(2)
108.4(2)
116.4(2)
117.8(2)
118.1(2)
121.8(2)
119.0(1)
107.9(2)
120.5(2)
118.7(2)
120.7(1)
125.6(2)
124.7(2)
125.8(2)
124.0(2)
126.8(2)
109.2(2)
128.0(2)
Co–O5–C21–N5
5.9(3)
Co–O5
71.98(6)
149.42(6)
142.95(6)
139.57(6)
70.99(7)
88.51(6)
90.56(6)
88.89(6)
91.92(6)
147.41(6)
69.99(6)
140.57(7)
69.59(6)
92.92(6)
93.19(6)
92.17(6)
89.34(6)
85.27(6)
177.04(6)
86.96(6)
115.4(1)
117.2(1)
118.2(2)
Co–O5–C21–C22
O4–C11–C8–C9
N1–C11–C8–C7
Co–N2–C12–C14
C4–O3–C5–C10
C28–O6–C25–C26
C28–O6–C25–C24
O2–C3–C4–O3
-170.7(1)
4.9(3)
Co–O9
Co–O10
Co–N2
4.4(3)
C25–O6–C28
C32–O9–Co
C11–N1–N2
C29–O8–C30
C3–O1–C2
2.8(2)
Co–N3
-3.6(3)
-7.5(3)
171.4(2)
-5.2(3)
-2.6(3)
9.1(3)
Co–N4
N2–N1
N4–N5
C19–N4–N5
C19–N4–Co
N5–N4–Co
C18–N3–C14–C15
Co–N4–C19–C18
Co–N4–C19–C20
N4–C19–C18–N3
C20–C19–C18–N3
C20–C19–C18–C17
C30–O8–C29–O7
O6–C28–C29–O7
O6–C28–C29–O8
N3–C14–C15–C16
C12–C14–C15–C16
Co–O9–C32–N6
C33–N6–C32–O9
N3–C18–C17–C16
C3–O1–C2–C1
-167.7(2)
-4.2(3)
172.7(2)
-5.9(4)
-2.9(4)
6.3(4)
C21–N5–N4
C14–N3–C18
C14–N3–Co
C18–N3–Co
O5–C21–N5
O2–C3–O1
-173.0(2)
3.8(4)
O10–C35–N7
O7–C29–O8
O7–C29–C28
O8–C29–C28
O9–C32–N6
-173.6(2)
-167.1(2)
-3.5(5)
2.8(4)
97.5(3)
Note: Symmetry transformations: #-x, y, -z+1/2
25

Table 3
Effect of CT-DNA on the absorbance bands and binding constant of the complexes and
adducts
Comple
λ
Free
max (nm)
H (%)
Kb(M-1)
∆λ (nm)
x
1
2
3
4
5
6
Bound
352.0
350.0
350.0
352.0
348.0
350.0
348.0
4.0
4.0
2.0
2.0
2.0
2.0
26,29
8,99
3.33 x105
2.33 x105
2.50 x105
1.67 x105
1.00 x105
2.00 x105
346.0
348.0
350.0
346.0
348.0
13,89
10,13
11,11
11,79
26

The synthesis of a new series of seven-coordinated cobalt(II) complexes and their DNA
interaction are reported.
Seven coordinated cobalt(II) complexes with 2,6-diacetylpyridine bis(4-
acylhydrazone) ligands: Synthesis, characterization, DNA-binding and nuclease
activity
Cansu Gökçe, Nefise Dilek and Ramazan Gup
27

H3C
CH3
N
Y
N
N
Co
HN
NH
O
O
Y
O
R
O
R
O
O
R= -CH2- or -CH2CH2CH2-; Y= N3- or SCN-
O
O
CH3
CH3
A new series of pentadentate bis(4-acylhydrazone)s based seven-coordinated cobalt(II)
-
complexes, [Co(L)X2] (X= DMF, H2O) and [Co(H2L)Y2] (Y= N3 or NCS-), has been
synthesized and characterized. Single crystal X-ray study of [Co(L1)(DMF)2] reveals
that Co(II) complex has a pentagonal-bipyramidal coordination geometry. The cobalt(II)
complexes bind to DNA through intercalation, and they are able to cleavage DNA both
in the presence and absence of oxidant agent.
28

Highlights
• Six new seven-coordinated Co(II) complexes of pentadentate ligands have
synthesized.
• [Co(L1)(DMF)2] has been structurally characterized.
• The cobalt(II) complexes bind with CT DNA through intercalation.
• The Co(II) complexes cleavage the pBR322 plasmid DNA via oxidative pathway.
29